Long-term feeding of hydroalcoholic extract powder of Lepidium meyenii (maca) enhances the steroidogenic ability of Leydig cells to alleviate its decline with ageing in male rats.

This study examined whether feeding hydroalcoholic extract of Lepidium meyenii (maca) to 8-week-old (sexually maturing) or 18-week-old (mature) male rats for more than a half year affects serum testosterone concentration and testosterone production by Leydig cells cultured with hCG, 22R-hydroxycholesterol or pregnenolone. Testosterone concentration was determined in the serum samples obtained before and 6, 12, 18 and 24 weeks after the feeding, and it was significantly increased only at the 6 weeks in the group fed with the maca extract to maturing rats when it was compared with controls. Testosterone production by Leydig cells significantly increased when cultured with hCG by feeding the maca extract to maturing rats for 27 weeks (35 weeks of age) and when cultured with 22R-hydroxycholesterol by feeding it to mature rats for 30 weeks (48 weeks of age). Overall testosterone production by cultured Leydig cells decreased to about a half from 35 to 48 weeks of age. These results suggest that feeding the maca extract for a long time to male rats may enhance the steroidogenic ability of Leydig cells to alleviate its decline with ageing, whereas it may cause only a transient increase in blood testosterone concentration in sexually maturing male rats.

Treatment with the MAPK kinase inhibitor U0126 during the first two hours of in vitro maturation improves bovine oocyte developmental competence.

This study examined the effects of treatment with U0126, which inhibits MAPK by inhibiting MAPK kinase, during the first 2 hr of in vitro maturation on bovine developmental competence and on gap junction (GAPJ) communication between the oocyte and cumulus cells. The percentage of oocytes developing to the blastocyst stage in the group treated with 5 µM U0126 (28%) was significantly higher than that in controls (15%, p < .05), while that in the group treated with 10 µM U0126 (18%) was not. Breakdown of the GAPJs was delayed in the group treated with 5 µM U0126 when compared to controls, as estimated by immunohistochemical examination of connexin 43, which is a primary constituent of the GAPJs. These results indicate that treatment with 5 µM U0126 during in vitro maturation delays GAPJ breakdown and improves bovine oocyte developmental competence.

Factors related to continuous and discontinuous attendance at memory clinics.

BACKGROUND AND PURPOSE: Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. METHODS: Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). RESULTS: The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 ± 2.4 years (UH, 2.8 ± 3.0; LH, 1.5 ± 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients (P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). CONCLUSIONS: We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia.

Dissecting the structural basis for the intracellular delivery of OSW-1 by fluorescent probes.

The structural basis for the intracellular delivery of OSW-1 is investigated using fluorescent derivatives of OSW-1 and its closely related congeners. Despite the large differences in activity, all the fluorescent probes are found to translocate across the plasma membrane to the ER and Golgi apparatus. This observation suggests that the glycosylated cholestane moiety plays an important role in the cell internalization and intracellular localization property of OSW-1.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) enhances testicular gene expression of 3ß-hydroxysteroid dehydrogenase in rats.

Although feeding diets containing the extract powder of Lepidium meyenii (maca), a plant growing in Peru's Central Andes, increases serum testosterone concentration associated with enhanced ability of testosterone production by Leydig cells in male rats, changes in testicular steroidogenesis-related factors by the maca treatment are not known. This study examined the effects of maca on testicular gene expressions for luteinizing hormone receptor, steroidogenic acute regulatory protein and steroidogenic enzymes. Eight-week-old male rats were given the diets with or without (control) the maca extract powder (2%) for 6 weeks, and mRNA levels were determined by reverse transcription quantitative real-time PCR. The results showed that the testicular mRNA level of HSD3B1 (3ß-hydroxysteroid dehydrogenase; 3ß-HSD) increased by the treatment, whereas the levels of the other factors examined did not change. These results suggest that increased expression of 3ß-HSD gene may be involved in the enhanced steroidogenic ability by the maca treatment in rat testes.

Possible mechanism of BN fullerene formation from a boron cluster: Density-functional tight-binding molecular dynamics simulations.

We simulate the formation of a BN fullerene from an amorphous B cluster at 2000 K by quantum mechanical molecular dynamics based on the density-functional tight-binding method. We run 30 trajectories 200 ps in length, where N atoms are supplied around the target cluster, which is initially an amorphous B36 cluster. Most of the incident N atoms are promptly incorporated into the target cluster to form B-N-B bridges or NB3 pyramidal local substructures. BN fullerene formation is initiated by alternating BN ring condensation. Spontaneous atomic rearrangement and N2 dissociation lead to the construction of an sp(2) single-shelled structure, during which the BN cluster undergoes a transition from a liquid-like to a solid-like state. Continual atomic rearrangement and sporadic N2 dissociation decrease the number of defective rings in the BN cluster and increase the number of six-membered rings, forming a more regular shell structure. The number of four-membered rings tends to remain constant, and contributes to more ordered isolated-tetragon-rule ring placement.

Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome.

BACKGROUND AND PURPOSE: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. METHODS: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. RESULTS: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score-Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. CONCLUSIONS: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

'PrP systemic deposition disease': clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178.

BACKGROUND AND PURPOSE: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. METHODS: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). RESULTS: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. CONCLUSION: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.

Feeding hydroalcoholic extract powder of Lepidium meyenii (maca) increases serum testosterone concentration and enhances steroidogenic ability of Leydig cells in male rats.

Although Lepidium meyenii (maca), a plant growing in Peru's central Andes, has been traditionally used for enhancing fertility and reproductive performance in domestic animals and human beings, effects of maca on reproductive organs are still unclear. This study examined whether feeding the hydroalcoholic extract powder of maca for 6 weeks affects weight of the reproductive organs, serum concentrations of testosterone and luteinising hormone (LH), number and cytoplasmic area of immunohistochemically stained Leydig cells, and steroidogenesis of cultured Leydig cells in 8-week-old male rats. Feeding the extract powder increased weight of seminal vesicles, serum testosterone level and cytoplasmic area of Leydig cells when compared with controls. Weight of prostate gland, serum LH concentration and number of Leydig cells were not affected by the maca treatment. The testosterone production by Leydig cells significantly increased when cultured with 22R-hydroxycholesterol or pregnenolone and tended to increase when cultured with hCG by feeding the extract powder. The results show that feeding the hydroalcoholic extract powder of maca for 6 weeks increases serum testosterone concentration associated with seminal vesicle stimulation in male rats, and this increase in testosterone level may be related to the enhanced ability of testosterone production by Leydig cells especially in the metabolic process following cholesterol.

Characterization of primary structure and tissue expression profile of the chicken apical sodium-dependent bile acid transporter mRNA.

The ileal apical sodium-dependent bile acid cotransporter (ASBT) plays an essential role in the absorption of bile acids from intestinal lumina. ASBT cDNA has been cloned from mammalian and fish species, and the primary structure of the protein and expression properties of the mRNA have been characterized. In this study, we identified chicken ASBT mRNA by cDNA cloning. Chicken ASBT cDNA consisted of 91 bp of the 5'-untranslated region, 1,083 bp of the coding region, and 1,896 bp of the 3'-untranslated region. The cDNA encoded a protein of 360 amino acids showing significant sequence identity with mammalian and fish ASBT. The amino acid residues known to participate in the functions of mammalian ASBT were conserved in chicken ASBT. Real-time polymerase chain reaction analysis revealed that chicken ASBT mRNA was expressed at markedly higher levels in the ileum and proximal colon/rectum, relatively lower levels in the kidney, and very low levels in the jejunum and cecum. Expression levels in the ileum markedly increased after hatching, reached the highest levels on day 7 posthatching, and then decreased to adult levels. A similar expression pattern was observed in the proximal colon/rectum except for the significant decrease from day 7 posthatching to day 21 posthatching. These results suggest that chicken ASBT functions as a bile acid transporter in the ileum and proximal colon/rectum, particularly during the early posthatching period.

Order, criticality, and excitations in the extended Falicov-Kimball model.

Using exact numerical techniques, we investigate the nature of excitonic (electron-hole) bound states and the development of exciton coherence in the one-dimensional half-filled extended Falicov-Kimball model. The ground-state phase diagram of the model exhibits, besides band-insulator and staggered orbital ordered phases, an excitonic insulator (EI) with power-law correlations. The criticality of the EI state shows up in the von Neumann entropy. The anomalous spectral function and condensation amplitude provide the binding energy and coherence length of the electron-hole pairs which, on their part, point towards a Coulomb interaction driven crossover from BCS-like electron-hole pairing fluctuations to tightly bound excitons. We show that while a mass imbalance between electrons and holes does not affect the location of the BCS-BEC crossover regime, it favors staggered orbital ordering to the disadvantage of the EI. Within the Bose-Einstein condensation (BEC) regime, the quasiparticle dispersion develops a flat valence-band top, in accord with the experimental finding for Ta2NiSe5.

Frequency of HER2 expression of circulating tumour cells in patients with metastatic or recurrent gastrointestinal cancer.

BACKGROUND: The clinical significance of circulating tumour cell (CTC) detection in gastrointestinal (GI) cancer remains controversial and the molecular biological characteristics of CTCs are poorly understood. METHODS: A total of 87 patients with metastatic or recurrent GI cancer were prospectively enrolled. Circulating tumour cells and their HER2 status were assessed using the CellSearch System. RESULTS: Among the 62 CTC-positive cases, we found 22 discordant cases (35.5%). Among the HER2-negative primary tumours, 17 of 54 developed HER2-positive CTCs. Five of eight had HER2-negative CTCs among the HER2-positive primary tumours. CONCLUSION: The findings in the current study suggest that it is critical to evaluate the HER2 status of not only the primary tumour but also the CTCs because the metastasising tumour cells are the primary target of systemic therapy.

Changes in expression levels of neurotensin precursor and receptor mRNA in chicken intestinal tissues and liver during late embryonic and early posthatching development.

Neurotensin is a tridecapeptide that has multiple functions as a neurotransmitter and as a circulating hormone. Neurotensin and its related peptide, LANT6, have been isolated in the chicken, but the mRNA encoding these peptides has not been identified. In this study, we first cloned the cDNA for the chicken neurotensin precursor mRNA from the duodenum and characterized its primary structure and then investigated tissue expression patterns of neurotensin precursor and receptor mRNA. The cDNA encoded a protein of 495 amino acids that contains the sequences of chicken neurotensin and LANT6 in the C-terminal region. Real-time PCR analysis showed that the neurotensin precursor mRNA is preferentially expressed in intestinal tissues, such as the duodenum, jejunum, ileum, and colon/rectum, with temporal increases during the hatching period. The expression levels of neurotensin receptor 1 mRNA were relatively higher during the late embryonic period compared with the posthatching period in the duodenum and jejunum, whereas the expression levels were higher in the colon/rectum during the posthatching period. In the liver, the expression levels of neurotensin receptor 1 were markedly increased during the early posthatching period. These results suggest that chicken neurotensin is involved in the regulation of gastrointestinal and hepatic functions, especially during the hatching period.

Non-targeted analyses of animal plasma: betaine and choline represent the nutritional and metabolic status.

Simple liquid chromatography-mass spectrometry (LC-MS) was applied to non-targeted metabolic analyses to discover new metabolic markers in animal plasma. Principle component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) were used to analyse LC-MS multivariate data. PCA clearly generated two separate clusters for artificially induced diabetic mice and healthy control mice. PLS-DA of time-course changes in plasma metabolites of chicks after feeding generated three clusters (pre- and immediately after feeding, 0.5-3 h after feeding and 4 h after feeding). Two separate clusters were also generated for plasma metabolites of pregnant Angus heifers with differing live-weight change profiles (gaining or losing). The accompanying PLS-DA loading plot detailed the metabolites that contribute the most to the cluster separation. In each case, the same highly hydrophilic metabolite was strongly correlated to the group separation. The metabolite was identified as betaine by LC-MS/MS. This result indicates that betaine and its metabolic precursor, choline, may be useful biomarkers to evaluate the nutritional and metabolic status of animals.

Double exchange ferromagnetism in the Peierls insulator state.

We study the effects of opening the band gap on the double exchange ferromagnetism. Applying the density-matrix renormalization group method and an analytical expansion from the dimer limit to the one-dimensional double exchange model, we demonstrate for a relevant region of the exchange coupling that, in the weak dimerization regime, the Peierls gap opens in the fully spin-polarized conduction band without affecting its ferromagnetism, whereas in the strong dimerization regime, the ferromagnetism is destroyed, and the Mott gap opens instead, leading the system to the antiferromagnetic quasi-long-range order. An insulator version of double exchange ferromagnetism is thus established.

Cognitive and affective impairments of a novel SCA/MND crossroad mutation Asidan.

BACKGROUND: A variety of hereditary spinocerebellar ataxia (SCA) develops a broad spectrum of both ataxia and non-ataxia symptoms. Cognitive and affective changes are one such non-ataxia symptoms, but have been described only in hereditary SCAs with exonic CAG gene expansion. METHODS: We newly found intronic hexanucleotide GGCCTG gene expansion in NOP56 gene as the causative mutation (=SCA36) in nine unrelated Japanese familial SCA originating from Asida river area in the western part of Japan, thus nicknamed Asidan for this mutation. These patients show unique clinical balance of cerebellar ataxia and motor neuron disease (MND), locating on the crossroad of these two diseases. In the nine families, 14 patients were clinically examined and genetically confirmed to Asidan. In the present study, we examined cognitive and affective analyses on 12 patients (seven men and five women) who agreed to join the examination with average age at onset of 53.1 ± 3.2 years, average duration of 12.1 ± 5.2 years, and current average age at 65.1 ± 6.2 years. RESULTS: The 12 Asidan patients demonstrated a significant decrease in their frontal executive functions measured by frontal assessment battery (FAB) and Montreal cognitive assessment (MoCA) compared with age- and gender-matched controls, whilst mini-mental state examination (MMSE) and Hasegawa dementia score-revised (HDS-R) were within normal range. The decline of frontal executive function was related to their disease duration and scale for the assessment and rating of ataxias (SARA). They also demonstrated mild depression and apathy. Single-photon emission tomography (SPECT) analysis showed that these Asidan patients showed decline of regional cerebral blood flow (rCBF) in a particular areas of cerebral cortices such as Brodmann areas 24 and 44-46. CONCLUSION: These data suggest that the patients with Asidan mutation show unique cognitive and affective characteristics different from other hereditary SCAs with exonal CAG expansion or MND.

Peierls mechanism of the metal-insulator transition in ferromagnetic hollandite K2Cr8O16.

Synchrotron x-ray diffraction experiment shows that the metal-insulator transition occurring in a ferromagnetic state of a hollandite K(2)Cr(8)O(16) is accompanied by a structural distortion from the tetragonal I4/m to monoclinic P112(1)/a phase with a √2×√2×1 supercell. Detailed electronic structure calculations demonstrate that the metal-insulator transition is caused by a Peierls instability in the quasi-one-dimensional column structure made of four coupled Cr-O chains running in the c direction, leading to the formation of tetramers of Cr ions below the transition temperature. This provides a rare example of the Peierls transition of fully spin-polarized electron systems.

The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin.

Rho GTPases control actin reorganization and many other cellular functions. Guanine nucleotide-exchange factors (GEFs) activate Rho GTPases by promoting their exchange of GDP for GTP. Trio is a unique Rho GEF, because it has separate GEF domains, GEFD1 and GEFD2, that control the GTPases RhoG/Rac1 and RhoA, respectively. Dbl-homology (DH) domains that are common to GEFs catalyse nucleotide exchange, and pleckstrin-homology (PH) domains localize Rho GEFs near their downstream targets. Here we show that Trio GEFD1 interacts through its PH domain with the actin-filament-crosslinking protein filamin, and localizes with endogenous filamin in HeLa cells. Trio GEFD1 induces actin-based ruffling in filamin-expressing, but not filamin-deficient, cells and in cells transfected with a filamin construct that lacks the Trio-binding domain. In addition, Trio GEFD1 exchange activity is not affected by filamin binding. Our results indicate that filamin, as a molecular target of Trio, may be a scaffold for the spatial organization of Rho-GTPase-mediated signalling pathways.

Effects of metformin on plasma concentrations of glucose and mannose, G6Pase and PEPCK activity, and mRNA expression in the liver and kidney of chickens.

1. The objective of this study was to determine the effects of the gluconeogenesis inhibitor metformin on 21-d old chickens. The following parameters were measured in the liver and kidney: plasma glucose, plasma mannose, enzyme activities and mRNA expression levels of glucose-6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK). 2. Chickens were divided into two groups, and received either metformin (300 mg/kg body weight) or water. Plasma glucose and mannose concentrations were analysed by high performance liquid chromatography (HPLC). G6Pase and PEPCK activities were determined by glucose 6-phosphate and malic acid substrate methods, respectively. The expression levels of mRNA were determined by real-time PCR. 3. Plasma glucose and mannose reached their lowest concentrations 1 h after metformin administration. At 0·5 h-1 h after metformin administration, the enzyme activities and mRNA expression levels of G6Pase and PEPCK reached their lowest point in the kidney and their highest point in the liver. The decrease observed in the kidney may have been associated with reductions in both plasma glucose and mannose concentrations. 4. In conclusion, the effect of metformin on the kidney of chickens is similar to its effect in mammals. In contrast, no suppression of enzyme activity or mRNA expression was observed in chicken liver. Therefore, the mode of action of metformin, via AMPK activation, may be different in the chicken liver.