Chinese Herbal Medicine Glycyrrhiza inflataReduces Aß Aggregation and Exerts Neuroprotection through Anti-Oxidation and Anti-Inflammation.

Amyloid [Formula: see text] (A[Formula: see text]) plays a major role in the pathogenesis of Alzheimer's disease (AD). The accumulation of misfolded A[Formula: see text] causes oxidative and inflammatory damage leading to apoptotic cell death. Chinese herbal medicine (CHM) has been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of CHM extract Glycyrrhiza inflata (G. inflata) and its active constituents, licochalcone A and liquiritigenin in AD. We examined A[Formula: see text] aggregation inhibition, anti-oxidation and neuroprotection in Tet-On A[Formula: see text]-GFP 293/SH-SY5Y cells and anti-inflammatory potential in lipopolysaccharide (LPS)-stimulated RAW 264.7 and LPS and interferon (IFN)-[Formula: see text] (LPS/IFN-[Formula: see text])-activated BV-2 cells. In addition, we applied conditioned media (CM) of BV-2 cells primed with LPS/IFN-[Formula: see text] to A[Formula: see text]-GFP SH-SY5Y cells to uncover the neuroprotective mechanisms. Our results showed that G. inflata extract and its two constituents displayed potentials of A[Formula: see text] aggregation inhibition and radical-scavenging in biochemical assays, A[Formula: see text] misfolding inhibition and reactive oxygen species (ROS) reduction in A[Formula: see text]-GFP 293 cells, as well as neurite outgrowth promotion, acetylcholinesterase inhibition and SOD2 up-regulation in A[Formula: see text]-GFP SH-SY5Y cells. Meanwhile, both G. inflata extract and its constituents suppressed NO, TNF-[Formula: see text], IL-1[Formula: see text], PGE2 and/or Iba1 productions in inflammation-stimulated RAW 264.7 or BV-2 cells. G. inflata extract and its constituents further protected A[Formula: see text]-GFP SH-SY5Y cells from BV-2 CM-induced cell death by ameliorating reduced BCL2 and attenuating increased IGFBP2, cleaved CASP3, BAD and BAX. Collectively, G. inflata extract, licochalcone A and liquiritigenin display neuroprotection through exerting anti-oxidative and anti-inflammatory activities to suppress neuronal apoptosis.

Visuomotor adaptability in older adults with mild cognitive decline.

The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation.

Medicinal herbs Oenanthe javanica (Blume) DC., Casuarina equisetifolia L. and Sorghum bicolor (L.) Moench protect human cells from MPP+ damage via inducing FBXO7 expression.

BACKGROUND: The F-box protein 7 (FBXO7) mutations have been identified in families with early-onset parkinsonism and pyramidal tract signs, and designated as PARK15. In addition, FBXO7 mutations were found in typical and young onset Parkinson's disease (PD). Evidence has also shown that FBXO7 plays an important role in the development of dopaminergic neurons and increased stability and overexpression of FBXO7 may be beneficial to PD. PURPOSE: We screened extracts of medicinal herbs to enhance FBXO7 expression for neuroprotection in MPP+-treated cells. METHODS: Promoter reporter assay in HEK-293 cells was used to examine the cis/trans elements controlling FBXO7 expression and to screen extracts of medicinal herbs enhancing FBXO7 expression. MTT assay was performed to assess cell viability of MPP+-treated HEK-293/SH-SY5Y cells. In addition, proteasome activity, mitochondrial membrane potential and FBXO7/TRAF2/GATA2 protein expression were evaluated. RESULTS: We demonstrated that -202--57 region of the FBXO7 promoter is likely to contain sequences that are bound by positive trans protein factors to activate FBXO7 expression and GATA2 is the main trans protein factor enhancing FBXO7 expression. Extracts of medicinal herbs Oenanthe javanica (Blume) DC. (Umbelliferae), Casuarina equisetifolia L. (Casuarinaceae), and Sorghum bicolor (L.) Moench (Gramineae) improved cell viability of both MPP+-treated HEK-293 and SH-SY5Y cells, rescued proteasome activity in MPP+-treated HEK-293 cells, and restored mitochondrial membrane potential in MPP+-treated SH-SY5Y cells. These protection effects of herbal extracts are acting through enhancing FBXO7 and decreasing TRAF2 expression, which is probably mediated by GATA2 induction. CONCLUSION: Collectively, our study provides new targets, FBXO7 and its regulator GATA2, for the development of potential treatments of PD.

The potential of synthetic indolylquinoline derivatives for Aß aggregation reduction by chemical chaperone activity.

Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular ß-amyloid (Aß) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Aß deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Aß aggregate reducers could be effective for AD treatment. Using a Trx-His-Aß biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Aß aggregation. Treating Tet-On Aß-GFP 293 cells with these compounds reduced Aß aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Aß-GFP SH-SY5Y cells. Furthermore, treatment with above compounds improved neuronal cell viability, neurite outgrowth, and synaptophysin expression level in mouse hippocampal primary culture under oligomeric Aß-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Aß-induced inhibition of hippocampal long-term potentiation in mouse hippocampal slices. Our results demonstrate how synthetic indolylquinoline compounds are likely to work as chemical chaperones in Aß-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment.

Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in Cell Models of Spinocerebellar Ataxia 3.

Trehalose, a chemical chaperone and mTOR-independent autophagy enhancer, has shown promise in models of Huntington's disease, Parkinson's disease and tauopathies. In this study, two trehalase analogs, lactulose and melibiose, were examined for their potentials in spinocerebellar ataxia treatment. Using a SCA3 ATXN3/Q75-GFP cell model, we found that the ATXN3/Q75 aggregation was significantly prohibited by lactulose and melibiose because of their abilities to up-regulate autophagy. Meanwhile, lactulose and melibiose reduced reactive oxygen species production in ATXN3/Q75 cells. Both of them further inhibited the ATXN3/Q75 aggregation in neuronally differentiated SH-SY5Y cells. These findings suggest the therapeutic applications of novel trehalose analogs in polyglutamine aggregation-associated neurodegenerative diseases.

Error Argumentation Enhance Adaptability in Adults With Low Motor Ability.

The authors focused on young adults with varying degrees of motor difficulties and examined their adaptability in a visuomotor adaptation task where the visual feedback of participants' movement error was presented with either 1:1 ratio (i.e., regular feedback schedule) or 1:2 ratio (i.e., enhanced feedback schedule). Within-subject design was used with two feedback schedules counter-balanced and separated for 10 days. Results revealed that participants with greater motor difficulties showed less adaptability than those with normal motor abilities in the regular feedback schedule; however, all participants demonstrated similar level of adaptability in the enhanced feedback schedule. The results suggest that error argumentation enhances adaptability in adults with low motor ability.

FBXO7 Y52C polymorphism as a potential protective factor in Parkinson's disease.

Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤ 50) and only two known variants, Y52C (c.155A>G) and M115I (c.345G>A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese.

Circadian regulation of permethrin susceptibility by glutathione S-transferase (BgGSTD1) in the German cockroach (Blattella germanica).

The daily susceptibility rhythm to permethrin and the expression level of the delta class glutathione S-transferase (BgGSTD1) gene were investigated in Blattella germanica. Male cockroaches were exposed to the same concentration of permethrin at different times in a light-dark cycle, and results showed that the highest resistance occurred at night. Furthermore, the circadian rhythmicity of permethrin susceptibility was demonstrated by the highest resistance at subjective night under constant darkness. The mRNA level of the BgGSTD1 gene in the fat body of B. germanica peaked early in the day or subjective day under light-dark or constant dark conditions, whereas enzyme activity of cytosolic GSTs did not reflect the rhythmic pattern as well as BgGSTD1 expression. RNA interference (RNAi) was employed to study the function of BgGSTD1 in the circadian rhythm of permethrin susceptibility in B. germanica. Both BgGSTD1 mRNA level and cytosolic GSTs activity were significantly decreased by dsGSTD1 injection. In addition, survival of B. germanica with silenced BgGSTD1 was significantly decreased at night but not in the day when the cockroaches were exposed to permethrin. Total cytosolic GSTs activity demonstrated that is not the only gene involved in the circadian regulation of the permethrin resistance, although it is one of the major regulators of permethrin resistance.

Examining the relationship between motor assessments and handwriting consistency in children with and without probable developmental coordination disorder.

Children with Developmental Coordination Disorder (DCD) often experience difficulties in handwriting. The current study examined the relationships between three motor assessments and the spatial and temporal consistency of handwriting. Twelve children with probable DCD and 29 children from 7 to 12 years who were typically developing wrote the lowercase letters "e" and "l" in cursive and printed forms repetitively on a digitizing tablet. Three behavioral assessments, including the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), the Minnesota Handwriting Assessment (MHA) and the Movement Assessment Battery for Children (MABC), were administered. Children with probable DCD had low scores on the VMI, MABC and MHA and showed high temporal, not spatial, variability in the letter-writing task. Their MABC scores related to temporal consistency in all handwriting conditions, and the Legibility scores in their MHA correlated with temporal consistency in cursive "e" and printed "l". It appears that children with probable DCD have prominent difficulties on the temporal aspect of handwriting. While the MHA is a good product-oriented assessment for measuring handwriting deficits, the MABC shows promise as a good assessment for capturing the temporal process of handwriting in children with DCD.

Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson's disease is associated with loss of Mg2+ efflux function.

BACKGROUND: Sequence variants in SLC41A1 have been reported to be associated with Parkinson's disease (PD). This study investigates whether the genetic variants in SLC41A1 contribute to Taiwanese PD. METHODS: We sequenced SLC41A1 cDNA fragments from 80 patients with early onset PD. A cohort of PD and ethnically matched controls were examined for the sequence variant. The effect of variation on Mg(2+) homeostasis was further examined using stably induced 293 cells expressing recombinant wild type and variant SLC41A1. RESULTS: A novel heterozygous R244H in the SLC41A1 gene was identified in one early onset PD patient, which not present either in 479 PD patients or 525 normal controls with age onset >50. Both wild type and R244H SLC41A1-V5-His proteins were co-localized to areas of the plasma membrane that were stained using wheat germ agglutinin (WGA). Fluorescent probe mag-fluo-4 staining indicated that R244H SLC41A1 is dysfunctional in Mg(2+) efflux. CONCLUSIONS: This study has shown loss of Mg(2+) efflux function consequent to SLC41A1 R244H variant and SLC41A1 coding variants seem to be rare in Taiwanese PD.

Lifespan differences in cortico-striatal resting state connectivity.

Distinctive cortico-striatal circuits that serve motor and cognitive functions have been recently mapped based on resting state connectivity. It has been reported that age differences in cortico-striatal connectivity relate to cognitive declines in aging. Moreover, children in their early teens (i.e., youth) already show mature motor network patterns while their cognitive networks are still developing. In the current study, we examined age differences in the frontal-striatal "cognitive" and "motor" circuits in children and adolescence, young adults (YAs), and older adults (OAs). We predicted that the strength of the "cognitive" frontal-striatal circuits would follow an inverted "U" pattern across age; children and OAs would have weaker connectivity than YAs. However, we predicted that the "motor" circuits would show less variation in connectivity strength across the lifespan. We found that most areas in both the "cognitive" and "motor" circuits showed higher connectivity in YAs than children and OAs, suggesting general inverted "U"-shaped changes across the lifespan for both the cognitive and motor frontal-striatal networks.

HTRA2 variations in Taiwanese Parkinson's disease.

Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50 years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.

ADHD-related symptoms, emotional/behavioral problems, and physical conditions in Taiwanese children with epilepsy.

BACKGROUND/PURPOSE: Little is known about whether Asian children with epilepsy have more attention-deficit hyperactivity disorder (ADHD)-related symptoms, emotional/ behavioral problems, and physical conditions compared with those described in Western studies. The authors investigated the rates of ADHD-related symptoms, emotional/behavioral problems, and physical conditions among pediatric patients with epilepsy. METHODS: We recruited 61 patients with epilepsy, aged 6-16 years, and 122 age-, sex-, and parental education-matched school controls. Data on demographics, parental reports on the Child Behavior Checklist (CBCL) and Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), and medical records were collected. RESULTS: The average full-scale intelligence quotient of the case group was 95.8. There were 11 (18.0%), 7 (11.5%), 26 (42.6%), and 26 (42.6%) of children with epilepsy ever clinically diagnosed with developmental delay, overt ADHD symptoms, allergies reported by physicians, and behavior problems measured by the CBCL, respectively. Those children with epilepsy had more severe ADHD-related symptoms and a wider range of emotional/behavioral problems than controls (Cohen's d 0.36-0.80). The rate of potential cases of ADHD among children with epilepsy was 24.6%. A history of developmental delay predicted ADHD- related symptoms and internalizing and externalizing problems. Among children with epilepsy, a longer duration of treatment with antiepileptic drugs predicted externalizing problems, and an earlier onset of epilepsy predicted inattention and hyperactivity/impulsivity. CONCLUSION: Our findings imply that clinicians should assess physical and emotional/behavioral problems among children with epilepsy in order to provide interventions to offset possible adverse psychiatric outcomes.

Motor skill learning in children with Developmental Coordination Disorder.

Children with Developmental Coordination Disorder (DCD) are characterized as having motor difficulties and learning impairment that may last well into adolescence and adulthood. Although behavioral deficits have been identified in many domains such as visuo-spatial processing, kinesthetic perception, and cross-modal sensory integration, recent studies suggested that the functional impairment of certain brain areas, such as cerebellum and basal ganglia, are the underlying causes of DCD. This review focuses on the "motor learning deficits" in DCD and their possible neural correlates. It presents recent evidence from both behavioral and neuroimaging studies and discusses dominant neural hypotheses in DCD. Given the heterogeneity of this disorder, a successful intervention program should target the specific deficits on an individual basis. Future neuroimaging studies are critical steps in enhancing our understanding of learning deficits in DCD.

Correlation between bio-hydrogen production and polyhydroxybutyrate (PHB) synthesis by Rhodopseudomonas palustris WP3-5.

The aim of this study was to determine the competition between H(2) production and polyhydroxybutyrate (PHB) accumulation of Rhodopseudomonas palustris WP3-5 when grown on six different substrates. From the results, strain WP3-5 can utilize acetate, propionate, malate, and lactate to produce H(2) but can only synthesize PHB on acetate and propionate. The substrate conversion efficiency (SCE) on acetate and propionate increased significantly after the maximum PHB content was achieved, illustrating a competition for reducing power when PHB synthesis occurred. However, when strain WP3-5 was cultivated at suboptimal pH values on acetate, the synthesized PHB prevented strain WP3-5 from the stress of the inappropriate pH and retained H(2) producing efficiency as at optimal pH value. Consequently, although PHB synthesis does compete with H(2) production in R. palustris WP3-5, it is still conducive to H(2) production when strain WP3-5 is in a stressful condition.

The feasibility of biodiesel production by microalgae using industrial wastewater.

This study investigated nitrogen and phosphorus assimilation and lipid production of microalgae in industrial wastewater. Two native strains of freshwater microalgae were evaluated their biomass growth and lipid production in modified BBM medium. Chlamydomonas sp. TAI-2 had better biomass growth and higher lipid production than Desmodesmus sp.TAI-1. The optimal growth and lipid accumulation of Chlamydomonas sp. TAI-2 were tested under different nitrogen sources, nitrogen and CO(2) concentrations and illumination period in modified BBM medium. The optimal CO(2) aeration was 5% for Chlamydomonas sp. TAI-2 to achieve maximal lipid accumulation under continuous illumination. Using industrial wastewater as the medium, Chlamydomonas sp. TAI-2 could remove 100% NH(4)(+)-N (38.4 mg/L) and NO(3)(-)-N (3.1mg/L) and 33% PO(4)(3-)-P (44.7 mg/L) and accumulate the lipid up to 18.4%. Over 90% of total fatty acids were 14:0, 16:0, 16:1, 18:1, and 18:3 fatty acids, which could be utilized for biodiesel production.

Hydrogen production by Rhodopseudomonas palustris WP 3-5 in a serial photobioreactor fed with hydrogen fermentation effluent.

In this study, a lab-scale serial photobioreactor composed of three column reactors was constructed and continuously operated to investigate several parameters influencing photohydrogen production when using the synthetic wastewater and the anaerobic hydrogen fermentation effluents as the influents. The results indicated that better hydrogen production rate was obtained when the serial photobioreactor was operated under cellular recycling at a short HRT of 8h. The serial photobioreactor maintained high hydrogen content ca. 80% in the produced gas and 0.4× dilution ratio was the suitable ratio for hydrogen production. When the photobioreactor fed with the real wastewater (Effluent 1) containing 100 mg/L NH4Cl, Column 1 reactor successfully reduced ammonia concentration to about 60 mg/L for cell synthesis, resulting in a steady hydrogen production in the following two column reactors. The average hydrogen production rate was 205 mL-H2/L/d.

Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12).

Spinal cerebellar ataxia type 12 (SCA12) has been attributed to the elevated expression of ppp2r2b. To better elucidate the pathomechanism of the neuronal disorder and to search for a pharmacological treatment, Drosophila models of SCA12 were generated by overexpression of a human ppp2r2b and its Drosophila homolog tws. Ectopic expression of ppp2r2b or tws caused various pathological features, including neurodegeneration, apoptosis, and shortened life span. More detailed analysis revealed that elevated ppp2r2b and tws induced fission of mitochondria accompanied by increases in cytosolic reactive oxygen species (ROS), cytochrome c, and caspase 3 activity. Transmission electron microscopy revealed that fragmented mitochondria with disrupted cristae were engulfed by autophagosomes in photoreceptor neurons of flies overexpressing tws. Additionally, transgenic flies were more susceptible to oxidative injury induced by paraquat. By contrast, ectopic Drosophila Sod2 expression and antioxidant treatment reduced ROS and caspase 3 activity and extended the life span of the SCA12 fly model. In summary, our study demonstrates that oxidative stress induced by mitochondrial dysfunction plays a causal role in SCA12, and reduction of ROS is a potential therapeutic intervention for this neuropathy.

Utilization of the cyanobacteria Anabaena sp. CH1 in biological carbon dioxide mitigation processes.

Before switching totally to alternative fuel stage, CO(2) mitigation process has considered a transitional strategy for combustion of fossil fuels inevitably. In comparison to other CO(2) mitigation options, such as oceanic or geologic injection, the biological photosynthetic process would present a far superior and sustainable solution under both environmental and social considerations. The utilization of the cyanobacteria Anabaena sp. CH1 in carbon dioxide mitigation processes is analyzed in our research. It was found that an original developed photobioreactor with internal light source exhibits high light utilization. Anabaena sp. CH1 demonstrates excellent CO(2) tolerance even at 15% CO(2) level. This enables flue gas from power plant to be directly introduced to Anabaena sp. CH1 culture. Double light intensity and increased 47% CO(2) bubble retention time could enhance CO(2) removal efficiencies by 79% and 67%, respectively. A maximum CO(2) fixation rate of 1.01 g CO(2)L(-1)day(-1) was measured experimentally.

Correlation between fouling propensity of soluble extracellular polymeric substances and sludge metabolic activity altered by different starvation conditions.

Soluble extracellular polymeric substances (EPSs) cause membrane fouling in membrane bioreactors (MBRs), correlated with MBR sludge characteristics. Effects of F/M ratios on the evolution of soluble EPSs, fouling propensity of supernatants, and sludge metabolic activity were measured in this study in a two-period sequencing batch reactor (SBR). The experimental results show that fouling propensity was directly correlated with soluble-EPS concentration and composition. Sludge that had entirely lost active cells by long-term starvation released 64.4 ± 0.9 mg/L of humic acids, which caused a rapid increase in membrane resistance (40.67 ± 2.24 × 10(11) m(-1)) during fouling tests. During short-term starvation, induced by incubation at a normal to low F/M ratio of 0.05 d(-1), sludge can use previously secreted utilization-associated products (UAPs) to maintain endogenous respiration. Therefore, the strategies of accumulating sludge and prolonging sludge retention time in MBRs may create long-term starvation and promote membrane fouling.