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In this post-genomic era, genome-wide functional analysis is indispensable. The recent development of RNA interference techniques has enabled researchers to easily analyze gene function even in non-model organisms. On the other hand, little progress has been made in the identification and functional analyses of cis-regulatory elements in non-model organisms. In order to develop experimental platform for identification and analyses of cis-regulatory elements in a non-model organism, in this case, the ladybird beetle, Harmonia axyridis, we established transgenic transposon-tagged lines using a novel composite vector. This vector enables the generation of two types of insertion products (jumpstarter and mutator). The jumpstarter portion carries a transposase gene, while the mutator segment carries a reporter gene for detecting enhancers. The full-composite element is flanked by functional termini (required for movement); however, the mutator region has an extra terminus making it possible for the mutator to remobilize on its own, thus leaving an immobile jumpstarter element behind. Each insertion type is stable on its own, but once crossed, jumpstarters can remobilize mutators. After crossing a jumpstarter and mutator line, all tested G2 females gave rise to at least one new insertion line in the next generation. This jumping rate is equivalent to the P-element-mediated jumpstarter method in Drosophila. These established transgenic lines will offer us the ideal experimental materials for the effective screening and identification of enhancers in this species. In addition, this jumpstarter method has the potential to be as effective in other non-model insect species and thus applicable to any organism.

Background: Knockdown resistance (kdr) has been identified as a main mechanism against pyrethroid insecticides in many arthropod pests including in the onion thrips, Thrips tabaci. To characterize and identify pyrethroid-resistance in onion thrips in Washington state, we conducted insecticide bioassays and sequenced a region of the voltage gated sodium channel gene from several different T. tabaci populations., Results: Field collected Thrips tabaci were found to have large variations in resistance to the pyrethroid insecticide lambda-cyhalothrin. We identified two single nucleotide substitutions in our analysis of a partial sequence of the T. tabaci voltage-gated sodium channel gene. One mutation resulted in the non-synonymous substitution of methionine with leucine (M918L), which is well known to be responsible for super knockdown resistance in some pest species. Another non-synonymous substitution, a valine (GTT) to alanine (GCT) replacement at amino acid 1010 (V1010A) was identified in our study and was associated with lambda-cyhalothrin resistance., Conclusion: We have characterized a known kdr mutation and identified a novel mutation in the voltage-gated sodium channel gene of Thrips tabaci associated with resistance to lambda-cyhalothrin. This gene region and these mutations are expected to be useful in the development of a diagnostic test to detect kdr resistance in many onion thrips populations., (© 2013 Society of Chemical Industry.)

Thalamocortical axons (TCAs) pass through the prethalamus in the first step of their neural circuit formation. Although it has been supposed that the prethalamus is an intermediate target for thalamocortical projection formation, much less is known about the molecular mechanisms of this targeting. Here, we demonstrated the functional implications of the prethalamus in the formation of this neural circuit. We show that Olig2 transcription factor, which is expressed in the ventricular zone (VZ) of prosomere 3, regulates prethalamus formation, and loss of Olig2 results in reduced prethalamus size in early development, which is accompanied by expansion of the thalamic eminence (TE). Extension of TCAs is disorganized in the Olig2-KO dorsal thalamus, and initial elongation of TCAs is retarded in the Olig2-KO forebrain. Microarray analysis demonstrated upregulation of several axon guidance molecules, including Epha3 and Epha5, in the Olig2-KO basal forebrain. In situ hybridization showed that the prethalamus in the wild type excluded the expression of Epha3 and Epha5, whereas loss of Olig2 resulted in reduction of this Ephas-negative area and the corresponding expansion of the Ephas-positive TE. Dissociated cultures of thalamic progenitor cells demonstrated that substrate-bound EphA3 suppresses neurite extension from dorsal thalamic neurons. These results indicate that Olig2 is involved in correct formation of the prethalamus, which leads to exclusion of the EphA3-expressing region and is crucial for proper TCA formation. Our observation is the first report showing the molecular mechanisms underlying how the prethalamus acts on initial thalamocortical projection formation.

A colony of social insects is not only an aggregation of individuals but also a functional unit. To achieve adaptive social behavior in fluctuating environmental conditions, in addition to coordination of physiological status in each individual, the whole colony is coordinated by interactions among colony members. The study on the regulation of social-insect colonies is termed "social physiology." Termites, a major group of social insects, exhibit many interesting phenomena related to social physiology, such as mechanisms of caste regulation in a colony. In their colonies, there are different types of individuals, i.e., castes, which show distinctive phenotypes specialized in specific colony tasks. Termite castes comprise reproductives, soldiers and workers, and the caste composition can be altered depending on circumstances. For the regulation of caste compositions, interactions among individuals, i.e., social interactions, are thought to be important. In this article, we review previous studies on the adaptive meanings and those on the proximate mechanisms of the caste regulation in termites, and try to understand those comprehensively in terms of social physiology. Firstly, we summarize classical studies on the social interactions. Secondly, previous studies on the pheromone substances that mediate the caste regulatory mechanisms are overviewed. Then, we discuss the roles of a physiological factor, juvenile hormone (JH) in the regulation of caste differentiation. Finally, we introduce the achievements of molecular studies on the animal sociality (i.e., sociogenomics) in terms of social physiology. By comparing the proximate mechanisms of social physiology in termites with those in hymenopterans, we try to get insights into the general principles of social physiology in social animals.

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

Inflammation and glycemic control are important prognosis-related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti-inflammatory effects of monotherapy with linagliptin-a dipeptidase-4 inhibitor-in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin-6 (IL-6), high-sensitivity C-reactive protein, GA, blood glucose, and active glucagon-like peptide-1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low-density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL-6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL-6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon-like peptide-1 levels increased 2.5-fold during the treatment. Over the 6-month treatment period, body weight and levels of high-sensitivity C-reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti-inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes., (© 2014 International Society for Hemodialysis.)

Opn5 is one of the recently identified opsin groups that is responsible for nonvisual photoreception in animals. We previously showed that a chicken homolog of mammalian Opn5 (Opn5m) is a Gi-coupled UV sensor having molecular properties typical of bistable pigments. Here we demonstrated that mammalian Opn5m evolved to be a more specialized photosensor by losing one of the characteristics of bistable pigments, direct binding of all-trans-retinal. We first confirmed that Opn5m proteins in zebrafish, Xenopus tropicalis, mouse, and human are also UV-sensitive pigments. Then we found that only mammalian Opn5m proteins lack the ability to directly bind all-trans-retinal. Mutational analysis showed that these characteristics were acquired by a single amino acid replacement at position 168. By comparing the expression patterns of Opn5m between mammals and chicken, we found that, like chicken Opn5m, mammalian Opn5m was localized in the ganglion cell layer and inner nuclear layer of the retina. However, the mouse and primate (common marmoset) opsins were distributed not in the posterior hypothalamus (including the region along the third ventricle) where chicken Opn5m is localized, but in the preoptic hypothalamus. Interestingly, RPE65, an essential enzyme for forming 11-cis-retinal in the visual cycle is expressed near the preoptic hypothalamus of the mouse and common marmoset brain but not near the region of the chicken brain where chicken Opn5m is expressed. Therefore, mammalian Opn5m may work exclusively as a short wavelength sensor in the brain as well as in the retina with the assistance of an 11-cis-retinal-supplying system.

Sexual dimorphisms in trait expression are widespread among animals and are especially pronounced in ornaments and weapons of sexual selection, which can attain exaggerated sizes. Expression of exaggerated traits is usually male-specific and nutrition sensitive. Consequently, the developmental mechanisms generating sexually dimorphic growth and nutrition-dependent phenotypic plasticity are each likely to regulate the expression of extreme structures. Yet we know little about how either of these mechanisms work, much less how they might interact with each other. We investigated the developmental mechanisms of sex-specific mandible growth in the stag beetle Cyclommatus metallifer, focusing on doublesex gene function and its interaction with juvenile hormone (JH) signaling. doublesex genes encode transcription factors that orchestrate male and female specific trait development, and JH acts as a mediator between nutrition and mandible growth. We found that the Cmdsx gene regulates sex differentiation in the stag beetle. Knockdown of Cmdsx by RNA-interference in both males and females produced intersex phenotypes, indicating a role for Cmdsx in sex-specific trait growth. By combining knockdown of Cmdsx with JH treatment, we showed that female-specific splice variants of Cmdsx contribute to the insensitivity of female mandibles to JH: knockdown of Cmdsx reversed this pattern, so that mandibles in knockdown females were stimulated to grow by JH treatment. In contrast, mandibles in knockdown males retained some sensitivity to JH, though mandibles in these individuals did not attain the full sizes of wild type males. We suggest that moderate JH sensitivity of mandibular cells may be the default developmental state for both sexes, with sex-specific Dsx protein decreasing sensitivity in females, and increasing it in males. This study is the first to demonstrate a causal link between the sex determination and JH signaling pathways, which clearly interact to determine the developmental fates and final sizes of nutrition-dependent secondary-sexual characters.

Aim: Although perihepatic lymph node enlargement (PLNE) is reportedly associated with the negative outcome of interferon therapy for chronic hepatitis C, there were limitations in that the results were obtained in patients with various genotypes, viral loads and treatment regimens. We aimed to precisely clarify the significance of PLNE in interferon therapy for chronic hepatitis C., Methods: Between December 2004 and June 2005, 112 patients with hepatitis C virus (HCV) genotype 1 and HCV RNA of more than 100 KIU/mL were enrolled, who underwent pegylated interferon-α plus ribavirin therapy thereafter. PLNE was defined as a perihepatic lymph node of more than 1 cm in the longest axis by ultrasonography., Results: The sustained virological response (SVR) rate was lower in patients with PLNE (4/22, 18.2%) than in those without (37/90, 41.1%; P = 0.045) and viral load decline was smaller in patients with PLNE than in those without (P = 0.028). The proportion of PLNE positive patients was the smallest in the SVR group (P = 0.033) among the patient groups divided by the treatment outcome. PLNE was retained as a negative predictor for SVR by multivariate logistic regression analysis (P = 0.012). Furthermore, PLNE was not significantly associated with the mutations at HCV core protein and at interferon sensitivity-determining region, or interleukin-28B polymorphism in 45 patients with HCV genotype 1, enrolled between December 2011 and March 2012., Conclusion: PLNE is a negative predictor for SVR in patients with HCV genotype 1 and HCV RNA of more than 100 KIU/mL treated with pegylated interferon-α plus ribavirin, independent of other known predictors for SVR., (© 2013 The Japan Society of Hepatology.)

Sexually-selected exaggerated traits tend to be unusually reliable signals of individual condition, as their expression tends to be more sensitive to nutritional history and physiological circumstance than that of other phenotypes. As such, these traits are the foundation for many models of sexual selection and animal communication, such as "handicap" and "good genes" models. Exactly how expression of these traits is linked to the bearer's condition has been a central yet unresolved question, in part because the underlying physiological mechanisms regulating their development have remained largely unknown. Recent discoveries across animals as diverse as deer, beetles, and flies now implicate the widely conserved insulin-like signaling pathway, as a common physiological mechanism regulating condition-sensitive structures with extreme growth. This raises the exciting possibility that one highly conserved pathway may underlie the evolution of trait exaggeration in a multitude of sexually-selected signal traits across the animal kingdom., (© 2013 WILEY Periodicals, Inc.)

In Daphnia pulex, juveniles form "neckteeth" a defensive structure on their heads, in response to predatory kairomones released by Chaoborus larvae. This phenomenon provides a model experimental system for the study of developmental mechanisms and evolutionary processes in predator-induced polyphenisms. Although it is thought that kairomone signals are sensed and converted into physiological signals resulting in morphological changes, little is known about the endocrine and physiological mechanisms of this process. Juvenile hormones and related chemicals, that is, juvenoids, are key hormones responsible for various physiological events in insects, including polyphenisms. In some crustaceans, methyl farnesoate (MF) is known to act as a juvenoid. In order to investigate the functions of juvenoids in defense morph formation, we treated daphnids with MF as well as JHIII (Juvenile Hormone III, an insect juvenoid) and fenoxycarb (a synthetic juvenile hormone analog) during their developmental stages. Strikingly, in the first-instar juveniles, all examined juvenoids stimulated the formation of neckteeth only in the presence of kairomones, not by themselves. This juvenoid effect on the neckteeth formation might be due to disturbance of the JH pathway. Juvenoid treatments reduced tail-spine length, whereas predatory kairomones are known to elongate tail spine. These results suggest that other physiological factors are responsible for the tail-spine elongation., (© 2013 Wiley Periodicals, Inc.)

Raman spectroscopy has been used in chemistry and physics to investigate the fundamental process involving light and phonons. The carbon nanohorn introduces a new subject to Raman spectroscopy, namely topology. We show theoretically that a photoexcited carrier with a nonzero winding number activates a topological D Raman band through the Aharonov-Bohm effect. The topology-induced D Raman band can be distinguished from the ordinary D Raman band for a graphene edge by its peak position.

Aim: Although perihepatic lymph node enlargement (PLNE) is known as a common finding in chronic liver disease, it can be found occasionally at a general health examination. We aimed to clarify the clinical significance of PLNE in general., Methods: Between January 2008 and December 2011, 4234 subjects were enrolled, who underwent a general health examination at the University of Tokyo Hospital., Results: PLNE was observed in 69 (1.6%) subjects, among whom 17 (0.4%) had liver disorders and 13 (0.3%) had malignancy, one of whom had both. No disorders were determined in the remaining 40 subjects (0.9%). Among 17 subjects with liver disorder-associated PLNE, anti-hepatitis C virus (HCV) antibody was determined in 11 and serum alanine aminotransferase levels were less than 40 U/L in eight. Among 13 subjects with malignancy-associated PLNE, para-aortic lymph nodes were also enlarged in eight. Among 40 subjects with PLNE of unknown etiology, 27 could be followed up for the mean period of 2.08 years, where no underlying disorders were newly determined with largely unaltered size of PLNE., Conclusion: The incidence of PLNE in the general population may vary with the prevalence of chronic liver disease, especially HCV infection. When PLNE is observed, liver disorders should be first surveyed including HCV infection even with normal serum alanine aminotransferase levels. PLNE with para-aortic lymph node enlargement may be suggestive of a malignant lesion. The incidence of PLNE of unknown etiology may be approximately 1% in the general population, which may be just followed up without further change., (© 2012 The Japan Society of Hepatology.)

Most aphids exhibit wing polyphenism, in which winged and wingless females are produced depending on aphid densities. Although juvenile hormone (JH) has been implicated in the regulation of aphid wing polyphenism, relatively few studies examining the direct relationship between JH titer and resultant wing morphs have been undertaken. We therefore investigated the relationship between JH III titer and the development of wing morphs in the vetch aphid Megoura crassicauda during postembryonic development. JH III measurements by liquid chromatography-mass spectrometry (LC-MS) revealed that, at the third instar, presumptive wingless nymphs had significantly higher JH III titers than winged nymphs. In winged nymphs at the third instar, JH III application inhibited wing development resulting in the appearance of winged/wingless intermediates as well as juvenilized individuals with supernumerary molting. These results suggest that JH III plays an important role in wing-morph differentiation during postembryonic development., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Perihepatic lymph node enlargement (PLNE) is a common ultrasound finding in chronic hepatitis C patients. Although PLNE is considered to reflect the inflammatory response to hepatitis C virus (HCV), its clinical significance remains unclear., Methods: Between December 2004 and June 2005, we enrolled 846 chronic hepatitis C patients in whom adequate ultrasound examinations had been performed. PLNE was defined as a perihepatic lymph node that was at least 1 cm in the longest axis by ultrasonography. We analyzed the clinical features of patients with PLNE and prospectively investigated the association between PLNE and hepatocellular carcinoma (HCC) development., Results: We detected PLNE in 169 (20.0%) patients. Female sex, lower body mass index (BMI), and HCV serotype 1 were independently associated with the presence of PLNE. However, there were no significant differences in liver function tests, liver stiffness, and hepatitis C viral loads between patients with and without PLNE. During the follow-up period (mean 4.8 years), HCC developed in 121 patients. Unexpectedly, patients with PLNE revealed a significantly lower risk of HCC development than those without PLNE (p = 0.019, log rank test). Multivariate analysis revealed that the presence of PLNE was an independent negative predictor of HCC development (hazard ratio 0.551, p = 0.042). In addition, the sustained viral response rate in patients who received interferon (IFN) therapy was significantly lower in patients with PLNE than in patients without PLNE., Conclusions: Patients with PLNE had a lower risk of HCC development than those without PLNE. This study may provide new insights into daily clinical practice and the pathophysiology of HCV-induced hepatitis and hepatocarcinogenesis.

Aim: To evaluate the long-term efficacy of monotherapy with the dipeptidase-4 inhibitor alogliptin benzoate in hemodialysis (HD) patients with type 2 diabetes., Methods: Sixteen diabetic HD patients with inadequate glycemic control (hemoglobin A1c (HbA1c) level >6.5% and glycated albumin (GA) level >20%) on diet and exercise participated in the study. No patients were taking other oral antidiabetic drugs or receiving insulin therapy. Alogliptin 6.25 mg was administered to patients once daily. HbA1c, GA levels were obtained before and after 2 years of treatment. Body weight and active glucagon-like peptide-1, blood glucose, insulin, C-peptide immunoreactivity, glucagon, albumin, hemoglobin, and total cholesterol levels were also examined before and after treatment., Results: Both HbA1c and GA levels decreased after starting alogliptin administration. As compared to the pretreatment levels, HbA1c and GA levels significantly decreased at 3 and 18 months, respectively, after starting alogliptin administration. HbA1c and GA levels decreased from 7.1 ± 0.2 to 5.8 ± 1.6% and from 22.5 ± 0.7 to 19.6 ± 0.6%, respectively, 24 months after beginning treatment. Glucagon-like peptide-1 levels (8.9 ± 5.7 pmol/l before treatment) doubled after treatment. Body weight and blood glucose, insulin, C-peptide immunoreactivity, glucagon, albumin, hemoglobin, and total cholesterol levels did not change with treatment. Only one significant adverse effect, a drug-related rash, was seen in 1 patient., Conclusion: Long-term (2-year) effects of alogliptin benzoate monotherapy suggest its efficacy as a new treatment strategy in diabetic HD patients., (Copyright © 2013 S. Karger AG, Basel.)

The objectives of the present study are (1) to compare the cardioankle vascular index (CAVI), ankle-brachial index (ABI), and carotid artery intima-media thickness (CA-IMT) between HD patients with and without type 2 diabetes (T2D) or prevalence of cardiovascular (CV) disease and (2) also to evaluate the relationship of these indices with CA-IMT in these patients according to ABI levels. This study consisted of 132 HD patients with T2D and the same number of patients without T2D. The patients with diabetes or prevalence of CV disease had significantly higher CA-IMT and lower ABI values than those without diabetes or prevalence of CV disease, respectively. Although diabetic patients had higher CAVI than those without diabetes, CAVI did not differ between patients with or without prevalence of CV disease. In univariate analysis, CA-IMT was more strongly correlated with ABI than CAVI. However, the opposite was true in patients with an ABI value of more than 0.95. Both indices were significantly correlated with CA-IMT although ABI was a powerful determinant than CAVI. It appears that both indices are associated with CA-IMT in HD patients, especially with an ABI value of more than 0.95.

Background: It is very important to evaluate atherosclerosis at an early stage since cardiovascular disease is the main cause of death in patients with end stage renal disease. The purpose of our study was to examine which of the following parameters of atherosclerosis is the best index for the prediction of cardiovascular death or events in hemodialysis patients: intima media thickness (IMT), ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI), and whether visceral fat area (VFA) and subcutaneous fat area (SFA), also predict those events., Methods: VFA, SFA, IMT, ABI and CAVI were measured using CT or a dedicated device in 270 hemodialysis patients(age: 63.3 +/- 12.3 years, male 56.3%)., Results: During a median follow-up period of 54 months, cardiovascular deaths or events occurred in 92 (34.1%) patients. Seventy (25.9%) patients died, 27 (38.6%) of them due to cardiovascular events. Whereas several baseline clinical covariates showed an associated risk for composite cardiovascular events in a univariate Cox proportional hazards analysis, almost all of them became insignificant when analyzed together. Only age, SFA, and a prevalence of diabetes remained significant in multivariate analysis. When both IMT and ABI were included in this model, all other covariates became insignificant, while ABI, but not IMT, was also related to the prediction of cardiovascular death on top of age and SFA., Conclusions: Both ABI and IMT were useful predictors for composite cardiovascular events, with ABI being also associated with a risk for cardiovascular deaths. In addition, SFA was a useful predictor for both cardiovascular events and cardiovascular deaths.

The emergence of larger brains with large numbers of neurons is an evolutionary innovation in mammals and birds. However, the corresponding changes in cortical developmental programmes during amniote evolution are poorly understood. Here we examine the cortical development of Madagascar ground geckos, and report unique characteristics of their reptilian cortical progenitors. The rates of proliferation and neuronal differentiation in the gecko cortex are much lower than those in other amniotes. Notch signalling is highly activated in the gecko cortical progenitors, which provides a molecular basis for the low rate of cortical neurogenesis. Interestingly, multiple neuron subtypes are sequentially generated in the gecko cortex, similar to other amniotes. These results suggest that changes in the regulation of cortical neural progenitors have accelerated neurogenesis and provided encephalization in mammalian and archosaurian lineages. In addition, the temporal regulation for making cortical neuronal subtypes has evolved in a common ancestor(s) of amniotes.

Genetic disorders are usually considered to be caused by harmful gene mutations, as well as by chromosomal aberrations, including small insertions, duplications and/or deletions. However, as infertile individuals often arise among the offspring of crosses between two fertile mouse strains, we postulate that a certain combination of 'normal' genes with neither gene mutations nor chromosomal aberrations can cause such serious phenotypic alterations as reproductive dysfunction. In this study, we show evidence that a combination of multiple normal genes from two different normal mouse strains manifests a wide range of male reproductive dysfunctions, from benign changes to complete infertility. These abnormal phenotypes are thought to have occurred by epistatic interactions of alleles., (© 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.)

An ultrathin (one monolayer thick) InN single quantum well (SQW) formed on a step-free GaN surface shows very sharp violet PL emission. The size (16 μm in diameter) is large enough for state-of-the-art nanotechnology to handle. Longer wavelength emissions, such as green and red, are expected by increasing the thickness of the SQW through the utilization of the quantum size effect., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A definition of the scope of aromatic substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examination of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addition to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aqueous buffer may be radical mediated, the studies provide new opportunities for the preparation of previously inaccessible vinblastine analogs and define powerful new methodology for the synthesis of indole-containing natural and unnatural products.

The B10.M mouse strain represents a model for male subfertility as it produces a significantly low number of offspring. The only known male reproductive phenotype of this strain is its high frequency of sperm-head morphological abnormalities (44.7 ± 2.4 %). We previously reported that this phenotype was the product of two recessive loci. In this study we mapped the loci causing the high frequency of sperm-head morphological abnormalities in this strain using F2 animals produced by crossing B10.M and C3H mice. Quantitative trait loci (QTL) analysis (n = 178) identified two recessive genes, one on Chromosome (Chr) 1 (LOD score = 30.585) and one on Chr 4 (LOD score = 4.532). Further analysis (n = 854) mapped the locus on Chr 1 between Ercc5 (23.55 cM) and D1Mit528 (25.95 cM) and the locus on Chr 4 between D4Mit148 (69.48 cM) and D4Mit170 (70.47 cM). It was also found that the effects of these two loci were not independent. The major locus on Chr 1 determines the expression of sperm-head abnormalities, while the locus on Chr 4 enhances the frequency of abnormalities only when the genotype of the Chr 1 locus is homozygous for the B10.M allele. The major locus on Chr 1 was named sperm-head morphology 1 (Shm1), while the modifier locus on Chr 4 was named sperm-head morphology 2 (Shm2).

Sexually selected exaggerated traits are often coupled with modifications in other nontarget traits. In insects with weapons, enlargements of nontarget characters that functionally support the weapon often occur (i.e. supportive traits). The support of sexual traits requires developmental coordination among functionally related multiple traits-an explicit example of morphological integration. The genetic theory predicts that developmental integration among different body modules, for which development is regulated via different sets of genes, is likely to be coordinated by pleiotropic factors. However, the developmental backgrounds of morphological integrations are largely unknown. We tested the hypothesis that the juvenile hormone (JH), as a pleiotropic factor, mediates the integration between exaggerated and supportive traits in an armed beetle Gnatocerus cornutus. During combat, males of this beetle use exaggerated mandibles to lift up their opponents with the supportive traits, that is, the head and prothoracic body parts. Application of methoprene, a JH analog (JHA), during the larval to prepupal period, induced the formation of large mandibles relative to the body sizes in males. Morphometric examination of nontarget traits elucidated an increase in the relative sizes of supportive traits, including the head and prothoracic body parts. In addition, reductions in the hind wing area and elytra length, which correspond to flight and reproductive abilities, were detected. Our findings are consistent with the genetic theory and support the idea that JH is a key pleiotropic factor that coordinates the developmental integration of exaggerated traits and supportive characters, as well as resource allocation trade-offs., (© 2012 Wiley Periodicals, Inc.)

The mammalian cerebral cortex, which is stratified into six layers, has functional domains that vertically span the six layers, thereby requiring tight interlaminar connectivity within a domain. The synaptic connections in individual layers are first broadly formed under predetermined programs and later reinforced between neurons which reside in the same functional domain via experience-dependent reorganization during the critical period. However, the molecular mechanisms that control these two processes within each layer are still unclear. Therefore, we performed a differential screen for candidates and found seven genes with layer-specific expression during postnatal development of cat visual cortex. APLP1, a transmembrane protein mediating synaptogenesis, started dual-layer expression in layers 2/3 and 5 before the critical period, suggesting that it might execute coarse synapse formation of these layers. STMN2 (SCG10), which promotes microtubule turnover, was unique, as it dramatically shifted its dual-layer distribution from layers 2/3 and 5 to the deeper layers 4 and 6 at the onset of the critical period; it lost this new expression pattern in the adult. Surprisingly, brief dark rearing disturbed the shift in its dual-layer distribution around the onset of the critical period. Thus, by accelerating structural remodeling, STMN2 (SCG10) might launch experience-dependent reorganization of particular layers., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

We investigated the Au-assisted growth of alternating InAsP/InP heterostructures in wurtzite InP nanowires on InP(111)B substrates for constructing multiple-quantum-dot structures. Vertical InP nanowires without stacking faults were obtained at a high PH(3)/TMIn mole flow ratio of 300-1000. We found that the growth rate changed largely when approximately 40 min passed. Ten InAsP layers were inserted in the InP nanowire, and it was found that both the InP growth rate and the background As level increased after the As supply. We also grew the same structure using TBAs/TBP and could reduce the As level in the InP segments. A simulation using a finite-difference time-domain method suggests that the nanowire growth was dominated by the diffusion of the reaction species with long residence time on the surface. For TBAs/TBP, when the source gases were changed, the formed surface species showed a short diffusion length so as to reduce the As background after the InAsP growth.

Craniopharyngiomas are difficult to treat. The extended transsphenoidal approach has recently been described in several small series. We describe the usefulness of microscopy-assisted angled endoscopy for visualizing vital structures such as tumor attachment or tumor invasion to the pituitary stalk to achieve confident radical tumor removal. Between 2006 and 2010, 15 patients underwent the microscopy-assisted extended transsphenoidal approach for resection of entirely suprasellar craniopharyngiomas. Fourteen patients had the transinfundibular type, and one had the transinfundibular type with extension to the third ventricle. We observed color change within the pituitary stalk by endoscopy. The pituitary stalk was cut intentionally in 10 patients because of suspected tumor invasion surrounding the stalk. Total removal was accomplished in nine patients. Pathological specimens from the pituitary stalk showed tumor invasion spreading over the surface of the pituitary stalk, shown by a discolored pituitary stalk, and this was essential for confident radical tumor removal. Even after stalk resection, postoperative diabetes insipidus was minimal when a bright signal on T1 in the posterior lobe was not observed with preoperative magnetic resonance imaging. Confident radical tumor removal is possible with the introduction of the endoscopy-assisted microscopic extended transsphenoidal approach.

Most aphids show reproductive polyphenism, i.e. they alternate their reproductive modes from parthenogenesis to sexual reproduction in response to short photoperiods. Although juvenile hormone (JH) has been considered a likely candidate for regulating the transition from asexual to sexual reproduction after photoperiod sensing, there are few studies investigating the direct relationship between JH titres and the reproductive-mode change. In addition, the sequencing of the pea aphid genome has allowed identification of the genes involved in the JH pathway, which in turn allows us to examine their expression levels in relation to the reproductive-mode change. Using liquid chromatography-mass spectrometry in the pea aphid, JHIII titre was shown to be lower in aphids producing sexual morphs under short-day conditions than in aphids producing parthenogenetic morphs under long-day conditions. The expression levels of genes upstream and downstream of JH action were quantified by real-time quantitative reverse-transcription-PCR across the reproductive-mode change. The expression level of JH esterase, which is responsible for JH degradation, was significantly higher in aphids reared under short-day conditions. This suggests that the upregulation of the JH degradation pathway may be responsible for the lower JHIII titre in aphids exposed to short-days, leading to the production of sexual morphs., (© 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.)

Background: Previously, we reported an increase in expressions of mRNA of Cu/Zn-superoxide dismutase (SOD) in leukocytes of hemodialysis (HD) patients, and speculated that the increase is associated with oxidative stress on the leukocyte membrane due to the HD process., Methods: Expressions of Cu/Zn-SOD mRNA in leukocytes, contents of plasma SOD, and malondialdehyde (MDA) in leukocyte and erythrocyte membranes, respectively, were examined in 25 HD patients and 14 healthy volunteers. These were also determined after using a vitamin E-coated dialyzer (VE dialyzer) for 4 weeks., Results: All values were significantly higher in HD patients. A significant correlation was found between leukocyte Cu/Zn-SOD mRNA expression and membrane MDA. After using the VE dialyzer, all values were significantly lowered, showing a significant correlation between changing rate of leukocyte Cu/Zn-SOD mRNA expression and membrane MDA., Conclusion: In HD patients, oxidative stress is generated on the leukocyte membrane, and the level of Cu/Zn-SOD mRNA in leukocytes can be a useful oxidative stress marker., (Copyright © 2011 S. Karger AG, Basel.)

Heterogeneous classes of neurons are present in the spinal cord and are essential for its function. Expression patterns of transcription factors in neural progenitor cells determine neuron subtypes during development. Nkx2.2 is expressed in the progenitor cell pool located just ventrally to the Olig2-positive pool and is indispensable for V3 interneuron generation in the spinal cord and also for visceral motoneuron generation in the hindbrain. However, whether Nkx2.2-positive progenitor cells generate diverse classes of neuron is not fully understood. Using a chick lineage tracing method in a genetically-defined manner, we found that Nkx2.2-expressing progenitor cells differentiate into general visceral motoneurons as well as sim1-positive V3 interneurons. Surprisingly, we further observed that Nkx2.2-expressing progenitors differentiate into somatic motoneuron. Our findings suggest that the different classes of motoneurons are derived from more complex sources than were previously expected in the chick spinal cord.

Diphenylprolinol silyl ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a δ-formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6π) and the enamine double bond (2π) generated from the formyl group in the substrates and the diphenylprolinol silyl ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the following: (i) The intermolecular [6 + 2] cycloaddition of a fulvene and an enamine double bond proceeds in a stepwise mechanism via a zwitterionic intermediate. (ii) On the other hand, the intramolecular [6 + 2] cycloaddition leading to the cis-fused triquinane skeleton proceeds in a concerted mechanism via a highly asynchronous transition state. (iii) The fulvene functionality and the enamine double bond adopt the gauche-syn conformation during the C-C bond formation processes in the [6 + 2] cycloaddition. (iv) The energy profiles calculated for the intramolecular reaction explain the observed exclusive formation of the cis-fused triquinane derivatives in the [6 + 2] cycloaddition reactions. The reasons for the enantioselectivity seen in these [6 + 2] cycloaddition reactions are also discussed., (© 2011 American Chemical Society)

A study on the impact of catharanthine C10 and C12 indole substituents on the biomimetic Fe(III)-mediated coupling with vindoline led to the discovery and characterization of two new and substantially more potent derivatives, 10'-fluorovinblastine and 10'-fluorovincristine. In addition to defining a pronounced and unanticipated substituent effect on the biomimetic coupling, fluorine substitution at C10', which minimally alters the natural products, was found to uniquely enhance the activity 8-fold against both sensitive (IC(50) = 800 pM, HCT116) and vinblastine-resistant tumor cell lines (IC(50) = 80 nM, HCT166/VM46). As depicted in the X-ray structure of vinblastine bound to tubulin, this site resides at one end of the upper portion of the T-shaped conformation of the tubulin-bound molecule, suggesting the 10'-fluorine substituent makes critical contacts with the protein at a hydrophobic site uniquely sensitive to steric interactions.

In submammalian animals including chicks, the retina contains oligodendrocytes (OLs), and axons in the optic fiber layer are wrapped with compact myelin within the retina; however, the expression of myelin genes in the chick retina has not been demonstrated yet. In the present study, we examined the expression of three myelin genes (proteolipid protein, PLP; myelin basic protein, MBP; cyclic nucleotide phosphodiesterase, CNP) and PLP in the developing chick retina, in comparison to the localization of Mueller cells. In situ hybridization demonstrated that all three myelin genes began to be expressed at E14 in the chick embryo retina. They are mostly restricted to the ganglion cell layer and the optic fiber layer, with a few exceptions in the inner nuclear layer where Mueller cells reside; however, PLP mRNA+ cells do not express glutamine synthetase, or vice versa. The present results elucidate that myelin genes are expressed only by OLs that are mostly localized in the innermost layer of the developing chick retina., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The regulation of caste differentiation is essential to insect eusociality. Termite soldiers are sterile and cannot eat by themselves because they have specialized mouth morphology. Almost all termite species have a soldier caste, and the soldier ratio per colony is maintained at a low level, probably by elaborate regulatory mechanisms. Although the soldier presence is considered to negatively affect soldier differentiation in all examined species, the detailed mechanism remains unclear. Presoldier differentiation can be induced artificially by juvenile hormone (JH) application to workers, showing that JH is a key factor underlying the regulation of soldier differentiation. In this study, to elucidate physiological changes in workers because of the soldier presence during the molt into presoldiers, JH III applications and JH titer quantifications were carried out in the rhinotermitid termite Reticulitermes speratus. Firstly, the effects of soldier presence before the molt into presoldiers induced by JH III application to workers were investigated. The rates of presoldier molt induced by the treatments with soldiers were significantly lower than those without soldiers. Secondly, worker JH titers in the presence or absence of soldiers were quantified by LC-MS on day 0, 5, 10, and 15 after JH application. Results indicated that the worker JH titers (endogenous+applied JH III) in the presence of soldiers were significantly lower than those without soldiers on day 5 after the JH treatment. On days 10 and 15, such soldier effects were not observed. Finally, the effective duration of soldier presence after the JH application was elucidated. A 4 day period of co-existence with soldiers suppressed presoldier differentiation, suggesting that the soldier presence rapidly decreased the JH titer in other colony members (i.e., workers), resulting in the inhibition of presoldier production., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Magneto-optic Kerr microscopy was employed to investigate the spin-orbit interactions of electrons traveling in semiconductor quantum wells using surface acoustic waves (SAWs). Two-dimensional images of the spin flow induced by SAWs exhibit anisotropic spin precession behaviors caused by the coexistence of different types of spin-orbit interactions. The dependence of spin-orbit effective magnetic fields on SAW intensity indicates the existence of acoustically controllable spin-orbit interactions resulting from the strain and Rashba contributions induced by the SAWs., (© 2011 American Physical Society)

Carrier-induced dynamic backaction in micromechanical resonators is demonstrated. Thermal vibration of an n-GaAs/i-GaAs bilayer cantilever is amplified by optical band-gap excitation, and for the excitation power above a critical value, self-oscillations are induced. These phenomena are found in the [1[over ¯]10]-oriented cantilever, whereas the damping (deamplification) is observed in the [1[over ¯]10] orientation. This optomechanical coupling does not require any optical cavities but is instead based on the piezoelectric effect that is generated by photoinduced carriers.

In the spinal cord, generation of oligodendrocytes (OLs) is totally dependent on the presence of Olig2, a basic helix-loop-helix transcription factor. However, it also requires Nkx2.2 for its generation, whose expression follows the expression of Olig2. Although it is believed that oligodendrocytes originate from the pMN domain, Nkx2.2 is present in the p3 domain located ventral to the pMN domain. According to recent reports, it is possible that oligodendrocytes are directly derived from the p3 domain in addition to the pMN domain in the chick spinal cord. We examined this hypothesis in this paper. To analyze OL development in the spinal cord, chick embryos are widely used for genetic modification by electroporation or for transplantation experiments, because it is relatively easy to manipulate them compared with mouse embryos. However, genetic modification by electroporation is not appropriate for glial development analyses because glia proliferate vigorously before maturation. In order to overcome these problems, we established a novel method to permanently introduce exogenous gene into a specific cell type. We introduced the CAT1 gene, a murine retroviral receptor, by electroporation followed by injection of murine retrovirus. By using this method, we successfully transduced murine retrovirus into the chick neural tube. We analyzed cell lineage from the p3 domain by restricting CAT1 expression by Nkx2.2-enhancer and found that most of the labeled cells became OLs when the cells were labeled at cE4. Moreover, the labeled OLs were found throughout the white matter in the spinal cord including the most dorsal spinal cord. Thus p3 domain directly generates spinal cord OLs in the chick spinal cord., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The morphological diversity of insects is one of the most striking phenomena in biology. Evolutionary modifications to the relative sizes of body parts, including the evolution of traits with exaggerated proportions, are responsible for a vast range of body forms. Remarkable examples of an insect trait with exaggerated proportions are the mandibular weapons of stag beetles. Male stag beetles possess extremely enlarged mandibles which they use in combat with rival males over females. As with other sexually selected traits, stag beetle mandibles vary widely in size among males, and this variable growth results from differential larval nutrition. However, the mechanisms responsible for coupling nutrition with growth of stag beetle mandibles (or indeed any insect structure) remain largely unknown. Here, we demonstrate that during the development of male stag beetles (Cyclommatus metallifer), juvenile hormone (JH) titers are correlated with the extreme growth of an exaggerated weapon of sexual selection. We then investigate the putative role of JH in the development of the nutritionally-dependent, phenotypically plastic mandibles, by increasing hemolymph titers of JH with application of the JH analog fenoxycarb during larval and prepupal developmental periods. Increased JH signaling during the early prepupal period increased the proportional size of body parts, and this was especially pronounced in male mandibles, enhancing the exaggerated size of this trait. The direction of this response is consistent with the measured JH titers during this same period. Combined, our results support a role for JH in the nutrition-dependent regulation of extreme mandible growth in this species. In addition, they illuminate mechanisms underlying the evolution of trait proportion, the most salient feature of the evolutionary diversification of the insects.

The examination of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 methyl ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16' methyl ester with an ethyl ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold) or a primary carboxamide (>1000-fold) led to surprisingly large reductions in cytotoxic activity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background and Aim: The mechanism responsible for thrombocytopenia in chronic liver diseases (CLD) is not yet fully understood. The prevalence of thrombocytopenia has been reported to be higher in patients with hepatitis C virus-related hepatocellular carcinoma (CLD-C) than in those with hepatitis B virus-related hepatocellular carcinoma (CDC-B). We have examined the potential difference in thrombocytopenia between patients with CLD-B and those with CLD-C in terms of liver fibrosis adjustment and splenomegaly., Methods: The study cohort consisted of 102 patients with CLD-B and 143 patients with CLD-C were enrolled. Liver stiffness, which is reported to be well correlated with the degree of liver fibrosis, was measured by transient elastography., Results: The analysis of covariance with liver stiffness as a covariate revealed that the platelet count was lower in CLD-C patients than in CLD-B patients. Following stratification for liver stiffness, thrombocytopenia was found to be more severe in CLD-C patients than CLD-B patients with advanced liver stiffness, whereas the degree of splenomegaly was not significantly different. The plasma thrombopoietin level was not different between CLD-B and CLD-C patients with advanced liver stiffness, and the immature platelet number was lower in CLD-C patients despite thrombocytopenia being more severe in these patients., Conclusions: CLD-C patients with advanced liver stiffness presented with more severe levels of thrombocytopenia than CLD-B patients even with the same grade of splenomegaly. Impaired platelet production rather than enhanced platelet destruction may underlie the mechanism responsible for thrombocytopenia in patients with CLD.

Bacterial biofilm formation can be induced by antimicrobial and DNA damage agents. These agents trigger the SOS response, in which SOS sensor RecA stimulates auto-cleavage of repressor LexA. These observations lead to a hypothesis of a connection between stress-inducible biofilm formation and the RecA-LexA interplay. To test this hypothesis, three biofilm assays were conducted, viz. the standard 96-well assay, confocal laser scanning microscopy, and the newly developed biofilm-on-paper assay. It was found that biofilm stimulation by the DNA replication inhibitor hydroxyurea was dependent on RecA and appeared repressed by the non-cleavable LexA of Pseudomonas aeruginosa. Surprisingly, deletion of lexA led to reduction of both normal and stress-inducible biofilm formation, suggesting that the wild-type LexA contributes to biofilm formation. The decreases was not the result of poor growth of the mutants. These results suggest SOS involvement in hydroxyurea-inducible biofilm formation. In addition, with the paper biofilm assay, it was found that degradation of the biofilm matrix DNA by DNase I appeared to render the biofilms susceptible to the replication inhibitor. The puzzling questions concerning the roles of LexA in DNA release in the biofilm context are discussed.

Purpose: It is imperative for prognostic improvement of pancreatic cancer that we try to diagnose carcinoma in situ (CIS) of lesions, i.e., precursors of invasive ductal carcinomas (IDCs) at an early stage, because results of treatment of patients with IDCs themselves continue to be rather unsatisfactory., Materials and Results: We report here a case of a patient who received subtotal pancreatectomy for widespread and multifocal CISs of the pancreas after preoperative brushing cytology from the epithelium of dilated main pancreatic duct proved cancer-positive preoperatively., Conclusions: From our experience, we conclude that examination for CIS of the pancreas must be recommended whenever dilatation of relatively large pancreatic ducts is found by ultrasound or computed tomography. We should therefore advance to magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography and then cytological and/or pathological assessment of the pancreatic duct whenever non-continuous narrowing, localized dilatation, or other irregularities are encountered.

It is postulated that chickens (Gallus gallus domesticus) became domesticated from wild junglefowls in Southeast Asia nearly 10,000 years ago. Based on 19 individual samples covering various chicken breeds, red junglefowl (G. g. gallus), and green junglefowl (G. varius), we address the origin of domestic chickens, the relative roles of ancestral polymorphisms and introgression, and the effects of artificial selection on the domestic chicken genome. DNA sequences from 30 introns at 25 nuclear loci are determined for both diploid chromosomes from a majority of samples. The phylogenetic analysis shows that the DNA sequences of chickens, red and green junglefowls formed reciprocally monophyletic clusters. The Markov chain Monte Carlo simulation further reveals that domestic chickens diverged from red junglefowl 58,000+/-16,000 years ago, well before the archeological dating of domestication, and that their common ancestor in turn diverged from green junglefowl 3.6 million years ago. Several shared haplotypes nonetheless found between green junglefowl and chickens are attributed to recent unidirectional introgression of chickens into green junglefowl. Shared haplotypes are more frequently found between red junglefowl and chickens, which are attributed to both introgression and ancestral polymorphisms. Within each chicken breed, there is an excess of homozygosity, but there is no significant reduction in the nucleotide diversity. Phenotypic modifications of chicken breeds as a result of artificial selection appear to stem from ancestral polymorphisms at a limited number of genetic loci.

We report parallel aligned GaAs nanowires (NWs) with 110 orientation laterally grown on [311]B substrates via the vapor-liquid-solid mode and demonstrate their controllability and growth mechanism. We control the size, density, and site of the lateral NWs by using size- and density-selective Au colloidal particles and Au dot arrays defined by electron-beam lithography. The lateral NWs grow only along the [110] and [Formula: see text] directions and formation of the stable facets of (111)B and (001) on the sides of the lateral NWs is crucial for lateral NW growth. We clarify the growth mechanism by comparing the growth results on [311]B, (311)A, and (001) substrates and the surface energy change of lateral and freestanding NWs.

Examination of sperm head morphology is one of the requisite tests of the functional capacity of semen in reproduction. In the present study, genetic effects on morphological sperm head abnormalities in mice were investigated. The frequency of abnormal spermatozoa was determined in 17 inbred mouse strains and it was found that strain B10.M had the highest frequency of abnormal spermatozoa (44.7%). Segregation analysis was then used to show that the abnormal sperm phenotype in B10.M mice was inherited. The results indicated that this sperm abnormality was controlled by two distinct recessive alleles. It is proposed that the high frequency of the heritable abnormal sperm phenotype in the mouse B10.M strain explains the subfertility of this strain, as evidenced by its reduced litter size.

Background: Whereas visceral fat accumulation (VFA) is related to insulin resistance and atherosclerosis in both haemodialysis (HD) patients and the general population, little is known about the role of subcutaneous fat accumulation (SFA). The purpose of the present study was to examine and confirm the relationship between abdominal fat accumulation (AFA) and various clinical parameters in HD patients., Methods: Two hundred and thirty-three HD patients were recruited, including 120 with type 2 diabetes. Abdominal fat distribution was evaluated by computed tomography (CT) scans. Systemic atherosclerosis was assessed by intima-media thickness (IMT) using high-resolution B-mode ultrasonography. The insulin resistance was estimated by the homeostasis model assessment-insulin resistance (HOMA-IR)., Results: Spearman's analysis revealed that both VFA and SFA showed a significant relationship with HOMA-IR and also that SFA was correlated significantly with IMT in all HD patients. SFA was an independent risk factor associated with HOMA-IR and IMT in multiple regression analysis. Neither body mass index (BMI) nor VFA was a predominant determinant of HOMA-IR and IMT. IMT in HD patients with high SFA/low BMI groups was significantly higher than in the low SFA/high BMI groups., Conclusion: It appears that there is a close relationship between SFA and insulin resistance or atherosclerosis in HD patients. It was suggested that SFA plays important roles related to carbohydrate or lipid metabolism in HD patients.

Diphenylprolinol silyl ether was found to be an effective organocatalyst in the enantioselective and direct Michael reaction of nitroethanol and alpha,beta-unsaturated aldehydes, affording the 1-hydroxy-trans-3,4-disubstituted tetrahydropyrans after isomerization. The generated Michael addition products are useful synthetic intermediates, which can be converted into chiral tetrahydropyran with a quaternary stereocenter, 3-substituted cis- and trans-prolines, and alpha-amino acid derivatives.

Nodal staging is a crucial factor in choosing the treatment option for non-small cell lung cancer (NSCLC). However, so far as we know, a computer-based histomorphometric analysis of lymph nodes in NSCLC has never been developed. We studied 299 surgically resected lymph nodes from 108 patients with NSCLC. Microscopic digital images were analyzed with Scion Image software. Seventy lymph nodes had at least one metastatic focus. The metastasis occupancy area per node ranged from 0.01 to 209.58 mm(2) (mean, 29.58 +/- 5.87 mm(2)). The metastasis occupancy ratio ranged from 0.01% to 100% (mean, 48.70% +/- 42.10%). The short-axis diameter of malignant lymph nodes was significantly longer than that of benign lymph nodes (P = 0.0002). The average metastasis occupancy area in the regional lymph nodes of NSCLC is quite small. Various inflammatory conditions can result in a false-positive diagnosis when these techniques are used. Studies that combine analysis of primary tumor size and serum carcinoembryonic antigen (CEA) levels with imaging methods should be considered. Finally, the use of mediastinoscopy or video-assisted thoracoscopic surgery is encouraged in determining the exact nodal status in NSCLC.

Diphenylprolinol silyl ether was found to promote asymmetric, catalytic and direct alpha-benzoyloxylation of aldehydes with benzoyl peroxide to afford oxidized products in good yields with excellent enantioselectivity.

Most laboratory mice belong to a species of house mouse, Mus musculus. So far, at least three subspecies groups have been recognized; domesticus subspecies group (DOM) distributed in western Europe, musculus subspecies group (MUS) distributed in eastern Europe and northeast Asia, and castaneus subspecies group (CAS) found in southwest and southeast Asia including southern China. These subspecies are estimated to have branched off roughly one million years ago. Genetic comparison between subspecies' groups and common inbred strains (CIS) have revealed that the genetic background of CIS is derived mainly from DOM. This shows the importance of non-DOM wild mice as valuable genetic resources. We started to establish our unique strain, MSM/Ms, from MUS in Japan in 1978. In the beginning, we kept wild mice trapped in Mishima in large plastic buckets. In 1979, breeding by sister-brother mating started. The MSM/Ms inbred strain was established in 1986 and 21 years later it reached F(100). During breeding, no significant fluctuations in litter size and sex ratios have been observed. Extensive genetic analyses of chromosome C-banding pattern, biochemical markers and microsatellite DNA (MIT) markers of this strain have demonstrated the characteristics of MUS. A phylogenetic tree constructed from MIT markers has confirmed the MUS nature of MSM strain. Taken together with its genetic remoteness from CIS, MSM appears to maintain many valuable alleles for investigation of biological functions and diseases. Some of these alleles have avoided selection during breeding as either fancy mice or laboratory mice. The MSM-specific genetic traits discovered to date are discussed.