Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the deposition of extracellular aggregates of amyloid-ß (Aß), the formation of intraneuronal tau neurofibrillary tangles and microglial activation-mediated neuroinflammation. One of the key molecules involved in microglial activation is galectin-3 (Gal-3). In recent years, extensive studies have dissected the mechanisms by which Gal-3 modulates microglial activation, impacting Aß deposition, in both animal models and human studies. In this review article, we focus on the emerging role of Gal-3 in biology and pathobiology, including its origin, its functions in regulating microglial activation and neuroinflammation, and its emergence as a biomarker in AD and other neurodegenerative diseases. These aspects are important to elucidate the involvement of Gal-3 in AD pathogenesis and may provide novel insights into the use of Gal-3 for AD diagnosis and therapy.

Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson's disease.

Purpose: This study is to investigate the relationship between thyroid function and Parkinson's disease (PD).Materials and Methods: Totally 77 PD patients were included, who were divided into tremor-dominant-type (TDT), akinetic-rigid-type (ART) and mixed-type (MXT) subgroups. Parkinsonism severity and stage was assessed by modified H-Y stage. Thyroid-stimulating hormone (TSH), fT3 and fT4 levels were detected to analyze thyroid function. Parameters of thyroid homeostasis, including thyroid's secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD) and Jostel's TSH index and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated and compared.Results: Thyroid hormone levels in PD patients were lower than normal controls. Patients with TDT/MXT had significantly higher fT4 level than those with ART. TSH levels were 1.73 ± 0.93 and 2.06 ± 1.04 ulU/ml for patients with TDT/MXT and ART, respectively. The patients in the TDT/MXT group had significantly lower SPINA-GD while significantly higher SPINA-GT than ART group. The fT3 level was significantly higher in early group than advanced group. TSH index in the early group was significantly higher than the advanced group. The fT4 level was negatively correlated with UPDRS motor score. Univariate and multivariable logistic regression analysis indicated that fT4 was positively correlated with PD motor subtype, which disappeared after adjusting for confounding factors. The fT3 level was negatively correlated with PD disease severity, even after adjusting for confounding factors. In female PD patients, fT4 level in TDT/MXT group was significantly higher than ART group. Male PD patients had higher fT4 levels in early patients than advanced patients. Percentage of patients exhibiting ART was decreased significantly in higher fT4 level subgroups. With the increase of TSH index and TTSI, the proportion of advanced PD patients gradually decreased. The proportion of PD patients with TDT/MXT motor subtype gradually increased with the quartiles of SPINA-GT.Conclusion: Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with PD.

Astragalus polysaccharide exerts anti-Parkinson via activating the PI3K/AKT/mTOR pathway to increase cellular autophagy level in vitro.

Astragalus polysaccharide (APS) is a bioactive macromolecule, which has been used to alleviate the development of Parkinson's disease (PD), while its mechanism is still unresolved. As is generally accepted that autophagy has an important link with PD, thus it is reasonable to hypothesize that APS was involved in autophagy pathway for the presence of anti-PD. To verify this hypothesis, PD model was induced by 100 µM 6-hydroxydopamine (6-HODA) in PC12 cells and then treated with different concentration of APS. Results showed that APS could increase cell viability and the level of autophagy, improve the formation of autophagosome, promote the conversion of LC3-I to LC3-II, showing APS could improve autophagy level. Moreover, APS could down-regulate the expression of pAKT and pmTOR, and up-regulate the expression of PTEN. While these proteins are involved in PI3K/AKT/mTOR pathway, we then knocked down (KD) endogenous PI3K protein (the PI3K/AKT/mTOR pathway receptor protein) in PC12 cells. Results showed that these events regulated by APS were reversed in PI3K KD cells, shown that APS activated autophagy through PI3K/AKT/mTOR pathway for treating PD. Altogether, APS has the role of increasing autophagy, and this event was responsible for inhibiting PI3K protein to activate PI3K/AKT/mTOR pathway.

Development of a tomographic Mueller-matrix scatterometer for nanostructure metrology.

In this paper, we describe the development of a novel instrument, tentatively called tomographic Mueller-matrix scatterometer (TMS), which enables illuminating sequentially a sample by a plane wave with varying illumination directions and recording, for each illumination, the polarized scattered field along various directions of observation in the form of scattering Mueller matrices. The incidence angle is varied from 0° to 65.6° with the rotation of a flat mirror that changes the position of the focal point of a light beam on the back focal plane of a high numerical aperture objective lens. The scattering Mueller matrices are collected over a wide range of scattering angles (0°-67°) and azimuthal angles (0°-360°). The developed instrument was then applied for the measurement of nanostructures in combination with an inverse scattering problem solving technique. The experiment performed on a periodic nanostructure preliminarily demonstrates the performance of TMS as well as its potential in nanostructure metrology. It is expected that the TMS would be a powerful tool for characterizing the polarized scattered-field distributions and measuring nanostructures in nanomanufacturing.

Reduced-basis boundary element method for fast electromagnetic field computation.

In this work, we combine conventional boundary element method (BEM) with the reduced-basis method (RBM) and propose a reduced-basis boundary element method (RB-BEM) to realize efficient modeling for parameterized electromagnetic scattering problems of dielectric scatterers. The RB-BEM allows for splitting the modeling process into a parameter-independent offline part and parameter-dependent online part, and replacing the high-dimensional original model obtained by conventional BEM with a low-dimensional reduced-basis model to improve computational efficiency of the online part. We also propose an improved greedy algorithm based on multi-grid to improve the computational efficiency of the offline part. The numerical experiments indicate that the efficiency of the improved greedy algorithm is several times higher than that of the standard one, and the solving efficiency of the reduced-basis model is several times to dozens of times higher than that of the original model with a prescribed approximation accuracy.

Adapting cultural mixture modeling for continuous measures of knowledge and memory fluency.

Previous research (e.g., cultural consensus theory (Romney, Weller, & Batchelder, American Anthropologist, 88, 313-338, 1986); cultural mixture modeling (Mueller & Veinott, 2008)) has used overt response patterns (i.e., responses to questionnaires and surveys) to identify whether a group shares a single coherent attitude or belief set. Yet many domains in social science have focused on implicit attitudes that are not apparent in overt responses but still may be detected via response time patterns. We propose a method for modeling response times as a mixture of Gaussians, adapting the strong-consensus model of cultural mixture modeling to model this implicit measure of knowledge strength. We report the results of two behavioral experiments and one simulation experiment that establish the usefulness of the approach, as well as some of the boundary conditions under which distinct groups of shared agreement might be recovered, even when the group identity is not known. The results reveal that the ability to recover and identify shared-belief groups depends on (1) the level of noise in the measurement, (2) the differential signals for strong versus weak attitudes, and (3) the similarity between group attitudes. Consequently, the method shows promise for identifying latent groups among a population whose overt attitudes do not differ, but whose implicit or covert attitudes or knowledge may differ.

Systematic tracking of dysregulated modules identifies disrupted pathways in narcolepsy.

OBJECTIVE: The objective of this work is to identify disrupted pathways in narcolepsy according to systematically tracking the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. Here, we performed systematic identification and comparison of modules across normal and narcolepsy conditions by integrating PPI and gene-expression data. METHODS: Firstly, normal and narcolepsy PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, modules in PPI network were explored by clique-merging algorithm and we identified altered modules using a maximum weight bipartite matching and in non-increasing order. Finally, pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test to illuminate the biological pathways in narcolepsy. RESULTS: Our analyses revealed that 235 altered modules were identified by comparing modules in normal and narcolepsy PPI network. Pathway functional enrichment analysis of disrupted module genes showed 59 disrupted pathways within threshold P < 0.001. The most significant five disrupted pathways were: oxidative phosphorylation, T cell receptor signaling pathway, cell cycle, Alzheimer's disease and focal adhesion. CONCLUSIONS: We successfully identified disrupted pathways and these pathways might be potential biological processes for treatment and etiology mechanism in narcolepsy.

Thyroid-stimulating hormone levels within the reference range are associated with serum lipid profiles independent of thyroid hormones.

CONTEXT AND OBJECTIVE: Dyslipidemia in thyroid dysfunction has always been attributed to changes in thyroid hormone (TH) levels. We hypothesized that TSH plays an important role in lipid metabolism independent of TH. DESIGN AND SETTING: We conducted a cross-sectional study to investigate the relationship between serum TSH levels and lipid profiles after controlling for free T(3), free T(4), total T(3), total T(4) and nonthyroid factors relevant to lipid metabolism in euthyroid Chinese subjects. MAIN OUTCOME MEASURES: General linear analysis was performed to determine whether the impact of TSH on serum lipid levels is independent of the TH levels. Moreover, path analysis, an evolutionary multivariable regression technique, was conducted to test whether there is a direct and/or indirect effect between serum TSH and total cholesterol (TC) levels. Additionally, the odds ratios (95% confidence interval) for hypercholesterolemia in relation to TSH categories were calculated. RESULTS: A total of 3664 euthyroid subjects were finally analyzed. There was a significant linear trend toward higher log TC (P = 0.021) and log triglyceride (P = 0.001) levels with increasing serum TSH levels within the reference range, which remained significant after adjusting for factors such as TH levels, age, and smoking. Most importantly, the total effect of TSH on TC levels (total effect(TC, TSH) = 0.05253) includes a direct effect (direct effect(TC, TSH) = 0.05979) and an indirect effect via TH. Compared with subjects in the lower part of the reference range (TSH level, 0.27-0.61 mIU/liter), the adjusted odds ratio for hypercholesterolemia was 3.239 (95% confidence interval, 1.392-7.538; P = 0.007) for those in the upper category (TSH level, 4.61-5.5 mIU/liter). CONCLUSIONS: The variation in normal TSH levels is partially related to the lipid components and hypercholesterolemia in euthyroid subjects and includes both TH-dependent and TH-independent effects. Our study suggests the importance of controlling TSH in hypothyroid subjects.