Gender difference in the effect of uric acid on striatal dopamine in early Parkinson's disease.

BACKGROUND AND PURPOSE: High uric acid (UA) levels have been shown to exert a neuroprotective effect in Parkinson's disease (PD) by inhibiting oxidative stress in the nigrostriatal pathway. However, the association between striatal dopamine activity and UA level has not been clarified. METHODS: A total of 213 patients with early PD were enrolled. All patients underwent positron emission tomography using 18 F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and a venous blood test for quantification of serum UA. All patients were stratified into either the lower UA group or the higher UA group using the median UA level. After normalizing the positron emission tomography images, differences in the regional standardized uptake value ratios (SUVRs) were analyzed with a volume-of-interest template. All tested SUVRs were also compared after categorizing patients by gender. RESULTS: The UA affected dopamine transporter SUVRs in different ways by gender. In female patients, the higher UA level group showed a smaller reduction in dopamine transporter uptake in the posterior putamen, whereas there was no such association observed in male patients. CONCLUSIONS: Higher UA levels were correlated with higher dopamine transporter uptake in the putamen in female patients with early PD. This finding suggests that UA has a neuroprotective effect, as demonstrated by the relatively preserved striatal dopamine activity in women.

Normal 'heart' in Parkinson's disease: is this a distinct clinical phenotype?

BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake. METHODS: Among 160 de-novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non-motor features were evaluated using questionnaires and laboratory tests. RESULTS: Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non-motor impairments. CONCLUSIONS: These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non-motor manifestations compared with PD with decreased MIBG.

Alteration by p11 of mGluR5 localization regulates depression-like behaviors.

Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.

Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P < 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available.

Expression of cubilin in mouse testes and Leydig cells.

Cubilin (cubn) is a receptor for vitamins and various protein ligands. Cubn lacks a transmembrane domain but anchors to apical membranes by forming complexes with Amnionless or Megalin. In an effort to better understand the uptake of nutrients in testis, we analysed cubn expression in the developing mice testes. In testes, cubn mRNA increased from birth to adulthood. In the inter-stitium and isolated seminiferous tubules, neonatal increase in cubn mRNA until 14 days post-partum (pp) was followed by a marked increase at puberty (28 days pp). Cubn was found in the gonocytes, spermatogonia, spermatocytes and spermatids in the developing testes. In adult testes, strong Cubn immunoreactivity was found in the elongating spermatids, suggesting the role of Cubn in endocytosis during early spermiogenesis. In Sertoli cells and peritubular cells, Cubn immunoreactivity was weak throughout the testis development. In the inter-stitium, Cubn immunoreactivity was found in foetal Leydig cells, was weak to negligible in the stem cells and progenitor Leydig cells and was strong in immature and adult Leydig cells, demonstrating a positive association between Cubn and steroidogenic activity of Leydig cells. Collectively, these results suggest that Cubn may participate in the endocytotic uptake of nutrients in germ cells and somatic cells, supporting the spermatogenesis and steroidogenesis in mouse testes.

Successive Magnetic-Field-Induced Transitions and Colossal Magnetoelectric Effect in Ni_{3}TeO_{6}.

We report the discovery of a metamagnetic phase transition in a polar antiferromagnet Ni_{3}TeO_{6} that occurs at 52 T. The new phase transition accompanies a colossal magnetoelectric effect, with a magnetic-field-induced polarization change of 0.3 µC/cm^{2}, a value that is 4 times larger than for the spin-flop transition at 9 T in the same material, and also comparable to the largest magnetically induced polarization changes observed to date. Via density-functional calculations we construct a full microscopic model that describes the data. We model the spin structures in all fields and clarify the physics behind the 52 T transition. The high-field transition involves a competition between multiple different exchange interactions which drives the polarization change through the exchange-striction mechanism. The resultant spin structure is rather counterintuitive and complex, thus providing new insights on design principles for materials with strong magnetoelectric coupling.

X-ray imaging and multiferroic coupling of cycloidal magnetic domains in ferroelectric monodomain BiFeO3.

Magnetic domains at the surface of a ferroelectric monodomain BiFeO(3) single crystal have been imaged by hard x-ray magnetic scattering. Magnetic domains up to several hundred microns in size have been observed, corresponding to cycloidal modulations of the magnetization along the wave vector k=(δ,δ,0) and symmetry equivalent directions. The rotation direction of the magnetization in all magnetic domains, determined by diffraction of circularly polarized light, was found to be unique and in agreement with predictions of a combined approach based on a spin-model complemented by relativistic density-functional simulations. Imaging of the surface shows that the largest adjacent domains display a 120° vortex structure.

Giant magnetic fluctuations at the critical endpoint in insulating HoMnO3.

Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP's) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., χ''(2.05 T,2.2 K)/χ''(3 T,2.2 K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3.

MnSb2O6: a polar magnet with a chiral crystal structure.

Structural and magnetic chiralities are found to coexist in a small group of materials in which they produce intriguing phenomenologies such as the recently discovered Skyrmion phases. Here, we describe a previously unknown manifestation of this interplay in MnSb(2)O(6), a trigonal oxide with a chiral crystal structure. Unlike all other known cases, the MnSb(2)O(6) magnetic structure is based on corotating cycloids rather than helices. The coupling to the structural chirality is provided by a magnetic axial vector, related to the so-called vector chirality. We show that this unique arrangement is the magnetic ground state of the symmetric-exchange Hamiltonian, based on ab initio theoretical calculations of the Heisenberg exchange interactions, and is stabilized by out-of-plane anisotropy. MnSb(2)O(6) is predicted to be multiferroic with a unique ferroelectric switching mechanism.

Fucosyl neoglycoprotein binds to mouse epididymal spermatozoa and inhibits sperm binding to the egg zona pellucida.

Glycan epitopes of cellular glycoconjugates act as versatile biochemical signals, and this sugar coding plays an important role in cell-to-cell recognition processes. In this study, our aims were to determine the distribution of sperm receptors with activity for fucosyl- and galactosyl glycans and to address whether monosugar neoglycoproteins functionally mimic the binding between zona pellucida (ZP) glycoproteins and spermatozoa. In mouse epididymal spermatozoa with intact acrosomes, fucopyranosyl bovine serum albumin (BSA-Fuc) bound to the segment of the acrosome, the equatorial segment, and the postacrosome region of the sperm head. Galactosyl BSA (BSA-Gal) binding activity was similar to that of BSA-Fuc, but was weaker. In acrosome-reacted spermatozoa treated with the Ca(2+) ionophore A23187, BSA-zuc binding was lost in the apical segment of the acrosome but remained in the equatorial segment and postacrosome regions. BSA-Gal binding to the equatorial region was increased. In the presence of 2.5 µg ml(-1) BSA-Fuc, in vitro sperm-ZP binding was significantly decreased, indicating that fucosyl BSA functionally mimics ZP glycoproteins during sperm-egg ZP interactions. At the same concentration, BSA-Gal was not effective. Fucosyl BSA that efficiently inhibited the sperm-ZP binding can mimic the ZP glycoconjugate and has potential for use as a sperm fertility control agent in mouse.

Charge-orbital density wave and superconductivity in the strong spin-orbit coupled IrTe2:Pd.

Using transmission electron microscopy, the anomalies in resistivity and magnetic susceptibility at ~262 K in IrTe2 are found to accompany the superlattice peaks with q[over q=(1/5,0,-1/5). The wave vector is consistent with our theoretical calculation for the Fermi surface nesting vector, indicating that the ~262 K transition is of the charge-orbital density wave (DW) type. We also discovered that both Pd intercalation and substitution induce bulk superconductivity with T(c) up to ~3 K, which competes with DW in a quantum critical pointlike manner.

Observation of a multiferroic critical end point.

The study of abrupt increases in magnetization with magnetic field known as metamagnetic transitions has opened a rich vein of new physics in itinerant electron systems, including the discovery of quantum critical end points with a marked propensity to develop new kinds of order. However, the electric analogue of the metamagnetic critical end point, a "metaelectric" critical end point, has been rarely studied. Multiferroic materials wherein magnetism and ferroelectricity are cross-coupled are ideal candidates for the exploration of this novel possibility using magnetic-field (H) as a tuning parameter. Herein, we report the discovery of a magnetic-field-induced metaelectric transition in multiferroic BiMn(2)O(5), in which the electric polarization (P) switches polarity along with a concomitant Mn spin-flop transition at a critical magnetic field H(c). The simultaneous metaelectric and spin-flop transitions become sharper upon cooling but remain a continuous cross-over even down to 0.5 K. Near the P = 0 line realized at mu(0)H(c) approximately 18 T below 20 K, the dielectric constant (epsilon) increases significantly over wide field and temperature (T) ranges. Furthermore, a characteristic power-law behavior is found in the P(H) and epsilon(H) curves at T = 0.66 K. These findings indicate that a magnetic-field-induced metaelectric critical end point is realized in BiMn(2)O(5) near zero temperature.

Expression of amnionless in mouse testes and Leydig cells.

Vitamin B(12) (cobalamin) deficiency results in atrophy of seminiferous tubules and aplasia of spermatozoa and spermatid. The transmembrane protein amnionless (AMN) directs endocytosis of cubilin with its ligand, contributing to intrinsic factor-vitamin B(12) absorption. To understand vitamin B(12) transport in testis, we analysed AMN expression in developing mouse testes and in Leydig cells and speculated the possible role of AMN in testis. In testes, Amn mRNA levels were low until 14 days post partum (pp) and markedly increased from puberty onwards. In the interstitium, Amn mRNA levels were low at 14 days pp and increased at puberty (28 days pp) together with 3-beta-hydroxysteroid dehydrogenase type 6 mRNA. Strong AMN immunoreactivity was observed in early spermatocytes from 7 days pp, suggesting that AMN participates in meiosis. In Leydig cells, AMN was not observed until 14 days pp but was strongly expressed after 28 days pp, suggesting a positive relationship between AMN expression and functional differentiation of adult Leydig cells. Together, AMN may participate in meiosis in early spermatocytes and in functional differentiation of adult Leydig cells through the mediation of vitamin B(12) transport in the mouse testes. This is the first report on AMN expression in the germ cells and soma of mammalian testes.

Butyl paraben-induced changes in DNA methylation in rat epididymal spermatozoa.

Parabens have been shown to affect male rodent reproductive parameters, including testosterone levels and sperm production. In this study, we examined the effect of long-term exposure to butyl paraben (BP) on rat epididymal sperm DNA methylation. Adult male rats were exposed to BP (0, 10, 100 and 1000 mg kg(-1) per day) according to OECD TG407 for a repeated 28-day oral toxicity study. Sperm DNA methylation was examined by differential display random amplification of polymorphic DNA (RAPD) following methylation-specific restriction digestion of DNA. Among the 57 RAPD amplicons, six were methylation specific. Of these, five amplicons increased by 1.4- to 3.8-fold in epididymal sperm DNA at testing dose of BP. This indicates that BP can cause DNA hypermethylation in germ cells from the mitotic through post-meiotic stage in adult rat testes. To our knowledge, this is the first report on the epigenetic modification of sperm DNA by parabens.

Color vision in Parkinson's disease and essential tremor.

BACKGROUND AND PURPOSE: Decreased visual function is one of the non-motor dysfunctions of Parkinson's disease (PD). Recent evidences suggest that essential tremor (ET) is not 'pure' motor disorder and there is growing evidence that this disease is a multiple-system disorder. In some cases, it is difficult to differentiate ET from PD. In addition, there is considerable controversy regarding the relationship between PD and ET. The objective of this study was to compare color discrimination dysfunction amongst patients with PD and ET and to investigate the clinical relevance. METHODS: Case-control comparisons of 54 patients with PD, 36 patients with ET, and 34 age-matched controls were performed. All cases underwent Farnsworth-Munsell 100 Hue test (FMT) and clinical assessments on medication. In addition, the association between color vision abnormalities and motor handicaps was investigated. RESULTS: There were significant differences in the total error scores (TES) of the FMT amongst the three groups; patients with the PD had higher TES than the patients with ET and the controls after adjustments for age. In addition, the motor symptom severity in PD correlated with the FMT abnormalities, especially with regard to the axial symptoms. CONCLUSION: The results of this study suggest that color vision abnormalities may be one of the non-motor clinical characteristics of PD-related dysfunction in contrast to ET. In addition, the severity of axial motor symptoms was closely related to visual dysfunction. Confirmation of these findings as well as the mechanisms underlying these results requires further study.

Alteration of ictal and interictal perfusion in patients with paroxysmal kinesigenic dyskinesia.

Although previous cerebral blood flow studies have suggested that the basal ganglia or thalamus are involved in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD), the precise anatomic substrate or pathophysiological networks associated with PKD remain unclear. Here, ictal and interictal single photon emission computed tomography (SPECT) in 2 patients with idiopathic PKD compared to 6 age-matched normal controls and the perfusion findings of subtraction ictal SPECT co-registered to MRI (SISCOM) in 1 patient are reported. The interictal and ictal perfusion changes were different in each of the patients and there were no consistent anatomic substrates observed. 2 patients had significant perfusion changes in the left frontal/temporal cortices compared to controls, whereas the others showed an increased uptake of 99mTc-ethyl cysteinate dimer (ECD) in the left occipital area on subtraction SPECT imaging. The results of this study suggest that the pathophysiology of PKD cannot be simply explained by lesions of the basal ganglia or thalamus, and that other associated areas of the cortex are likely involved in these movement disorders.

Electrical properties and surface morphology of SiO(x)-Pt nano-composite thin films.

Recently, ceramic metals (cermets) have been widely investigated for use as embedded resistor materials. In this study, SiO-Pt nano-composite cermets were developed to control the resitivity and temperature coefficients of resistance (TCR) of embedded thin film resistors. The SiO-Pt nano-composite was prepared by the co-sputtering of a SiO(x) target and Pt chips onto glass. The experiments were conducted Pt concentrations in order to find the optimum conditions to achieve a high resistivity and low TCR. The electrical properties of the sputtered SiO-Pt thin films were investigated by probe station and their crystal structures were observed by X-Ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). The surface morphology was observed by field emission scanning electron microscopy (FE-SEM) and high resolution transmission electron microscopy (HR-TEM). It was found that the Pt particles with a size of 3 approximately 5 nm were uniformly dispersed in the SiO matrix. A stable resistivity value of 26000 approximately 57000 microomega x cm and TCR value of -197 approximately -322 ppm/K were obtained at 3.5 approximately 3.7 at.% Pt.

Selective multi-nanosoldering for fabrication of advanced solution-processed micro/nanoscale metal grid structures.

Solution-processed metal grid transparent conductors with low sheet resistance, high optical transmittance and good mechanical flexibility have great potential for use in flexible optoelectronic devices. However, there are still remaining challenges to improve optoelectrical properties and electromechanical stability of the metallic structures due to random loose packings of nanoparticles and the existence of many pores. Here we introduce a selective multi-nanosoldering method to generate robust metallic layers on the thin metal grid structures (< a thickness of 200 nm), which are generated via self-pining assisted direct inking of silver ions. The selective multi-nanosoldering leads to lowering the sheet resistance of the metal grid transparent conductors, while keeping the optical transmittance constant. Also, it reinforces the electromechanical stability of flexible metal grid transparent conductors against a small bending radius or a repeated loading. Finally, organic light-emitting diodes based on the flexible metal grid transparent conductors are demonstrated. Our approach can open a new route to enhance the functionality of metallic structures fabricated using a variety of solution-processed metal patterning methods for next-generation optoelectronic and micro/nanoelectronic applications.

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis.

Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H(2)O(2), staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH(2)-terminal kinase (JNK) inhibitor, restored the level of Bcl-2 protein. Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway.