Loss of Flot2 expression in deep cerebellar nuclei neurons of mice with Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is caused by a deficiency of the NPC1 or NPC2 gene, leading to storages of unesterified cholesterol and sphingolipids. Cerebellar ataxia is a main symptom of NPC and the deep cerebellar nuclei (DCN) is the sole signal output of the cerebellum. In this study, we explored the pathological changes in DCN neurons of Npc1 knockout mice (Npc1-). We first demonstrated that DCN neurons of Npc1- mice had prominent ganglioside GM2 accumulation in the late endosomes but not in the lysosomes. More importantly, Flot2 expression, a marker for the lipid rafts, was lost. Single-nucleus RNA sequencing analysis revealed a generalized reduction in gene expression in DCN neurons, though Camk1d, encoding one of the Ca2+/calmodulin-dependent protein kinases (CaMKs), increased in expression. We treated Npc1- mice with CaMK inhibitor KN-93, but CaMK1D expression increased further. We also fed Npc1- mice with two medications for NPC. We found that miglustat, a sphingolipid synthesis inhibitor, increased the expression of Flot2. Moreover, N-acetyl l-leucine (NALL), an experimental medicine for NPC, recovered Flot2 expression. Therefore, our data suggest that in Npc1- mice, GM2 sequestration and the loss of lipid rafts lead to cell dysfunction and symptoms of NPC.

Comammox Nitrospira Clade B is the most abundant complete ammonia oxidizer in a dairy pasture soil and inhibited by dicyandiamide and high ammonium concentrations.

The recent discovery of comammox Nitrospira, a complete ammonia oxidizer, capable of completing the nitrification on their own has presented tremendous challenges to our understanding of the nitrification process. There are two divergent clades of comammox Nitrospira, Clade A and B. However, their population abundance, community structure and role in ammonia and nitrite oxidation are poorly understood. We conducted a 94-day microcosm study using a grazed dairy pasture soil amended with urea fertilizers, synthetic cow urine, and the nitrification inhibitor, dicyandiamide (DCD), to investigate the growth and community structure of comammox Nitrospira spp. We discovered that comammox Nitrospira Clade B was two orders of magnitude more abundant than Clade A in this fertile dairy pasture soil and the most abundant subcluster was a distinctive phylogenetic uncultured subcluster Clade B2. We found that comammox Nitrospira Clade B might not play a major role in nitrite oxidation compared to the role of canonical Nitrospira nitrite-oxidizers, however, comammox Nitrospira Clade B is active in nitrification and the growth of comammox Nitrospira Clade B was inhibited by a high ammonium concentration (700 kg synthetic urine-N ha-1) and the nitrification inhibitor DCD. We concluded that comammox Nitrospira Clade B: (1) was the most abundant comammox in the dairy pasture soil; (2) had a low tolerance to ammonium and can be inhibited by DCD; and (3) was not the dominant nitrite-oxidizer in the soil. This is the first study discovering a new subcluster of comammox Nitrospira Clade B2 from an agricultural soil.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Self-assembly and Hydrogelation Properties of Peptides Derived from Peptic Cleavage of Aggregation-prone Regions of Ovalbumin.

Egg white protein hydrolysate generated with pepsin was investigated for the presence of peptides with self-assembly and hydrogelation properties. Incubation of the hydrolysates for 16 h resulted in aggregates with significantly (p < 0.05) lower free amino nitrogen and sulfhydryl contents, and higher particle diameter and surface hydrophobicity compared to the hydrolysates. LC-MS/MS analysis of the aggregates resulted in identification of 429 ovalbumin-derived peptides, among which the top-six aggregation-prone peptides IFYCPIAIM, NIFYCPIAIM, VLVNAIVFKGL, YCPIAIMSA, MMYQIGLF, and VYSFSLASRL were predicted using AGGRESCAN by analysis of the aggregation "Hot Spots". NIFYCPIAIM had the highest thioflavin T fluorescence intensity, particle diameter (5611.3 nm), and polydispersity index (1.0) after 24 h, suggesting the formation of ß-sheet structures with heterogeneous particle size distribution. Transmission electron microscopy of MMYQIGLF, and VYSFSLASRL demonstrated the most favorable peptide self-assembly, based on the formation of densely packed, intertwined fibrils. Rheological studies confirmed the viscoelastic and mechanical properties of the hydrogels, with IFYCPIAIM, NIFYCPIAIM, VLVNAIVFKGL, and VYSFSLASRL forming elastic solid hydrogels (tan δ < 1), while YCPIAIMSA and MMYQIGLF formed viscous liquid-like hydrogels (tan δ > 1). The results provide valuable insight into the influence of peptide sequence on hydrogelation and self-assembly progression, and prospects of food peptides in biomaterial applications.

Normative Data of Mini-Mental State Examination, Montreal Cognitive Assessment, and Alzheimer's Disease Assessment Scale-Cognitive Subscale of Community-Dwelling Older Adults in Taiwan.

INTRODUCTION: Appropriate tools and references are essential for evaluating individuals' cognitive levels. This study validated the Taiwan version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) and provided normative data for the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and ADAS-cog in community-dwelling older adults. METHODS: MMSE, MoCA, and ADAS-cog were administered to 150 nondemented healthy adults aged 55-85 years during 2018-2020 as part of the Northeastern Taiwan Community Medicine Research Cohort. ADAS-cog was translated from the original English version to traditional Chinese with cultural and language considerations in Taiwan. Cronbach's alpha (α) tested the reliability of ADAS-cog, and Pearson correlations examined its external validity using MMSE and MoCA as comparisons. Normative data were generated and stratified by age and education, and the one-way analysis of variance compared scores between age and education groups. Another 20 hospital-acquired participants with cognitive impairment joined the 150 healthy participants. Comparisons in the Clinical Dementia Rating (CDR) tiers tested the discriminability of the tests for different cognitive levels. The area under the receiver operating characteristic curve (AUROC) analyzed the power of ADAS-cog in predicting CDR 0.5 from CDR 0. RESULTS: The Taiwan version of ADAS-cog had fair reliability between items (α = 0.727) and good correlations to MMSE (r = -0.673, p < 0.001) and MoCA (r = -0.746, p < 0.001). The normative data of MMSE, MoCA, and ADAS-cog showed ladder changes with age (p = 0.006, 0.001, and 0.437) and education (p < 0.001, <0.001, and <0.001) in the 150 nondemented older adults. Next, in the 170 mixed participants from the communities and the hospital, MMSE, MoCA, and ADAS-cog scores were well differentiable between CDR 0, 0.5, and 1. In addition, ADAS-cog discriminated CDR 0.5 from 0 by an AUROC of 0.827 (p < 0.001). DISCUSSION/CONCLUSION: The three structured cognitive tests consistently reflect cognitive levels of healthy older adults. The Taiwan version of ADAS-cog is compatible with MMSE and MoCA to distinguish people with mildly impaired from normal cognition. In addition, this study derived MMSE, MoCA, and ADAS-cog norms tailored to demographic factors. The findings highlight the need for stratification of age and education rather than applying a fixed cutoff for defining normal and abnormal cognition.

The effect of China's open-door tourism policy on Taiwan: Promoting or suppressing tourism from other countries to Taiwan?

This study employs an extended gravity model to analyse the complementarity or competitiveness relationship of the number of inbound tourists and corresponding tourism revenue between China and 19 other nations under the implementation of China's Open-door Tourism Policy to Taiwan in 2008. A simulation for 2018-2021 demonstrates the sustained impact of this policy. The results show that the number of tourists to Taiwan from China reached its peak in 2015 at 41% and will decrease to 9% by 2021. The corresponding tourism revenue will decrease from 49% to 11% over the same period. The results also show that if the number of tourists from China remains above 836,772, the number of tourists from Japan, Hong Kong, Australasia, North America, and Europe will still increase. However, the number of tourists from South Korea and South and Southeast Asia will increase continuously regardless of tourists from China, even far below 836,772.

Genetic associations and expression of extra-short isoforms of disrupted-in-schizophrenia 1 in a neurocognitive subgroup of schizophrenia.

Disrupted-in-schizophrenia 1 (DISC1) was reported to be associated with schizophrenia. In a previous study, we found significant association with schizophrenia patients with deficient sustained attention assessed by continuous performance test (CPT). This study aimed to identify risk polymorphisms in this specific neurocognitive subgroup and investigate the expression of different isoforms of DISC1. A total of 83 genetic variants were identified through direct sequencing in 50 controls and 100 schizophrenia patients. Fourteen variants were genotyped in 600 controls and 912 patients. Patients were subgrouped by familial loading (multiplex or simplex) and performance on CPT. The frequency of AA genotype of rs11122324 at the 3'-UTR of Es and Esv1 isoforms and of rs2793091 at intron 4 were significantly higher in multiplex schizophrenia patients than those in controls (corrected p < 0.05). In further subgrouping, the frequency of AA genotype of the two SNPs were significantly higher in multiplex schizophrenia patients with deficient sustained attention than those in controls (corrected p < 0.005). The mRNA expression levels of two extra-short isoforms (Es and Esv1) in the EBV-transformed lymphocytes of schizophrenia were significantly higher than those of controls. Luciferase reporter assays demonstrated that the A-allele of rs11122324 significantly upregulated DISC1 extra-short isoforms transcription compared with the G-allele. We found two SNPs (rs11122324 and rs2793091) of DISC1 may be specifically associated with multiplex schizophrenia patients with deficient sustained attention. The SNP rs11122324 may be a risk polymorphism, which may have functional influence on the transcription of Es and Esv1 through increasing their expression.

An electroneurography-based assay for identifying injured nerve segment during surgery: design and in vivo application in the rat.

OBJECTIVE: Nerve injury is the main reason for nerve reconstruction surgery, during which the surgeon must determine the location of the injured nerve segment, resect it, and reconnect the remaining healthy nerve stump ends within a limited time. Given this importance, an assay needed to determine the exact location of the injured nerve segment, but no tool has yet fulfilled this need so that a visual inspection of the nerve is still the primary method of identifying the injured segment. APPROACH: We designed a flexible multi-electrode array sensor that records the electroneurographic signal (ENG) as the action potential elicited by electrical stimulation that propagates along the nerve upon both orthodromic and antidromic stimulation. Its utility was validated by in vivo experiments in injured sciatic nerves of rats. MAIN RESULTS: The results showed that the first post stimulus negative electroneurographic component (N1) is the most valid neural correlate, as its amplitude decreased, and latency increased as the action potential propagated across the injured segment. Gradual recovery of nerve conduction was observed when measured immediately, 7, and 30 d after injury. The locations of the identified injured segments were validated by histological findings. SIGNIFICANCE: The sensor and the algorithm developed in this study are breakthroughs in surgical nerve assessment accomplished by determining the specific nerve segment that should be resected, enabling the optimal surgical outcome.

On revealing the gene targets of Ebola virus microRNAs involved in the human skin microbiome.

Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and has a high mortality rate. Histopathological and immunopathological analyses of Ebola virus have revealed that histopathological changes in skin tissue are associated with various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial for the skin immune shield. The discovery of microRNAs (miRNAs) in Ebola virus implies that immune escape, endothelial cell rupture, and tissue dissolution during Ebola virus infection are a result of the effects of Ebola virus miRNAs. Keratinocytes obtained from normal skin can attach and spread through expression of the thrombospondin family of proteins, playing a role in initiation of cell-mediated immune responses in the skin. Several miRNAs have been shown to bind the 3' untranslated region of thrombospondin mRNA, thereby controlling its stability and translational activity. In this study, we discovered short RNA sequences that may act as miRNAs from Propionibacterium acnes using a practical workflow of bioinformatics methods. Subsequently, we deciphered the common target gene. These RNA sequences tended to bind to the same thrombospondin protein, THSD4, emphasizing the potential importance of the synergistic binding of miRNAs from Ebola virus, Propionibacterium acnes, and humans to the target. These results provide important insights into the molecular mechanisms of thrombospondin proteins and miRNAs in Ebola virus infection.

Influence of copper on expression of nirS, norB and nosZ and the transcription and activity of NIR, NOR and N2 OR in the denitrifying soil bacteria Pseudomonas stutzeri.

Reduction of the potent greenhouse gas nitrous oxide (N(2)O) occurs in soil environments by the action of denitrifying bacteria possessing nitrous oxide reductase (N(2)OR), a dimeric copper (Cu)-dependent enzyme producing environmentally benign dinitrogen (N(2)). We examined the effects of increasing Cu concentrations on the transcription and activity of nitrite reductase (NIR), nitric oxide reductase (NOR) and N2 OR in Pseudomonas stutzeri grown anaerobically in solution over a 10-day period. Gas samples were taken on a daily basis and after 6 days, bacterial RNA was recovered to determine the expression of nirS, norB and nosZ encoding NIR, NOR and N(2)OR respectively. Results revealed that 0.05 mM Cu caused maximum conversion of N(2)O to N(2) via bacterial reduction of N(2)O. As soluble Cu generally makes up less than 0.001% of total soil Cu, extrapolation of 0.05 mg l(-l) soluble Cu would require soils to have a total concentration of Cu in the range of, 150-200 µg g(-1) to maximize the proportion of N(2)O reduced to N(2). Given that many intensively farmed agricultural soils are deficient in Cu in terms of plant nutrition, providing a sufficient concentration of biologically accessible Cu could provide a potentially useful microbial-based strategy of reducing agricultural N(2)O emissions.

Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits.

D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia.

The role of gluconate production by Pseudomonas spp. in the mineralization and bioavailability of calcium-phytate to Nicotiana tabacum.

Organic phosphorus (P) is abundant in most soils but is largely unavailable to plants. Pseudomonas spp. can improve the availability of P to plants through the production of phytases and organic anions. Gluconate is a major component of Pseudomonas organic anion production and may therefore play an important role in the mineralization of insoluble organic P forms such as calcium-phytate (CaIHP). Organic anion and phytase production was characterized in 2 Pseudomonas spp. soil isolates (CCAR59, Ha200) and an isogenic mutant of strain Ha200, which lacked a functional glucose dehydrogenase (Gcd) gene (strain Ha200 gcd::Tn5B8). Wild-type and mutant strains of Pseudomonas spp. were evaluated for their ability to solubilize and hydrolyze CaIHP and to promote the growth and assimilation of P by tobacco plants. Gluconate, 2-keto-gluconate, pyruvate, ascorbate, acetate, and formate were detected in Pseudomonas spp. supernatants. Wild-type pseudomonads containing a functional gcd could produce gluconate and mineralize CaIHP, whereas the isogenic mutant could not. Inoculation with Pseudomonas improved the bioavailability of CaIHP to tobacco plants, but there was no difference in plant growth response due to Gcd function. Gcd function is required for the mineralization of CaIHP in vitro; however, further studies will be needed to quantify the relative contribution of specific organic anions such as gluconate to plant growth promotion by soil pseudomonads.

HemX is required for production of 2-ketogluconate, the predominant organic anion required for inorganic phosphate solubilization by Burkholderia sp. Ha185.

The bacterium Burkholderia sp. Ha185 readily solubilizes inorganic phosphate by releasing the low molecular weight organic anion, 2-ketogluconate. Using random transposon mutagenesis and in silico analysis, a mutation that caused almost complete abolition of phosphate solubilization was located within hemX, which is part of the hem operon. Burkholderia sp. Ha185 HemX is a multidomain protein, predicted to encode a bifunctional uroporphyrinogen-III synthetase/uroporphyrin-III C-methyltransferase, which has not previously been implicated in phosphate solubilization. Complementation of hemX restored the ability of the mutant to solubilize phosphate in both plate and liquid cultures. Based on a combination of organic-anion profiling, quantitative polymerase chain reaction and in silico analyses, hemX was confirmed to be solely responsible for hydroxyapatite solubilization in Burkholderia sp. Ha185. It is proposed that the biosynthesis of a yet to be determined redox cofactor by HemX is the main pathway for generating 2-ketogluconate via a haem-dependent gluconate 2-dehydrogenase in Burkholderia sp. Ha185.

Association Between History of Severe Hypoglycemia and Risk of Falls in Younger and Older Patients With Diabetes.

To compare the incidence and relative risk of falls between adults with and without diabetes, and to prospectively assess the role of history of severe hypoglycemia in the putative relationship between diabetes and falls in younger and older people, respectively.The National Health Insurance Research Database in Taiwan was used in this cohort study. Diabetic cases (with and without history of severe hypoglycemia) and nondiabetic people were followed from 2000 to 2009. There were 31,049 people enrolled in each of the 3 groups. Subdistribution hazard ratio (sHR) of falls was estimated with considering death as a competing risk by using Fine and Gray method. Demographic characteristics, diabetes-related complications, and comorbidities associated with falls were adjusted in multivariable Cox regression model.As compared to nondiabetic people, adjusted sHR was 1.13 for diabetes without history of severe hypoglycemia (DwoH) and 1.63 for diabetes with history of severe hypoglycemia (DwH), respectively. DwH group was associated with a higher risk than DwoH (adjusted sHR = 1.57). All of the excessive risks were more pronounced in people younger than 65 years old than in older people.Patients with diabetes had increased risk of falls. Severe hypoglycemia was further associated with a higher risk in diabetes, the increased hazards were particularly pronounced in people younger than 65 years old. Because falls in younger people may result in a greater economic and social loss, our study call for proper attentions to prevention of falls in younger patients (<65 years old) with diabetes.

A Population-Based Cohort Study of All-Cause and Site-Specific Cancer Incidence Among Patients With Type 1 Diabetes Mellitus in Taiwan.

BACKGROUND: The relationship between type 1 diabetes mellitus (T1DM) and cancer incidence remains unclear. We sought to assess the all-cause and site-specific cancer incidence in patients with T1DM. METHODS: A retrospective cohort study design was employed, in which 14 619 patients with T1DM were retrieved from Taiwan's National Health Insurance medical claims between 2000 and 2007. The study subjects were followed to the end of 2008, and cancer incidence was assessed. We calculated age-, sex-, and calendar year-standardized incidence ratios (SIRs) of all-cause cancer incidence and site-specific neoplasm incidence, with reference to the general population. RESULTS: Seven hundred and sixty patients were identified for all-cause cancer over 86,610 person-years, representing an incidence rate of 87.75 cases per 10,000 person-years. The incidence rate was higher in males than in female patients (109.86 vs 69.75 cases per 10,000 person-years). T1DM was associated with a significantly increased SIR of all-cause cancer (1.13; 95% confidence interval [CI], 1.05-1.22). The sex-specific SIR was significantly elevated in female patients (1.19; 95% CI, 1.07-1.33), but the SIR for male patients was insignificantly elevated (1.09; 95% CI, 0.99-1.20). Pancreatic cancer showed the greatest increase in SIR among both male and female patients with T1DM. Male patients experienced significantly increased SIRs for kidney, rectum, liver, and colon neoplasm, and significantly increased SIRs were noted for ovarian, bladder, and colon cancer in female patients. CONCLUSIONS: T1DM was associated with a 13% increase in risk of all-cause cancer incidence. Patients with T1DM should be advised to undergo cancer screening for certain types of cancer.

Temperature-Dependent Galleria mellonella Mortality as a Result of Yersinia entomophaga Infection.

The bacterium Yersinia entomophaga is pathogenic to a range of insect species, with death typically occurring within 2 to 5 days of ingestion. Per os challenge of larvae of the greater wax moth (Galleria mellonella) confirmed that Y. entomophaga was virulent when fed to larvae held at 25°C but was avirulent when fed to larvae maintained at 37°C. At 25°C, a dose of ~4 × 10(7) CFU per larva of a Y. entomophaga toxin complex (Yen-TC) deletion derivative, the Y. entomophaga ΔTC variant, resulted in 27% mortality. This low level of activity was restored to near-wild-type levels by augmentation of the diet with a sublethal dose of purified Yen-TC. Intrahemocoelic injection of ~3 Y. entomophaga or Y. entomophaga ΔTC cells per larva gave a 4-day median lethal dose, with similar levels of mortality observed at both 25 and 37°C. Following intrahemocoelic injection of a Yen-TC YenA1 green fluorescent protein fusion strain into larvae maintained at 25°C, the bacteria did not fluoresce until the population density reached 2 × 10(7) CFU ml(-1) of hemolymph. The observed cells also took an irregular form. When the larvae were maintained at 37°C, the cells were small and the observed fluorescence was sporadic and weak, being more consistent at a population density of ~3 × 10(9) CFU ml(-1) of hemolymph. These findings provide further understanding of the pathobiology of Y. entomophaga in insects, showing that the bacterium gains direct access to the hemocoelic cavity, from where it rapidly multiplies to cause disease.

Nonperturbative mean-field theory for minimum enstrophy relaxation.

The dual cascade of enstrophy and energy in quasi-two-dimensional turbulence strongly suggests that a viscous but otherwise potential vorticity (PV) conserving system decays selectively toward a state of minimum potential enstrophy. We derive a nonperturbative mean field theory for the dynamics of minimum enstrophy relaxation by constructing an expression for PV flux during the relaxation process. The theory is used to elucidate the structure of anisotropic flows emerging from the selective decay process. This structural analysis of PV flux is based on the requirements that the mean flux of PV dissipates total potential enstrophy but conserves total fluid kinetic energy. Our results show that the structure of PV flux has the form of a sum of a positive definite hyperviscous and a negative or positive viscous transport of PV. Transport parameters depend on zonal flow and turbulence intensity. Turbulence spreading is shown to be related to PV mixing via the link of turbulence energy flux to PV flux. In the relaxed state, the ratio of the PV gradient to zonal flow velocity is homogenized. This homogenized quantity sets a constraint on the amplitudes of PV and zonal flow in the relaxed state. A characteristic scale is defined by the homogenized quantity and is related to a variant of the Rhines scale. This relaxation model predicts a relaxed state with a structure which is consistent with PV staircases, namely, the proportionality between mean PV gradient and zonal flow strength.

Protective effects of Houttuynia cordata aqueous extract in mice consuming a high saturated fat diet.

The protective effects of Houttuynia cordata aqueous extract (HCAE) in mice consuming a high saturated fat diet (HFD) were examined. HCAE, at 0.5, 1, or 2%, was supplied in drinking water for 8 weeks. HCAE was rich in phenolic acids and flavonoids. HCAE intake at 1 and 2% decreased body weight, epididymal fat, insulin resistance, triglyceride and total cholesterol contents in plasma and liver from HFD-treated mice (p < 0.05). HFD enhanced hepatic activity of malic enzyme, fatty acid synthase (FAS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase; and augmented the hepatic level of saturated fatty acids (p < 0.05). HCAE intake at 2% reduced malic enzyme and FAS activities, and lowered saturated fatty acids content in liver (p < 0.05). HCAE suppressed HFD induced oxidative and inflammatory stress in the heart and liver via reducing the malondialdehyde level, retaining glutathione content and glutathione peroxidase activity, decreasing tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 production (p < 0.05). These results support that Houttuynia cordata is a potent food against HFD induced obesity, and oxidative and inflammatory injury.

Quantum dot nanoparticles affect the reproductive system of Caenorhabditis elegans.

Quantum dots (QDs) are an increasingly important class of nanoparticle, but little ecotoxicological data for QDs has been published to date. The effects of mercaptosuccinic acid (MSA)-capped QDs (QDs-MSA) and equivalent concentrations of cadmium (Cd) from cadmium chloride on growth and reproduction of the nematode Caenorhabditis elegans (Rhabditidae) were assessed in laboratory experiments. Growth from larvae to adults of C. elegans was unaffected by exposure to 1 µM fluorescent QDs-MSA, but adults produced more embryos and laid them prematurely. Furthermore, C. elegans exposed to QDs-MSA (1 µM) showed a high percentage of embryo mortality (19.2 ± 0.5, p < 0.001, percentage ± standard deviation) compared with unexposed nematodes (11.6 ± 0.4). An egg-laying defect phenotype was also observed at high frequency in response to 1 µM QDs-MSA exposure (38.3 ± 3.6%, p < 0.01; control 10.0 ± 2.2%). This resulted in a reduced mean life span (20.5 ± 1.1 d, p < 0.05) compared with the control (24.6 ± 1.0 d). Cadmium also caused reduced life span in C. elegans, but a low incidence of egg-laying defects was observed, suggesting that Cd and QDs-MSA affected C. elegans by different mechanisms. Furthermore, egg-laying defects caused by QDs-MSA responded to the addition of the anticonvulsant ethosuximide and to a lesser extent to the neurotransmitter serotonin, suggesting that QDs-MSA might have disrupted motor neurons during the reproduction process.

The novel indole compound SK228 induces apoptosis and FAK/Paxillin disruption in tumor cell lines and inhibits growth of tumor graft in the nude mouse.

Drugs in clinical use with indole structure exhibit side effects. Therefore, to search for indole compounds with more efficacy and less side effect for cancer therapy, we developed a novel indole compound SK228 and examined its effects and mechanisms on antitumor growth and invasion inhibition in cell and tumor xenografts in nude mice models. SK228 significantly inhibited growth of different lung and esophageal cancer cell lines at sub-micromolar range, but not normal lung cells. SK228 induced DNA damages mainly by producing reactive oxygen species (ROS) resulting in apoptosis. SK228 treatment increased the release of cytochrome c into the cytosol along with the increased activity of caspase-3 and -9 without affecting caspase-8, whereas these effects were attenuated by ROS inhibitor. The expression levels of BCL-2 family regulators were also affected. Moreover, low-dose SK228 significantly reduced the invasion of cancer cells. The active phosphorylated form of FAK/Paxillin signaling pathway proteins and active form of RhoA were decreased. Moreover, the F-actin cytoskeleton was disrupted after low-dose SK228 treatment. Growth of an A549 tumor cell xenograft was markedly inhibited without significant side effects. SK228-induced apoptosis was confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry of cleaved caspase-3 in tumors from treated mice. Our study provides the first evidence that SK228 exhibits cancer cell-specific cytotoxicity by inducing mitochondria-mediated apoptosis. In addition, SK228 inhibits cancer cell invasion via FAK/Paxillin disruption at noncytotoxic doses. SK228 can be further tested as a pharmaceutical compound for cancer treatment.