Mind Wandering in Sensory Cortices

Mind wandering contains rich phenomenology as we experience moment by moment, however, such linkage between our subjective experiences and the underlying neural mechanism has been missing in the literature. Here we report that the sensory contents of mind wandering recruit corresponding sensory cortices, serving as the neural bases of the sensory contents in mind wandering

STRUCTURAL CHARACTERIZATION OF OLIGOSACCHARIDES AND UNDERSTANDING HEPARAN SULFATE-PROTEIN INTERACTIONS

Heparin is known as a widely used anticoagulant drug since the 1930s. Heparin and heparan sulfate (HS) are highly sulfated polysaccharides that consist of a repeating disaccharide unit of glucosamine and glucuronic (GlcA) or iduronic acid (IdoA). The polydispersity of the saccharide sequence as well as the polyheterogeneity of the sulfation pattern make the study of this type of carbohydrate a formidable task. Instead of traditional extraction from animal mucus, we use the chemoenzymatic approach to synthesize homogeneous heparin oligosaccharides. The synthetic low molecular weight heparin was proven anti-FXa activity with reversible anticoagulant activity. In addition to secure the supply chain, the extra benefits aid future clinical usage of synthetic heparin drug. On the other side, the availability of synthetic pure common and less abundant HS oligosaccharides can serve as heparin component standards to secure the drug safety. Take the advantage of chemoenzymatic synthesis, the sufficient amount of structurally tailored oligosaccharide reagents are accessible. To investigate the interaction between HS and proteins, several oligosaccharide probes were successfully developed. Firstly, a synthesized heptasaccharide was used to co-crystalize with 2-O-sulfotransferase (2-OST) and probe the molecular basis of specificity. 2-OST was found to recognize N-sulfo and exclude 6-O-sulfo group of substrates, supporting the biosynthetic hypothesis 2-O-sulfation occurs after N-sulfation and prior to 6-O-sulfation. Secondly, we designed and synthesized the active heparan sulfate oligosaccharide probe carrying a diazoacetyl group. The resultant oligosaccharides demonstrate inhibitory activity and structural selectivity toward HS biosynthetic enzyme 2-OST and 3-OST, respectively. Thirdly, 13C-labeled saccharide was introduced at the desired site of the oligosaccharide to enhance the intensity of NMR signals. The labeled reagents facilitate directly analysis the binding between specific saccharide and protein. Finally, nuclear magnetic resonance analyses were performed to obtain coupling constants and full chemical shift assignments of all synthetic oligosaccharides. Comparing to relatively rigid GlcA, IdoA shows structural plasticity and diverse conformational preference in response to different sulfation patterns, which may be critical for various protein specific binding. The success of these projects assists the fundamental understand of HS-protein interaction as well as the design of next generation heparin-based therapeutics.Doctor of Philosoph

Is deck B a disadvantageous deck in the Iowa Gambling Task?

BACKGROUND: The Iowa gambling task is a popular test for examining monetary decision behavior under uncertainty. According to Dunn et al. review article, the difficult-to-explain phenomenon of "prominent deck B" was revealed, namely that normal decision makers prefer bad final-outcome deck B to good final-outcome decks C or D. This phenomenon was demonstrated especially clearly by Wilder et al. and Toplak et al. The "prominent deck B" phenomenon is inconsistent with the basic assumption in the IGT; however, most IGT-related studies utilized the "summation" of bad decks A and B when presenting their data, thereby avoiding the problems associated with deck B. METHODS: To verify the "prominent deck B" phenomenon, this study launched a two-stage simple version IGT, namely, an AACC and BBDD version, which possesses a balanced gain-loss structure between advantageous and disadvantageous decks and facilitates monitoring of participant preferences after the first 100 trials. RESULTS: The experimental results suggested that the "prominent deck B" phenomenon exists in the IGT. Moreover, participants cannot suppress their preference for deck B under the uncertain condition, even during the second stage of the game. Although this result is incongruent with the basic assumption in IGT, an increasing number of studies are finding similar results. The results of the AACC and BBDD versions can be congruent with the decision literatures in terms of gain-loss frequency. CONCLUSION: Based on the experimental findings, participants can apply the "gain-stay, loss-shift" strategy to overcome situations involving uncertainty. This investigation found that the largest loss in the IGT did not inspire decision makers to avoid choosing bad deck B

Design and synthesis of active heparan sulfate-based probes

A chemoenzymatic approach for synthesizing heparan sulfate oligosaccharides with a reactive diazoacetyl saccharide residue is reported. The resultant oligosaccharides were demonstrated to serve as specific inhibitors for heparan sulfate sulfotransferases, offering a new set of tools to probe the structural selectivity for heparan sulfate-binding proteins

Uncovering the Relationship between Sulphation Patterns and Conformation of Iduronic Acid in Heparan Sulphate

The L-iduronic acid (IdoA) residue is a critically important structural component in heparan sulphate polysaccharide for the biological functions. The pyranose ring of IdoA is present in 1C4-chair, 2SO-skew boat, and less frequently, in 4C1-chair conformations. Here, we analyzed the conformation of IdoA residue in eight hexasaccharides by NMR. The data demonstrate a correlation between the conformation of IdoA and sulphations in the surrounding saccharide residues. For the 2-O-sulpho IdoA residue, a high degree of sulphation on neighboring residues drives ring dynamics towards the 2SO-skew boat conformer. In contrast, the nonsulphated IdoA residue is pushed towards the 1C4-chair conformer when the neighboring residues are highly sulphated. Our data suggest that the conformation of IdoA is regulated by the sulphation pattern of nearby saccharides that is genetically controlled by the heparan sulphate biosynthetic pathway

Evaluation on the Pharmacological Effect of Traditional Chinese Medicine SiJunZiTang on Stress-Induced Peptic Ulcers

Purpose. To explore the effects of SiJunZiTang (SJZT) on central neurotransmitters and the inhibition of HCl hypersecretion, along with the role of the vagus nerve. From this, the effects of SJZT and its constituent ingredients on inhibiting stress-induced peptic ulcers will be determined. Methods. Methods used to determine SJZT's effectiveness included (1) measuring the antipeptic ulcer effects of varying combinations of the constituents of SJZT; (2) evaluations of monoamine (MA) level in the brain; and (3) measuring the effects of longer-term SJZT treatment. Results. Comparing the control and experimental groups where the rats’ vagus nerves were not cut after taking SJZT orally (500 mg/kg and 1000 mg/kg), the volume of enterogastric juice, free HCl and total acidity all reduce dose-dependently. The group administered SJZT at 1000 mg/kg showed significant reductions (P<0.05). For the experimental groups where the vagus nerves were cut, a comparison with the control group suggests that the group receiving SJZT (500 mg/kg) orally for 21 days demonstrated a cure rate of 34.53%. Conclusion. The results display a correlation between the therapeutic effects of SJZT on stress-induced peptic ulcers and central neurotransmitter levels. Further to this, SJZT can inhibit the hypersecretion of HCl in the stomach, thus inhibiting stress-induced peptic ulcers

Serum ferritin levels and polycystic ovary syndrome in obese and nonobese women

AbstractObjectiveThe aim of this study is to evaluate serum ferritin levels and polycystic ovary syndrome (PCOS)-related complications in obese and nonobese women.Materials and methodsThis retrospective study included 539 (286 with PCOS and 253 without PCOS).ResultsSerum ferritin correlated with menstrual cycle length, sex hormone-binding globulin, total testosterone, androstenedione, triglyceride, and total cholesterol in both obese and nonobese women. Obese women with high ferritin levels exhibited higher insulin resistance, impaired glucose tolerance, and liver enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase) than obese women with low ferritin levels. However, among nonobese women, insulin resistance and risk of diabetes were not significantly different between the high and low ferritin groups. Independent of obesity, hypertriglyceridemia was the major metabolic disturbance observed in women with elevated serum ferritin levels.ConclusionElevated serum ferritin levels are associated with increased insulin resistance and risk of diabetes in obese women but not in nonobese women. However, higher serum ferritin levels were correlated with a greater risk of hyperglyceridemia in both obese and nonobese women. Therefore, hypertriglyceridemia in women with PCOS might be associated with iron metabolism

Chemoenzymatic synthesis and structural characterization of 2-O-sulfated glucuronic acid-containing heparan sulfate hexasaccharides

Heparan sulfate and heparin are highly sulfated polysaccharides that consist of a repeating disaccharide unit of glucosamine and glucuronic or iduronic acid. The 2-O-sulfated iduronic acid (IdoA2S) residue is commonly found in heparan sulfate and heparin; however, 2-O-sulfated glucuronic acid (GlcA2S) is a less abundant monosaccharide (∼<5% of total saccharides). Here, we report the synthesis of three GlcA2S-containing hexasaccharides using a chemoenzymatic approach. For comparison purposes, additional IdoA2S-containing hexasaccharides were synthesized. Nuclear magnetic resonance analyses were performed to obtain full chemical shift assignments for the GlcA2S- and IdoA2S-hexasaccharides. These data show that GlcA2S is a more structurally rigid saccharide residue than IdoA2S. The antithrombin (AT) binding affinities of a GlcA2S- and an IdoA2S-hexasaccharide were determined by affinity co-electrophoresis. In contrast to IdoA2S-hexasaccharides, the GlcA2S-hexasaccharide does not bind to AT, confirming that the presence of IdoA2S is critically important for the anticoagulant activity. The availability of pure synthetic GlcA2S-containing oligosaccharides will allow the investigation of the structure and activity relationships of individual sites in heparin or heparan sulfate

Chemoenzymatic synthesis of unmodified heparin oligosaccharides: cleavage of p-nitrophenyl glucuronide by alkaline and Smith degradation

A heparin oligosaccharide having a completely natural structure was successfully synthesized through a chemoenzymatic approach using an unnatural glycosyl acceptor, p -nitrophenyl glucuronide (GlcA- p NP)