[Show abstract][Hide abstract] ABSTRACT: Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45- FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)- fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45- FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45- FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1.
[Show abstract][Hide abstract] ABSTRACT: What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.
Proceedings of the National Academy of Sciences 09/2015; 112(41). DOI:10.1073/pnas.1512408112 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BDE209 and Pb are ubiquitous contaminants at e-waste recycling sites (EWRSs). This study aimed to determine acute and sub-acute toxicity to earthworm Eisenia fetida induced by BDE209 and Pb in natural soil. Results demonstrated that the inhibition of Pb on growth and reproduction of earthworms followed a dose-dependent pattern. Earthworms exposed to 100 mg kg(-1) of BDE209 displayed avoidance responses, while the soil indicated a more obvious decline of habitat function with the increase of Pb level. Comet assay suggested that increasing concentrations of Pb exposure resulted in a gradual increase in the tail length and olive tail moment, which meant that the degree of DNA damage was promoted. BDE209 addition could reduce the damage; therefore the joint effects of both chemicals showed antagonistic. These results revealed that joint exposure (BDE209-Pb) could elicit pronounced biochemical and physiological responses in earthworms, and the DNA damage might be potential molecular biomarker of the two pollutants.
[Show abstract][Hide abstract] ABSTRACT: There has been rising interest in the discovery of novel drug indications because of high costs in introducing new drugs. Many computational techniques have been proposed to detect potential drug-disease associations based on the creation of explicit profiles of drugs and diseases, while seldom research takes advantage of the immense accumulation of interaction data. In this work, we propose a matrix factorization model based on known drug-disease associations to predict novel drug indications. In addition, genomic space is also integrated into our framework. The introduction of genomic space, which includes drug-gene interactions, disease-gene interactions, and gene-gene interactions, is aimed at providing molecular biological information for prediction of drug-disease associations. The rationality lies in our belief that association between drug and disease has its evidence in the interactome network of genes. Experiments show that the integration of genomic space is indeed effective. Drugs, diseases, and genes are described with feature vectors of the same dimension, which are retrieved from the interaction data. Then a matrix factorization model is set up to quantify the association between drugs and diseases. Finally, we use the matrix factorization model to predict novel indications for drugs.
Computational and Mathematical Methods in Medicine 06/2015; 2015:1-9. DOI:10.1155/2015/275045 · 0.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-human primates offer unique opportunities to study the development of depression rooted in behavioral and physiological abnormalities. This study observed adult female rhesus macaques within social hierarchies and aimed to characterize the physiological and brain abnormalities accompanying depressive-like behavior. The behaviors of 31 female rhesus macaques from 14 different breeding groups were video recorded, and the footage was analyzed using the focal animal technique. There were 13 monkeys who never displayed huddling behavior (non-huddlers). The remaining 18 monkeys were divided into two groups according the mean time spent in the huddle posture. Four monkeys were designated as high huddlers, whereas the other 14 monkeys were low huddlers. An inverse relationship was discovered between social rank and depression. High huddlers spent more time engaging in physical contact and in close proximity to other monkeys, as well as less time spontaneously and reactively locomoting, than low huddlers and/or non-huddlers. Cortisol levels measured from the hair were elevated significantly in high huddlers compared with low huddlers and non-huddlers, and the measured cortisol levels were specifically higher in high huddlers than subordinate or dominant control monkeys. Regional cerebral blood flow data revealed significant and widespread decreases in high huddlers compared with non-huddlers.
[Show abstract][Hide abstract] ABSTRACT: The aerial filamentous microalga, Trentepohlia arborum (Chlorophyta), was cultured in three habitats - an aerial, a subaerial and an aquatic one - using different types of bioreactors. The growth, carotenoid productivity, and morphologic differences of T. arborum in different habitats were investigated. The maximum specific growth rate (μ) of the alga obtained in the logarithmic phase in the subaerial habitat was 0.034 h−1. HPLC analysis also demonstrated that T. arborum accumulated a high content of carotenoids. Zeaxanthin was the primary carotenoid in subaerial culture, while β,β-carotene was dominant in aerial culture. The maximum carotenoid productivity, 67.7 mg m−2 day−1, was reached when T. arborum was cultured in the subaerial habitat under nitrogen depletion using a novel attached cultivation bioreactor. Overall, it was demonstrated that T. arborum exhibited a relatively high growth rate and carotenoid productivity under attached cultivation.
[Show abstract][Hide abstract] ABSTRACT: Biofilm cultivation of microalgae has great potential in many applications. However, the water footprint for this method has not been well assessed. This issue was explored with the microalga Haematococcus pluvialis.
Only 1.25 l water is sufficient to support 1 m(2) biofilm cultivation surface. To produce 1 kg Haematococcus biomass and astaxanthin, the water footprint could be as low as 35.7 and 1440 l, respectively, by sealing the biofilm in a narrow chamber and supplying the proper amount of nutrients if the evaporation water loss was not considered. However, when loss of water by evaporation was considered, the water footprint was as low as 66.9 and 2700 l, respectively, if the chamber was aerated with CO2 at 0.014 vvm. These water footprint values are much lower than values obtained in other research work.
The water footprint of biofilm microalgal cultivation can be potentially reduced by more than 90 % if the biofilm is sealed in a narrow chamber and supplied with a slow aeration of CO2 as carbon source.
[Show abstract][Hide abstract] ABSTRACT: The ability of animals to respond to life-threatening stimuli is essential for survival. Although vision provides one of the major sensory inputs for detecting threats across animal species, the circuitry underlying defensive responses to visual stimuli remains poorly defined. Here, we investigate the circuitry underlying innate defensive behaviours elicited by predator-like visual stimuli in mice. Our results demonstrate that neurons in the superior colliculus (SC) are essential for a variety of acute and persistent defensive responses to overhead looming stimuli. Optogenetic mapping revealed that SC projections to the lateral posterior nucleus (LP) of the thalamus, a non-canonical polymodal sensory relay, are sufficient to mimic visually evoked fear responses. In vivo electrophysiology experiments identified a di-synaptic circuit from SC through LP to the lateral amygdale (Amg), and lesions of the Amg blocked the full range of visually evoked defensive responses. Our results reveal a novel collicular-thalamic-Amg circuit important for innate defensive responses to visual threats.
[Show abstract][Hide abstract] ABSTRACT: In Traditional Chinese Medicine theory, syndrome is essential to diagnose diseases and treat patients, and symptom is the foundation of syndrome differentiation. Thus the combination and interaction between symptoms represent the pattern of syndrome at phenotypic level, which can be modeled and analyzed using complex network. At first, we collected inquiry information of 364 depression patients from 2007 to 2009. Next, we learned classification models for 7 syndromes in depression using naïve Bayes, Bayes network, support vector machine (SVM), and C4.5. Among them, SVM achieves the highest accuracies larger than 0.9 except for Yin deficiency. Besides, Bayes network outperforms naïve Bayes for all 7 syndromes. Then key symptoms for each syndrome were selected using Fisher's score. Based on these key symptoms, symptom networks for 7 syndromes as well as a global network for depression were constructed through weighted mutual information. Finally, we employed permutation test to discover dynamic symptom interactions, in order to investigate the difference between syndromes from the perspective of symptom network. As a result, significant dynamic interactions were quite different for 7 syndromes. Therefore, symptom networks could facilitate our understanding of the pattern of syndrome and further the improvement of syndrome differentiation in depression.
Evidence-based Complementary and Alternative Medicine 03/2015; 2015:768249. DOI:10.1155/2015/768249 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: c-Met has emerged as an attractive target for targeted cancer therapy due to its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonyl-pyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of π-π stacking interactions and solvent accessible polar moieties led to a series of high potent and selective type I c-Met inhibitors. Based on in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development.
[Show abstract][Hide abstract] ABSTRACT: The signal transduction of acetylated histone can be processed through a recognition module-bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery, optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. SAR study on this new series led to several potent BRD4 inhibitors with IC50 about 0.05-0.1 μM in FP binding assay and GI50 0.1-0.3 μM in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anti-cancer drug development.
[Show abstract][Hide abstract] ABSTRACT: Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impacts on the oxidative perturbations and hydroxyl radical (·OH) generation in earthworms of exposure to the two chemicals remain almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the effects of Pb in earthworms Eisenia fetida in the presence of BDE209 through the use of several biomarkers in microcosms. The results have demonstrated that the addition of BDE209 (1 or 10 mg kg(-1)) decreased the enzymatic activities [superoxide dismutase, catalase (CAT), peroxidase] and total antioxidant capacity (T-AOC) compared with exposure to BDE209 alone (50, 250 or 500 mg kg(-1)). Electron paramagnetic resonance spectra indicated that ·OH radicals in earthworms were significantly induced by Pb in the presence of BDE209. The changing pattern of malondialdehyde (MDA) contents was accordant with that of ·OH intensity suggested that reactive oxygen species might lead to cellular lipid peroxidation. Furthermore, CAT exhibited more sensitive response to single Pb exposure than the other biomarkers, while T-AOC, ·OH and MDA might be three most sensitive biomarkers in earthworms after simultaneous exposure to Pb and BDE209. The results of these observations suggested that oxidative stress appeared in E. fetida, and it may play an important role in inducing the Pb and BDE209 toxicity to earthworms.
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence has shown that a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) moderates the association between stress and depressive symptoms. However, the exact etiologies underlying this moderation are not well understood. Here it is reported that among adult female rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) exerted an influence on cortisol responses to chronic stress. It was found that females with two copies of the short allele were associated with increased cortisol responses to chronic stress in comparison to their counterparts who have one or two copies of the long allele. In the absence of stress, no differences related to genotype were observed in these females. This genetic moderation was found without a genetic influence on exposure to stressful situations. Rather it was found to be a genetic modulation of cortisol responses to chronic stress. These findings indicate that the rh5-HTTLPR polymorphism is closely related to hypothalamus-pituitary-adrenal (HPA) axis reactivity, which may increase susceptibility to depression in females with low serotonin transporter efficiency and a history of stress.
Behavioural Brain Research 10/2014; 278. DOI:10.1016/j.bbr.2014.10.001 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Activated by NBS, readily available 1,2-trans-1-dihydroxyboryl benzyl S-glycosides served as glycosyl donors and reacted with certain simple alcohol acceptors to produce pure 1,2-cis-O-glycosides in moderate yields. The boronic acid moiety was revealed essential in the glycosylation for product formation and good anomeric ratio. The preliminary model reactions suggested that glycosyl aryl boronic acids could be used for stereoselective glycosylation.
Carbohydrate Research 10/2014; 398. DOI:10.1016/j.carres.2014.05.010 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Making full use of lipid and carbohydrate in microalgae for joint production of biodiesel and bioethanol may create a potential way to cut the high cost of single biofuel production from microalgae. Compared with conventional unicellular oleaginous microalgae, filamentous microalgae Tribonema sp. is richer in lipid and carbohydrate contents and lower protein content, thus, this study explores the suitability of Tribonema sp. as a substrate for joint production of biodiesel and bioethanol. Acid hydrolysis is the key step to saccharify wall cell into fermentable sugar and release lipid. Microalgae biomass (50g/L) was acid (3% H2SO4) hydrolyzed at 121°C for 45min to reach the maximum hydrolysis efficiency (81.48%). Subsequently, the lipid separated with hexane-ethanol from the hydrolysate was converted into microalgae biodiesel and the conversion rate was 98.47%. With yeast Saccharomyces cerevisiae, the maximum ethanol yield of 56.1% was reached from 14.5g/L glucose in hydrolysate.