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We previously performed genetic analysis in six unrelated families with infantile limb pain episodes, characterized by cold-induced deterioration and mitigation in adolescence, and reported two new mutations p.R222H/S in SCN11A responsible for these episodes. As no term described this syndrome (familial episodic pain: FEP) in Japanese, we named it as"". In the current study, we recruited an additional 42 new unrelated Japanese FEP families, between March 2016 and March 2018, and identified a total of 11 mutations in SCN11A: p.R222H in seven families, and p.R225C, p.F814C, p.F1146S, or p.V1184A, in independent families. A founder mutation, SCN11A p.R222H was confirmed to be frequently observed in patients with FEP in the Tohoku region of Japan. We also identified two novel missense variants of SCN11A, p.F814C and p.F1146S. To evaluate the effects of these latter two mutations, we generated knock-in mouse models harboring p.F802C (F802C) and p.F1125S (F1125S), orthologues of the human p.F814C and p.F1146S, respectively. We then performed electrophysiological investigations using dorsal root ganglion neurons dissected from the 6-8 week-old mice. Dissected neurons of F802C and F1125S mice showed increased resting membrane potentials and firing frequency of the action potentials (APs) by high input-current stimulus compared with WT mice. Furthermore, the firing probability of evoked APs increased in low stimulus input in F1125S mice, whereas several AP parameters and current threshold did not differ significantly between either of the mutations and WT mice. These results suggest a higher level of excitability in the F802C or F1125S mice than in WT, and indicate that these novel mutations are gain of function mutations. It can be expected that a considerable number of potential patients with FEP may be the result of gain of function SCN11A mutations., Competing Interests: The authors of this manuscript have read the journal’s policy and have the following competing interests: Prof. Akio Koizumi, Dr. Hatasu Kobayashi, Dr. Kouji H. Harada, Prof. Tsutomu Takahashi, Dr. Atsuko Noguchi and Dr. Daiki Kondo have a patent pending regarding with SCN11A (name of patent ‘pain gene and its applications’, Japanese Patent Application No. 2014-238250). This does not alter the authors’ adherence to PLOS genetics policies on sharing data and materials.

Refractory pleural effusion can be a life-threatening complication in patients receiving maintenance hemodialysis. We report successful treatment of refractory pleural effusion using a Denver® pleuroperitoneal shunt in one such patient. A 54-year-old Japanese man, who had previously undergone left nephrectomy, was admitted urgently to our department because of a high C-reactive protein (CRP) level, right pleural effusion, and right renal abscess. Because antibiotics proved ineffective and his general state was deteriorating, he underwent emergency insertion of a thoracic drainage tube and nephrectomy, and hemodialysis was started. Although his general state improved slowly thereafter, the pleural effusion, which was unilateral and transudative, remained refractory and therefore he needed to be on oxygenation. To control the massive pleural effusion, a pleuroperitoneal shunt was inserted. Thereafter, his respiratory condition became stable without oxygenation and he was discharged. His general condition has since been well. Although pleural effusion is a common complication of maintenance hemodialysis, few reports have documented the use of pleuroperitoneal shunt to control refractory pleural effusion. Pleuroperitoneal shunt has been advocated as an effective and low-morbidity treatment for refractory pleural effusion, and its use for some patients with recurrent pleural effusion has also been reported, without any severe complications. In the present case, pleuroperitoneal shunt improved the patient's quality of life sufficiently to allow him to be discharged home without oxygenation. Pleuroperitoneal shunt should be considered a useful treatment option for hemodialysis patients with refractory pleural effusion.

Objective: To reveal a molecular lesion in the ZC4H2 gene in a Japanese family with arthrogryposis multiplex congenita (AMC) and intellectual disability (ID), and to characterize clinical features of patients with ZC4H2 gene mutations through a literature review., Patients: The probands are male siblings. The elder brother is an 11-year-old boy who showed AMC and ID and frequent postprandial hypoglycemia since 3 years of age. The younger brother also showed AMC, ID, and subclinical postprandial hypoglycemia. The boys' mother also showed a minor malformation of the left toes., Method and Result: Using Sanger sequencing, a hemizygous one base substitution designated c.627G > C, which is predicted to substitute asparagine for lysine at amino acid residue 209 (K209N), was identified in the siblings. The mother was heterozygous for this mutation. In silico analysis predicted K209N to be a constituent of a motif required for subcellular localization of the ZC4H2 protein in the nucleus. Transient expression studies of subcellular localization in COS-7 cells showed that compared to the wild-type protein, the transport of the mutant protein into the nucleus was inhibited, thus confirming K209N as a molecular lesion in this family. The literature reviews revealed postprandial hypoglycemia as a new clinical feature that should be considered in ZC4H2 gene-mutation disorders., Conclusion: A Japanese family with AMC and ID caused by a novel ZC4H2 gene mutation was reported. Hypoglycemia should be considered one of the features in this disorder., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Thrombotic microangiopathy is caused by various conditions, but few cases secondary to trauma have been reported. We present the rare case of a patient with thrombotic microangiopathy-induced high-impact trauma with hemorrhagic shock., Case Presentation: An 86-year-old Japanese woman was transferred to our hospital after a traffic accident. A whole-body computed tomography scan revealed pelvic fractures with massive extravasation. She received a blood transfusion and emergency angiographic embolization. On post-traumatic day 1, she showed unexplained severe hemolysis, thrombocytopenia, and renal failure despite her stable condition. Disseminated intravascular coagulation was excluded because her activated partial thromboplastin time and prothrombin time-international normalized ratio were normal. Her fragmented red blood cell concentration was 28.8%. We suspected clinical thrombotic thrombocytopenic purpura and started plasma exchange. She recovered fully after the plasma exchange and was discharged on day 31. We eventually diagnosed thrombotic microangiopathy because her ADAMTS13 activity was not reduced., Conclusions: It is important to recognize the possibility that thrombotic microangiopathy may occur after severe trauma. In the critical care setting, unexplained thrombocytopenia and hemolytic anemia should be investigated to eliminate the possibility of thrombotic microangiopathy. Early plasma exchange may help to prevent unfortunate outcomes in patients with thrombotic microangiopathy following trauma.

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.

A study was conducted on the Neotropical scale insect genus Coccidella Hambleton (Hemiptera: Coccomorpha: Rhizoecidae) based on soil sample material deposited at the Hungarian Natural History Museum. Descriptions of the adult females of two new Coccidella species, i.e., Coccidella hexapora Kaydan & Konczné Benedicty, sp. n. and Coccidella kozari Kaydan & Szita, sp. n., are provided, plus a redescription and illustration of adult female of Coccidella kissbalazsi Konczné Benedicty & Kozár. An identification key and new additional locality records for the currently known Coccidella species are provided and the affinities of the new species are discussed.

Peripheral nerve injury induces neuropathic pain, which is characterized by the tactile allodynia and thermal hyperalgesia. N-type voltage-dependent Ca 2+ channel (VDCC) plays pivotal roles in the development of neuropathic pain, since mice lacking Ca v 2.2, the pore-forming subunit of N-type VDCC, show greatly reduced symptoms of both tactile allodynia and thermal hyperalgesia. Our study on gene expression profiles of the wild-type and N-type VDCC knockout (KO) spinal cord and several pain-related brain regions after spinal nerve ligation (SNL) injury revealed altered expression of genes encoding catalytic subunits of phosphatidylinositol-3 kinase (PI3K). PI3K/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling is considered to be very important for cancer development and drugs targeting the molecules in this pathway have been tested in oncology trials. In the present study, we have tested whether the changes in expression of molecules in this pathway in mice having spinal nerve injury are causally related to neuropathic pain. Our results suggest that spinal nerve injury induces activation of N-type VDCC and the following Ca 2+ entry through this channel may change the expression of genes encoding PI3K catalytic subunits (p110α and p110γ), Akt, retinoid X receptor α (RXRα) and RXRγ. Furthermore, the blockers of the molecules in this pathway are found to be effective in reducing neuropathic pain both at the spinal and at the supraspinal levels. Thus, the activation of PI3K/Akt/mTOR/peroxisome proliferator activated receptor gamma (PPARγ) pathway would be a hallmark of the induction and maintenance of neuropathic pain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Charcot-Marie-Tooth disease type 4H (CMT4H) is a rare variant of autosomal recessive hereditary neuropathy. It is caused by FGD4 mutations and characterized by early infantile onset, slowly progressive distal muscle weakness, scoliosis, and myelin outfoldings visible in nerve biopsy samples. Here, we report a 65-year-old male born to consanguineous parents, who carries a novel homozygous FGD4 c.724C>T nonsense mutation. He developed lower limb weakness in his teens, which progressed slowly and was accompanied by diplopia, bilateral hearing loss, and erectile dysfunction from his twenties. At the age of 65, he was wheelchair-bound and had mild scoliosis, bilateral ophthalmoplegia, facial muscle weakness, inner ear hearing loss, distal-dominant weakness, and sensory disturbance, but no cognitive deterioration. Magnetic resonance imaging revealed enlarged bilateral trigeminal and facial nerves. Accordingly, we believe that this mutation causes slowly progressive sensorimotor neuropathy with apparent cranial nerve involvement, thereby further expanding the clinical spectrum of CMT4H., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20-40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established., Methods: We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22)., Results: There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 ± 4.4 vs. 9.9 ± 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02)., Conclusions: In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

Purpose: Evidence for the prodromal stage of dementia with Lewy bodies (DLB) is very limited. To address this issue, we investigate the 123 I-FP-CIT SPECT measure of dopamine transporter binding finding and its clinical relevance., Methods: We enrolled subjects into a prodromal DLB group (PRD-DLB) (n = 20) and clinical DLB group (CLIN-DLB) (n = 18) and compared these groups with an Alzheimer's disease control group (AD) (n = 10). PRD-DLB was defined as patients having the non-motor symptoms associated with Lewy body disease (LBD) [i.e. REM sleep behavior disorder (RBD), olfactory dysfunction, autonomic dysfunction, and depression] and showing characteristic diffuse occipital hypometabolism in 18 F-FDG PET. CLIN-DLB was defined as patients fulfilling the established criteria of probable DLB. Striatal specific binding ratio (SBR) of 123 I-FP-CIT SPECT was used for objective group comparisons. The correlations between SBR and cognitive function (MMSE), motor symptoms (UPDRS3), and duration of LBD-associated non-motor symptoms were compared between the two DLB groups., Results: Mean SBR scores of both PRD-DLB and CLIN-DLB were significantly lower than those of AD. No correlation was found between SBR and MMSE scores. Both in the CLIN-DLB and total DLB groups, SBR scores were negatively correlated with UPDRS3 scores, whereas no correlation was found in PRD-DLB. Among the LBD-related non-motor symptoms, duration of olfactory dysfunction, and RBD demonstrated negative correlation with SBR scores in PRD-DLB., Conclusion: 123 I-FP-CIT SPECT may play a role for detecting DLB among the subjects in prodromal stage. During this stage, long-term olfactory dysfunction and/or RBD may indicate more severe degeneration of the nigro-striatal dopaminergic pathway.

Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signal-regulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERK-CREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells., (© 2017 International Federation for Cell Biology.)

Natural 12-hydroxyheptadecatrienoic acid (12-HHT) with an S configuration was synthesised by a Suzuki-Miyaura coupling of C10-C17 iodo alcohol with C1-C9 vinylborane. The iodo alcohol was synthesised by utilising Sharpless asymmetric epoxidation of the corresponding trimethylsilyl alcohol. The method yielded more than 100 mg of 12-HHT. Similarly, syntheses of 5,6-dihydro- and 14,15-dehydro derivatives of 12-HHT, known as HHD and HHTE, respectively, were completed in a stereoselective manner.

Aim: To determine characteristics of MCI that can predict whether patients will go on to develop AD or DLB., Methods: Ninety-three patients diagnosed with MCI underwent neuropsychological and neuroimaging examinations, and were followed-up for a mean of 44.9±19.3months. They were divided into four MCI subtypes (amnestic/non-amnestic MCI, single/multiple domain) according to neuropsychological findings, and into three other MCI categories (AD-type PET, DLB-type PET, and unknown-type PET) based on (18)F-fluorodeoxyglucose PET findings. Patients who were eventually diagnosed with AD, DLB, other dementia, or remained MCI were analyzed in relation to the groups to which they had initially been allocated at the MCI stage., Results: Clinical diagnosis after follow-up determined AD in 21 patients (22.6%), DLB in 12 patients (12.9%), other dementia in 2 patients (2.2%), and non-converter in 58 patients (62.3%). Amnestic single-domain MCI and AD-type PET tended to convert into AD. Amnestic multiple-domain MCI and DLB-type PET tended to convert into DLB. A few patients with AD-type PET later developed DLB, and some with DLB-type PET later developed AD., Conclusions: Predicting which type of dementia a person with MCI will later develop might be possible based on early assessment with clinical symptoms in conjunction with neuropsychological and (18)F-fluorodeoxyglucose PET findings., (Copyright © 2016. Published by Elsevier B.V.)

Oleic acid (OA) and oleates form self-assembled structures dispersible in aqueous media. Herein, the physicochemical properties of OA/oleate assemblies were characterized using fluorescent probes and Raman spectroscopy, under relatively high dilution (<100 mM of total amphiphile) at 25 °C. Anisotropy analysis using 1,6-diphenyl-1,3,5-hexatriene showed that the microviscosity of the OA/oleate assembly was highest at pH 7.5 (the pH range of 6.9-10.6 was investigated). The fluorescence spectra of 6-lauroyl-2-dimethylaminonaphthalene revealed the dehydrated environments on membrane surfaces at pH < 7.7. The pH-dependent Raman peak intensity ratios, chain torsion (S = I1124/I1096) and chain packing (R = I2850/I2930), showed local maxima, indicating the occurrence of metastable phases, such as dispersed cubic phase (pH = 7.5), vesicle (pH = 8.5), and dispersed cylindrical micelle (pH = 9.7). These results suggest that large-scale OA/oleate assemblies could possess particular membrane properties in a narrow pH region, e.g., at pH 7.5, and 9.7.

Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2'-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.

Psychophysical and neurophysiological evidence argues for neural channels in V1 selectively sensitive to intermediate hues between the cardinal axes of opponent-color space. The present study examined if these multiple-color channels are selective for other visual features analyzed by V1 such as orientation, spatial frequency, and motion direction. Using a conventional masking paradigm, we measured detection thresholds for an isoluminant grating modulated along a particular hue angle either in the presence or absence of a bandpass noise mask that varied in hue angle, orientation, spatial frequency, and motion direction. In line with previous studies, thresholds for the test grating were selectively elevated by noise masks with hue angles similar to that of the test. Hue-selective masking was substantially reduced if test and mask were oriented orthogonally or differed in spatial frequency, but thresholds remained elevated if the mask drifted in the direction opposite to that of the test. Masking also revealed components selective for hue angle, but not for orientation. The results support the notion that multiple-color channels partly involve visual units selective for orientation and spatial frequency but largely nonselective for motion direction.

Painful peripheral neuropathy has been correlated with various voltage-gated sodium channel mutations in sensory neurons. Recently Nav1.9, a voltage-gated sodium channel subtype, has been established as a genetic influence for certain peripheral pain syndromes. In this study, we performed a genetic study in six unrelated multigenerational Japanese families with episodic pain syndrome. Affected participants (n = 23) were characterized by infantile recurrent pain episodes with spontaneous mitigation around adolescence. This unique phenotype was inherited in an autosomal-dominant mode. Linkage analysis was performed for two families with 12 affected and nine unaffected members, and a single locus was identified on 3p22 (LOD score 4.32). Exome analysis (n = 14) was performed for affected and unaffected members in these two families and an additional family. Two missense variants were identified: R222H and R222S in SCN11A. Next, we generated a knock-in mouse model harboring one of the mutations (R222S). Behavioral tests (Hargreaves test and cold plate test) using R222S and wild-type C57BL/6 (WT) mice, young (8-9 weeks old; n = 10-12 for each group) and mature (36-38 weeks old; n = 5-6 for each group), showed that R222S mice were significantly (p < 0.05) more hypersensitive to hot and cold stimuli than WT mice. Electrophysiological studies using dorsal root ganglion neurons from 8-9-week-old mice showed no significant difference in resting membrane potential, but input impedance and firing frequency of evoked action potentials were significantly increased in R222S mice compared with WT mice. However, there was no significant difference among Nav1.9 (WT, R222S, and R222H)-overexpressing ND7/23 cell lines. These results suggest that our novel mutation is a gain-of-function mutation that causes infantile familial episodic pain. The mouse model developed here will be useful for drug screening for familial episodic pain syndrome associated with SCN11A mutations.

A 1,4-addition strategy using an enone and a copper reagent was studied for the synthesis of (-)-piperitylmagnolol. A MOM-protected biphenol copper reagent was added to BF3·OEt2-activated 4-isopropylcyclohexenone, whereas 1,4-addition of protected monophenol reagents possessing an allyl group was found to be unsuccessful. The allyl group was later attached to the p-,p'-diiodo-biphenol ring by Pd-catalyzed coupling with allylborate. The aforementioned iodide was synthesized using a new method for ortho-selective deiodination of o-,p-diiodophenols.

The present study is a follow-up study of 11 non-demented patients with probable rapid eye movement (REM) sleep behavior disorder (RBD) at our memory clinic. During the follow-up period (mean±SD of 46.7±6.4 months), all 11 patients exhibited cognitive decline: four (Group A) exhibited core clinical features of dementia with Lewy bodies (DLB), along with severe cognitive decline, and were subsequently diagnosed as having probable DLB; four (Group B) did not exhibit core clinical features of DLB; and the remaining three (Group C) were diagnosed as having Parkinson's disease with dementia (PDD). Positron emission tomography with fluorodeoxyglucose-F18 at baseline revealed that Groups A and B exhibited glucose hypometabolism in the occipital lobe, especially in the primary visual cortex, and Group A tended to present hypometabolism in the parieto-temporal area as well. Group C tended to present hypometabolism in the medial prefrontal area and anterior cingulate gyrus. Neuropsychological examinations indicated poor performance in verbal memory and visuoperception in all groups. This case study suggests that patterns of hypometabolism and neuropsychological examinations at baseline may be indicators of the later clinical course of probable RBD patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated cognitive dysfunction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) who present hemispheric asymmetries of cerebral metabolic rate of glucose (CMRglc) decrease on (18) F-fluorodeoxyglucose positron emission tomography., Methods: Based on the hemispheric asymmetries of CMRglc decrease in the posterior cingulate cortex, precuneus, and parietotemporal cortex, the patients were divided into three groups (a left-dominant hypometabolism group, a right-dominant hypometabolism group, and a non-dominant hypometabolism group). CMRglc decrease in the whole brain was controlled among the three groups. All the patients underwent mini-mental state examination (MMSE), Wechsler Memory Scale-Revised (WMS-R), and Wechsler Adult Intelligent Scale-Third (WAIS-III)., Results: There were no significant differences in MMSE and WAIS-III scores among the three groups. In WMS-R, the results indicated that the left-dominant group demonstrated significantly lower scores in verbal memory than the other two groups. Furthermore, the left-dominant group had a greater tendency to be diagnosed with AD rather than aMCI., Conclusions: Patients with AD and aMCI showing left-dominant hypometabolism tend to show severer impairment in verbal memory function and to be diagnosed with AD dementia., (Copyright © 2015 John Wiley & Sons, Ltd.)

A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis.

A chiral dicationic palladium complex is found to be an efficient Lewis acid catalyst for the synthesis of α-fluoromethyl-substituted tertiary alcohols using a three-component coupling reaction. The reaction transforms three simple and readily available components (terminal alkyne, arene, and fluoromethylpyruvate) to valuable chiral organofluorine compounds. This strategy is completely atom-economical and results in perfect regioselectivities and high enantioselectivities of the corresponding tertiary allylic alcohols in good to excellent yields., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Continuous observation of radioactivity ratio of (214)Bi to (214)Pb as tracers in rainwater was carried out with 15-min cyclic measurement at Nagoya, Japan, from August 2011 to July 2012 to characterise wet deposition. The ratio ranged from 0.55 to 3.82. Based on the observation and a simplified time evolution model of (214)Pb and (214)Bi radioactivities during rainwater formation, the 'age' of raindrops ranged from sub-10 to several 100 min. The age would have negative correlation to rainfall intensity, but its variation for lower rainfall intensities was quite large. Secular equilibrium of (214)Pb and (214)Bi radioactivities in cloud water with airborne radon did not hold for some rainfall events., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The catalytic asymmetric ene reaction with difluoropyruvate as an electrophile in the presence of a dicationic palladium complex is shown. This is the reliable and practical catalytic asymmetric synthesis for various α-CF2H tertiary alcohols in high yields and enantioselectivities. The reaction with isobutene can be catalyzed efficiently under solvent-free conditions with low catalyst loading (up to S/C 2000). Furthermore, difluoropyruvate is applicable to the [2 + 2] cycloaddition reaction in high yields and enantioselectivities.

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated left-dominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867 g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs., (© 2014 Japanese Society of Neuropathology.)

We examined the utility of illusory contours (ICs) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Thirty-five probable DLB patients, 35 probable AD patients controlled by age, years of education, and Mini-Mental State Examination (MMSE) score, and 30 cognitively normal subjects controlled by age and years of education underwent visuoperceptual examinations including ICs, pentagon copying in MMSE, overlapping figures, clock drawing test, cube copying, and line orientation. Four items in ICs (ICs-4) were found to be significantly impaired in DLB compared with AD, and a sensitivity and a specificity of total score of ICs-4 were 88.6% and 37.1%, respectively. When a score of ICs-4 is combined with a 10-point scaled score of pentagon copying in MMSE, a sensitivity and a specificity were 77.1% and 82.9%, respectively. The present study suggests that ICs-4 can be included in neuropsychological examinations to assess visuoperceptual impairment in DLB., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fatty acids (FAs) are known to form vesicle structures, depending on the surrounding pH conditions. In this study, we prepared vesicles by mixing FAs and a cationic surfactant, and then investigated their physicochemical properties using fluorescence spectroscopy and dielectric dispersion analysis (DDA). The assemblies formed from oleic acid (OA) and linoleic acid (LA) were modified by adding didecyldimethylammonium bromide (DDAB). The phase state of FA/DDAB mixtures was investigated with pH titration curves and turbidity measurements. The trigonal diagram of FA/ionized FA/DDAB was successfully drawn to understand the phase behaviors of FA/DDAB systems. The analysis of fluidities in the interior of the membrane with use of 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the membrane fluidities of OA/DDAB and LA/DDAB at pH 8.5 slightly decreased in proportion to the molar ratio of DDAB in FA/DDAB systems. The fluorescent probe 6-lauroyl-2-dimethylamino naphthalene (Laurdan) indicated that the LA vesicle possessed a dehydrated surface, while the OA vesicle surface was hydrated. Modification of LA vesicles with DDAB induced the hydration of membrane surfaces, whereas modification of OA vesicles by DDAB had the opposite effect. DDA analysis indicated that the membrane surfaces were hydrated in the presence of DDAB, suggesting that the surface properties of FA vesicles are tunable by DDAB modification.

We report a novel illusion whereby people perceive both congruent and incongruent hand motions as a united, single, and continuous motion of one's own hand (i.e. a sense of agency). This arises when individuals watch congruent and incongruent hand motions alternately from a first person perspective. Despite an individual knowing that s/he is not performing the motion, this illusion still can arise. Although a sense of agency might require congruency between predicted and actual movements, united motion is incongruent with predicted movement because the motion contains oscillating movement which results from switching hand movement images. This illusion offers new insights into the integration mechanism of predicted and observed movements on agency judgment. We investigated this illusion from a subjective experience point of view and from a motion response point of view.

Pediatric bipolar disorder is a severe mental illness whose pathophysiology is poorly understood and for which there is an urgent need for improved diagnosis and treatment. MR spectroscopy is a neuroimaging method capable of in vivo measurement of neurochemicals relevant to bipolar disorder neurobiology. MR spectroscopy studies of adult bipolar disorder provide consistent evidence for alterations in the glutamate system and mitochondrial function. In bipolar disorder, these 2 phenomena may be linked because 85% of glucose in the brain is consumed by glutamatergic neurotransmission and the conversion of glutamate to glutamine. The purpose of this article is to review the MR spectroscopic imaging literature in pediatric bipolar disorder, at-risk samples, and severe mood dysregulation, with a focus on the published findings that are relevant to glutamatergic and mitochondrial functioning. Potential directions for future MR spectroscopy studies of the glutamate system and mitochondrial dysfunction in pediatric bipolar disorder are discussed., (© 2014 by American Journal of Neuroradiology.)

Hypocretin (Hcrt) is a neuropeptide synthesized in the lateral hypothalamus (LHT) that plays a key role in maintaining arousal state. In Parkinson's disease (PD), a narcolepsy-like syndrome is commonly seen, and a previous study showed substantial Hcrt neuronal loss in accordance with PD severity. In the present study, we quantitatively examined Hcrt immunoreactivity and α-synuclein and tau pathologies in the LHT and locus coeruleus (LC) in dementia with Lewy bodies (DLB) (n=15), Alzheimer's disease (AD) (n=14), and controls (n=7). In the LHT, substantial Hcrt-positive neurons were detected in controls. In contrast, in DLB and AD, the numbers of both total neurons and Hcrt-positive neurons were significantly reduced. The reduction of the latter was significantly severer in DLB than in AD. In the LC of controls, many Hcrt-positive axonal terminals were found. In contrast, the amount of Hcrt immunoreactivity was significantly reduced both in DLB and AD. In DLB, some Lewy body (LB)-bearing neurons were detected in the LHT, but the Hcrt-positive neurons did not have any LBs. Meanwhile, some tau-positive neurofibrillary tangle (NFT)-bearing neurons were detected in the LHT, and Hcrt-positive neurons occasionally contained NFTs. We observed a significant negative correlation between the number of Hcrt-positive neurons in the LHT and the neurofibrillary stage (r=-0.67, p=0.0067), whereas no significant correlation was found between the number of Hcrt-positive neurons and the Lewy stage (r=-0.47, p=0.077). This is the first report clarifying the substantial loss of Hcrt neurons in the LHT and of Hcrt axonal terminals in the LC in DLB and the correlation between the severity of Hcrt neuronal loss and progression of neurofibrillary pathology., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Threonine synthase catalyzes the most complex reaction among the pyridoxal-5'-phosphate (PLP)-dependent enzymes. The important step is the addition of a water molecule to the Cβ-Cα double bond of the PLP-α-aminocrotonate aldimine intermediate. Transaldimination of this intermediate with Lys61 as a side reaction to form α-ketobutyrate competes with the normal addition reaction. We previously found that the phosphate ion released from the O-phospho-l-homoserine substrate plays a critical role in specifically promoting the normal reaction. In order to elucidate the detailed mechanism of this "product-assisted catalysis", we performed comparative QM/MM calculations with an exhaustive search for the lowest-energy-barrier reaction pathways starting from PLP-α-aminocrotonate aldimine intermediate. Satisfactory agreements with the experiment were obtained for the free energy profile and the UV/vis spectra when the PLP pyridine N1 was unprotonated and the phosphate ion was monoprotonated. Contrary to an earlier proposal, the base that abstracts a proton from the attacking water was the ε-amino group of Lys61 rather than the phosphate ion. Nevertheless, the phosphate ion is important for stabilizing the transition state of the normal transaldimination to form l-threonine by making a hydrogen bond with the hydroxy group of the l-threonine moiety. The absence of this interaction may account for the higher energy barrier of the side reaction, and explains the mechanism of the reaction specificity afforded by the phosphate ion product. Additionally, a new mechanism, in which a proton temporarily resides at the phenolate O3' of PLP, was proposed for the transaldimination process, a prerequisite step for the catalysis of all the PLP enzymes.

We report here an autopsy case of concurrent Huntington's disease (HD) and neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease. The patient was a Japanese woman with a significant hereditary burden: seven of her family members within four generations were affected by either NF1 or concurrent HD and NF1. She was diagnosed as having NF1 at age 24. At age 40, she showed signs of irritability, aggressive and childish behaviour, which became progressively worse. At age 48, rigidity and spastic gait were observed. One year later, choreoathetoid involuntary movements became apparent. Diagnosis of HD was made by identification of the abnormally expanded cytosine-adenine-guanine repeats in the Huntington's disease gene. Her condition deteriorated gradually to an apallic state and she died at age 60. Post-mortem examination revealed extensive brain atrophy, which was particularly severe in the frontal and temporal cortices and the striatum. The degree of neurodegenerative change seemed to correspond to grade IV. Polyglutamine positive inclusions were seen frequently in all layers of the cerebral cortex and in the amygdala and hippocampus. Inclusions were also present in the striatum, but there were fewer than in the cortex. Remarkably, neuronal intranuclear inclusions were present in the cerebellum, although they are usually not seen in HD. Features associated with the central nervous system involvement of NF1 were not found in the brain, but HD pathology might have been accelerated by the concurrence of NF1. This is the third report of a case with concurrent HD and NF1 in the world, and the first study in which occurrence of polyglutamine inclusions was confirmed on post-mortem examination., (© 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.)

The DNA religation reaction of yeast type II topoisomerase (topo II) was investigated to elucidate its metal-dependent general acid/base catalysis. Quantum mechanical/molecular mechanical calculations were performed for the topo II religation reaction, and the proton transfer pathway was examined. We found a substrate-mediated proton transfer of the topo II religation reaction, which involves the 3' OH nucleophile, the reactive phosphate, water, Arg781, and Tyr782. Metal A stabilizes the transition states, which is consistent with a two-metal mechanism in topo II. This pathway may be required for the cleavage/religation reaction of topo IA and II and will provide a general explanation for the catalytic mechanism in the topo IA and II.

Purpose: To evaluate the capabilities of gelatin derivatives that incorporate phenolic hydroxyl groups (gelatin-Ph) as a delivery carrier with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) for bone regeneration., Materials and Methods: The growth factor release profile from gelatin-Ph gel or atelocollagen was analyzed to evaluate the capability of gelatin-Ph as a carrier. The biocompatibility of gelatin-Ph (ie, the survival rates of the cells during gelation, and the morphology and proliferation of the cells) were investigated with rat bone marrow cells (RBMCs) in vitro. To evaluate the effect of the gelatin-Ph-rhPDGF-BB complex on bone formation, the complex was applied to bone defects in rat tibiae and undecalcified specimens were fabricated for histologic analysis., Results: Scarce amounts of rhPDGF-BB from gelatin-Ph gel were detected during 30 days, but the addition of protease induced the release of rhPDGF-BB on day 31. No differences were observed in the survival rates of RBMCs during gelation and in the morphology and proliferation of RBMCs on the gel sheet between groups. Histological analyses demonstrated that the complex enhanced bone formation and mineralization at 2 and 4 weeks., Conclusion: These results suggest that gelatin-Ph gel can be an ideal delivery carrier, and the localized delivery of rhPDGF-BB in gelatin-Ph can contribute to bone formation.

The outer membrane lipoprotein RcsF is an essential component of the Rcs phosphorelay signal transduction system in Escherichia coli. It senses stresses imposed on the cell envelope and conveys the information to histidine kinase RcsC in the cytoplasmic membrane. Mislocalization of RcsF to the periplasm, effected by fusing it to the periplasmic maltose-binding protein, or to the cytoplasmic membrane, brought about by changing the lipoprotein sorting signal, leads to high activation of the Rcs system, suggesting that RcsF functions as a ligand for RcsC in activating the system. Here, we focus on the proline-rich region (PRR) in the N-terminal half of RcsF, a region which also contains many basic amino acid residues. Deletion of the PRR in the mislocalized RcsF resulted in even higher activation of the Rcs system. The same deletion in wild-type RcsF lipoprotein that is correctly localized to the outer membrane, however, blocked activation of the system under stresses that normally should activate it. It is highly likely that the PRR plays an important role in the regulation of the function of RcsF in activating the Rcs system.

The Rcs phosphorelay signal transduction system controls genes for capsule production and many other envelope-related functions and is implicated in biofilm formation. We investigated the activation of the Rcs system in a pgsA null mutant of Escherichia coli, which completely lacks the major acidic phospholipids phosphatidylglycerol and cardiolipin. We found that the Rcs activation, and consequent thermosensitivity, were suppressed by overexpression of the lgt gene, encoding diacylglyceryltransferase, which catalyses the modification of prolipoproteins that is the first step in the maturation and localization process of lipoproteins, and is a prerequisite for the later steps. The outer-membrane lipoprotein RcsF is an essential component of Rcs signalling. This lipoprotein was poorly localized to the outer membrane in the pgsA null mutant, probably because of the absence of phosphatidylglycerol, the major donor of diacylglycerol in the Lgt reaction. Even in a pgsA(+) background, the Rcs system was activated when RcsF was mislocalized to the inner membrane by alteration of the residues at positions 2 and 3 of its mature form to inner-membrane retention signals, or when it was mislocalized to the periplasm by fusing the mature form to maltose-binding protein. These results suggest that RcsF functions as a ligand for RcsC in activating Rcs signalling. Mislocalized versions of RcsF still responded to mutations pgsA, mdoH and tolB, further activating the Rcs system, although the rfaP mutation barely caused activation. It seems that RcsF must be localized in the outer membrane to respond effectively to stimuli from outside the cell.

Sorghum shows strong growth stimulation on arbuscular mycorrhizal (AM) symbiosis, while barley and wheat show growth depression. We identified the AM-inducible phosphate transporter genes of these cereals. Their protein products play major roles in phosphate absorption from arbuscules, intracellular fungal structures. Unexpectedly, barley and wheat expressed the AM-inducible genes at high levels. Hence the cause of their growth depression appears to be unrelated to the transcription of these genes. Notably, fungal vesicles were formed significantly more in barley and wheat than in sorghum. This study yielded new clues for investigation of the mechanism underlying these various responses.

A three-year open-label study of atomoxetine in adults with ADHD followed two multicenter, double-blind trials. In the double-blind trials, female gender and higher levels of emotional symptoms were associated with better outcome. Following a 4-week placebo washout period, 384 (of 536) subjects continued into the open-label study. 61% of subjects entering this open-label study remained after 6 months at an average dose of 100 mg/day. Subjects who had previously responded to double-blind atomoxetine achieved maximum response after 8 weeks of open-label medication, but others continued to improve for 36 weeks. Women improved more (7.7 ± 6.4) than men (6.1 ± 6.4) on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) (P = .007) and the Conners' Adult ADHD Rating Scale (P = .03). Subjects with emotional dysregulation improved more than others on the WRAADDS (P = .001). Responders ultimately improved approximately 60% in attentional, hyperactive/impulsive, and emotional symptoms. Thirty-nine percent of atomoxetine double-blind non-responders became responders during open-label treatment.

Background: Major depressive disorder (MDD) is a common disorder that is often associated with suicide. We have recently suggested that elevation may play a role in regional variations in rates of suicide. We hypothesize that there is also a significant correlation between incidence of MDD and elevation of residence., Methods: The substate estimates from the 2004 to 2006 National Surveys on Drug Use and Health (NSDUH) report from SAMHSA was used to extract substate level data related to percentages of people 18 years or older who experienced serious psychological distress or a major depressive episode in the past year. Mean elevation of each substate region was calculated by averaging the weighted elevations of its relevant counties. Average elevation for United States counties was calculated using the Shuttle Radar Topography Mission (SRTM) elevation dataset. Pearson correlation coefficients were computed to investigate the association between average substate elevation and rate of serious psychological distress or major depressive episode., Results: There was a significant correlation between percentage of people experiencing serious psychological distress in the past year in a substate region and that substate region's mean elevation (r=0.18; p=0.0005), as well as between the percentage of people having at least one major depressive episode in the past year in a substate region and that substate region's mean elevation (r=0.27; p0.0001)., Conclusions: Elevation appears to be a significant risk factor for MDD. Further studies are indicated to determine whether the increased incidence of depression with increased elevation may be due to the hypoxic effects on subjects with MDD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We examined the effects of lysophosphatidic acid (LPA) on in vitro proliferation and differentiation of a porcine preadipocyte cell line, DFAT-P, and a mouse preadipocyte cell line, 3T3-L1. During the proliferation and differentiation phases, DFAT-P and 3T3-L1 cells expressed only the endothelial differentiation gene (EDG)-2 receptor and not EDG-4 and EDG-7 receptors. LPA promoted the proliferation of DFAT-P cells more extensively than that of 3T3-L1 cells. After adipogenic induction, LPA inhibited glycerol-3-phosphate dehydrogenase activity and lipid droplet accumulation, and suppressed peroxisome proliferator-activated receptor γ (PPARγ) protein expression, this inhibitory effect in DFAT-P cells was twice as high as that in 3T3-L1 cells. Furthermore, treatments with low LPA concentrations significantly inhibited adipocyte differentiation in DFAT-P cells but not in 3T3-L1 cells. We conclude that LPA promotes the proliferation of porcine preadipocytes through the EDG-2 receptor but inhibits their differentiation, and these effects depend on the down-regulation of PPARγ expression via the EDG-2 receptor. Furthermore, DFAT-P cells are more sensitive to LPA than 3T3-L1 cells. These findings in a porcine model will contribute to the understanding of LPA action mechanisms on in vitro proliferation and differentiation of preadipocytes in domestic animals and/or humans., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A room-temperature pulsed operation was demonstrated using lateral current injection-type lasers composed of a 400-nm-thick GaInAsP core layer with compressively strained 5 quantum wells. A threshold current of 105 mA and corresponding density of 1.3 kA/cm(2) (260 A/cm(2) per well) were obtained with the stripe width of 5.4 microm and the cavity length of 1.47 mm. A fundamental transverse mode operation was obtained with the narrower stripe device of 2.0 microm and the cavity length of 805 microm, while the threshold current and corresponding density were 49 mA and 3.0 kA/cm(2), respectively.

cDNA microarray analysis showed the expression of peripheral-type benzodiazepine receptor (PBR) mRNA is slightly enhanced in the spinal cord of mice with spinal nerve injury (SNL) as compared with sham-operated mice. PBR transports cholesterol to the mitochondria, where cholesterol is converted to pregnenolone. Pregnenolone is then metabolized to progesterone, an activator of progesterone receptor, and further metabolized to produce allopregnanolone and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THDOC), positive allosteric modulators and activators of the GABA(A) receptor. In the present study, we first tested whether the enhanced PBR expression is causally related to neuropathic pain, and we found that the PBR antagonist PK11195 is effective in reducing SNL-induced mechanical allodynia and thermal hyperalgesia. Next we tested whether the PK11195-induced antinociception is attributable to reduced neurosteroid synthesis, which may possibly lead to reduced activation of the progesterone receptor and/or GABA(A) receptor. We found that allopregnanolone and 3alpha,5alpha-THDOC are effective in reducing the anti-hyperalgesic effect of PK11195, suggesting a partial contribution of reduced GABA(A)-receptor activation to PK11195-induced antinociception.

Background: In 2003, the National Institute of Mental Health funded the Child and Adolescent Psychiatry Trials Network (CAPTN) under the Advanced Center for Services and Intervention Research (ACSIR) mechanism. At the time, CAPTN was believed to be both a highly innovative undertaking and a highly speculative one. One reviewer even suggested that CAPTN was "unlikely to succeed, but would be a valuable learning experience for the field.", Objective: To describe valuable lessons learned in building a clinical research network in pediatric psychiatry, including innovations intended to decrease barriers to research participation., Methods: The CAPTN Team has completed construction of the CAPTN network infrastructure, conducted a large, multi-center psychometric study of a novel adverse event reporting tool, and initiated a large antidepressant safety registry and linked pharmacogenomic study focused on severe adverse events. Specific challenges overcome included establishing structures for network organization and governance; recruiting over 150 active CAPTN participants and 15 child psychiatry training programs; developing and implementing procedures for site contracts, regulatory compliance, indemnification and malpractice coverage, human subjects protection training and IRB approval; and constructing an innovative electronic casa report form (eCRF) running on a web-based electronic data capture system; and, finally, establishing procedures for audit trail oversight requirements put forward by, among others, the Food and Drug Administration (FDA)., Conclusion: Given stable funding for network construction and maintenance, our experience demonstrates that judicious use of web-based technologies for profiling investigators, investigator training, and capturing clinical trials data, when coupled to innovative approaches to network governance, data management and site management, can reduce the costs and burden and improve the feasibility of incorporating clinical research into routine clinical practice. Having successfully achieved its initial aim of constructing a network infrastructure, CAPTN is now a capable platform for large safety registries, pharmacogenetic studies, and randomized practical clinical trials in pediatric psychiatry.

Objective: This study was conducted to compare the differences in adipocytokines and fatty acid composition between two fraction sizes of small and large cells from subcutaneous and visceral fat of mice receiving a high-fat diet (HFD)., Methods: Body weight, blood glucose and cholesterol levels, and adipocyte diameter distribution were examined. Total adipocyte fractions could be separated into the small-cell fraction (SCF) and the large-cell fraction (LCF). Adipocytokine expression, fatty acid composition and stearoyl-CoA desaturase (SCD) expression were compared between SCF and LCF., Results: In HFD mice, body weight, glucose and cholesterol levels were significantly higher than in NCD mice. The adipocyte diameter of HFD mice continuously increased throughout the feeding period regardless of the fat depot. The expression of adipocytokine genes such as angiotensinogen, plasminogen activator inhibitor-1, adipsin, leptin, TNF-alpha and adiponectin was higher in LCF than SCF. The ratio of stearic acid to the total fatty acid content was lower in SCF than LCF, whereas oleic acid composition was higher in LCF. SCD expression was higher in LCF than SCF., Conclusion: Our results indicate that large adipocytes strongly express adipocytokine genes and show high oleic acid composition via SCD upregulation. Based on these findings, the differences in fatty acid composition between adipocyte sizes may be related to adipocytokine expression., (Copyright 2009 S. Karger AG, Basel.)

When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of 18 donors exhibited a fibroblast-like morphology and sustained high proliferative activity. Flow cytometric analysis revealed that DFAT cells comprised a highly homogeneous cell population compared with that of adipose-derived stem/stromal cells (ASCs), although the cell-surface antigen profile of DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature adipocytes marker genes but retained or gained expression of mesenchymal lineage-committed marker genes such as peroxisome proliferator-activated receptor gamma (PPARgamma), RUNX2, and SOX9. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate culture conditions. DFAT cells also formed osteoid matrix when implanted subcutaneously into nude mice. In addition, clonally expanded porcine DFAT cells showed the ability to differentiate into multiple mesenchymal cell lineages. These results indicate that DFAT cells represent a type of multipotent progenitor cell. The accessibility and ease of culture of DFAT cells support their potential application for cell-based therapies., ((c) 2007 Wiley-Liss, Inc.)

Feeding conditions, competitive regime, and female social relationships of Japanese macaques (Macaca fuscata) on Yakushima were compared between the two habitats at two different altitudes (coniferous forest, 1,000-1,200 m and coastal forest, 0-200 m). Fruit availability was higher in the coastal forest. There was no consistent difference in the frequency of agonistic interactions within a group during feeding between the two habitats. The coastal forest evoked stronger inter-group contest competition compared to the coniferous forest as evidenced by a higher inter-group encounter rate and a higher proportion of aggressive encounters to non-aggressive ones. Birth rate was higher in larger groups compared to smaller ones in the coastal forest, but did not differ in the coniferous forest. In spite of these differences in competitive regime, no variation in female social relationships was observed, such as direction and concentration on particular individuals in grooming, linearity in dominance rank, counter-attack, and support of juvenile kin during agonistic interactions. The present results indicate that the female social relationships of Japanese macaques are robust and do not change according to changes in the current environment.