Biomedical subjects

Wei Zhang

Publications and source records attributed to Wei Zhang.

At least 163 records · Page 9Linked to original sources

PubMed2006

[Ultrasound-guided minimally invasive neurosurgery in treatment of cranial tumors: clinical study].

OBJECTIVE: To explore the applicability of ultrasound-guided minimally invasive neurosurgery in treatment of intracranial tumors. METHODS: Thirty five patients with intracranial tumors diagnosed with preoperative CT and MRI underwent craniotomy. Intraoperative real-time monitoring ultrasound was conducted to detect the location, size and depth of the cerebral masses so as to determine the appropriate approach. At the end of operation, ultrasonography was used to explore the range of residue tumors. RESULTS: All the 35 patients acquired exact location of the tumors with ultrasound manifesting different levels of echo. According to the pathological results, the lesions of 32 patients (91%) were totally removed and 3 patients (9%) underwent subtotal resection. No infection was found. CONCLUSION: Ultrasound-guided minimally invasive neurosurgery is an effective real-time tool to localize brain tumors. It will provide a significant guidance for minimally invasive neurosurgery.

Adult↗

PubMed2006

Inhibitory effects of blocking voltage-dependent potassium channel 1.3 on human monocyte-derived macrophage differentiation into foam cells.

OBJECTIVE: To investigate the expression of voltage-dependent potassium channel 1.3 (Kv1.3) mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and its function in foam cell formation. METHODS: Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of the human macrophage-derived foam cell model, the expression of Kv1.3 channel was investigated by immunocytochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Furthermore, the effects of rMargatoxin, a Kv 1.3 channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein (OxLDL) were studied. RESULTS: After the macrophages co-incubated with 30 mg/L OxLDL at 37 degrees C for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) in cells markedly increased and the ratio of CE/TC rose from (14.4+/-6.8)% to (57.9+/-3.5)% (n=7, P<0.05). However, the expression of Kv1.3 channel had no significant change. rMargatoxin (0.1 nmol/L and 10 nmol/L) markedly reduced the contents of TC, FC and CE in macrophages and the ratios of CE/TC decreased to (42.8+/-11.6)% and (22.6+/-8.0)%, respectively (n=7, P<0.05). Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased. CONCLUSION: These data clearly show that the expression of Kv1.3 channel does not change obviously during human monocyte-derived macrophage differentiation into foam cells and the blocking of it would prevent foam cell formation.

Adult↗

PubMed2006

[Rheumatoid leptomeningitis: a case report and literature review].

To report the clinical, radiological and neuropathological findings of a patient with rheumatoid meningitis. The patient was a 71-year-old Chinese man with a two-year history of rheumatoid arthritis and no other significant medical history, who presented to our hospital recurrent weakness of his left extremities, dysarthria and a continuous bilateral hand tremor. Cerebrospinal fluid (CSF) and serum examinations were normal apart from a mildly raised serum perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA). Brain magnetic resonance imaging (MRI) showed leptomeningeal enhancement in both frontal and parietal lobes, in addition to several old white matter infarcts. Meningeal biopsy showed numerous infiltrating macrophages and lymphocytes within the leptomeninges. The patient responded clinically and radiologically to corticosteroid and cyclophosphamide therapy. The patient subsequently developed herpes zoster over his left chest as a complication of his immunosuppressive treatment. His cyclophosphamide was ceased and intravenous immunoglobulin (IVIG) therapy was commenced, with good clinical response to both the herpes zoster and meningitis. According to the result of the biopsy, aseptic meningitis was considered the MRI results and the patient's clinical history were given, and a diagnosis of rheumatoid meningitis was made. The patient was p-ANCA positive. Although there was no evidence for cerebral vasculitis on biopsy, it remains a possibility that the patient's recurrent minor cerebral infarcts visible on MRI were vasculitic in nature.

Aged↗

PubMed2006

Emerging multiple mutations and high-level fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus isolated from ocular infections.

We investigated the prevalence of mutations in the gyrA, gyrB, grlA, and grlB genes in 21 clinical isolates of methicillin-resistant Staphylococcus aureus recovered from ocular infections. These isolates were classified into 16 groups on the basis of pulsed-field gel electrophoresis (PFGE) patterns. Among these nonidentical strains, 9 different combinations of mutations were observed. We observed an unusually high frequency of mutations: 10 (62.5%) of the isolates had four or five mutations, 5 (31.3%) of the isolates had double mutations, and 1 isolate had a single mutation. Different mutations were detected in strains of the same PFGE type, and this is consistent with the independent acquisition of mutations. The minimun inhibitory concentrations values ranged from 0.5 to 512 microg/mL for levofloxacin and 0.125 to 128 microg/mL for gatifloxacin. Only 1 isolate was found to be susceptible to both agents. These results suggest that application of high concentration fluoroquinolone ophthalmic solutions selects for isolates presenting such mutations that may result in a high level of resistance to fluoroquinolones.

Drug Resistance, Bacterial↗

PubMed2006

Molecular characteristics of class 1 and class 2 integrons and their relationships to antibiotic resistance in clinical isolates of Shigella sonnei and Shigella flexneri.

OBJECTIVES: To analyse the gene cassettes and determine the roles of class 1 and class 2 integrons in antibiotic-resistant strains of Shigella sonnei (n=31) and Shigella flexneri (n=33). METHODS: Various molecular techniques, including PCR and Southern-blotting analysis, were used to analyse various markers of class 1 and class 2 integrons in these 64 S. sonnei and S. flexneri isolates collected in Hangzhou, China. The gene cassette arrays in integrons were identified by DNA sequencing and/or restriction fragment length polymorphism. Two genomic DNA fragments, one containing intI1 from a S. flexneri isolate that contains intI1 but lacks 3'-conserved region and another containing intI2 from a S. sonnei isolate, were cloned into pUC19 vectors and sequenced. The links between integron gene cassette arrays and antibiotic resistance were analysed. RESULTS: Class 2 integrons were present in 80.6% (25/31) of the S. sonnei isolates and 87.9% (29/33) of the S. flexneri isolates. All of these integron 2-positive isolates contained constant gene cassette arrays of dfrA1+sat1+aadA1 which confer resistance to trimethoprim and streptomycin. It was demonstrated that the class 2 integron was located in the Tn7 region inside the attTn7 locus downstream of glmS in Shigella. Class 1 integrons were found in 9.4% (6/64) of Shigella spp. isolates. An atypical class 1 integron without a 3'-conserved segment on the Shigella chromosome, termed Shigella atypical class 1 integron (SAI), was present in 84.9% (28/33) of S. flexneri isolates. The SAI contained two gene cassettes, bla(OXA30) and aadA1; however, the SAI conferred resistance to ampicillin, but not to streptomycin, in Escherichia coli host. The bla(OXA30) and aadA1 cassettes of the SAI seemed to be always coordinately excised or integrated. CONCLUSIONS: Multiple and complex mechanisms involving mobile genetic elements in class 1 and class 2 integrons and antibiotic resistance have been developed in the evolution of Shigella strains.

Ampicillin Resistance↗

PubMed2006

Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake.

Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

Animals↗

PubMed2006

Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation.

Many signals that regulate cardiomyocyte growth, differentiation and function are mediated via heterotrimeric G proteins, which are under the control of RGS proteins (Regulators of G protein Signaling). Several RGS proteins are expressed in the heart, but so far little is known about their function and regulation. Using adenoviral gene transfer, we conducted the first comprehensive analysis of the capacity and selectivity of the major cardiac RGS proteins (RGS2-RGS5) to regulate central G protein-mediated signaling pathways in adult ventricular myocytes (AVM). All four RGS proteins potently inhibited Gq/11-mediated phospholipase C beta stimulation and cell growth (assessed in neonatal myocytes). Importantly, RGS2 selectively inhibited Gq/11 signaling, whereas RGS3, RGS4 and RGS5 had the capacity to regulate both Gq/11 and Gi/o signaling (carbachol-induced cAMP inhibition). Gs signaling was unaffected, and, contrary to reports in other cell lines, RGS2-RGS5 did not appear to regulate adenylate cyclase directly in AVM. Since RGS proteins can be highly regulated in their expression by many different stimuli, we also tested the hypothesis that RGS expression is subject to G protein-mediated regulation in AVM and determined the specificity with which enhanced G protein signaling alters endogenous RGS expression in AVM. RGS2 mRNA and protein were markedly but transiently up-regulated by enhanced Gq/11 signaling (alpha1-adrenergic stimulation or Galphaq* overexpression), possibly by a negative feedback mechanism. In contrast, the other negative regulators of Gq/11 signaling (RGS3-RGS5) were unchanged. Endogenous RGS2 (but not RGS3-RGS5) expression was also up-regulated in cells with enhanced AC signaling (beta-adrenergic or forskolin stimulation). Taken together, these findings suggest diverse roles of RGS proteins in regulating myocyte signaling. RGS2 emerged as the only selective and highly regulated inhibitor of Gq/11 signaling that could potentially become a promising target for ameliorating Gq/11-mediated signaling and growth.

Adenoviridae↗

PubMed2006

[Detection of Y chromosome microdeletions in patients with severe oligozoospermia and azoospermia].

OBJECTIVE: To explore the clinical significance of azoospermia factor (AZF) region deletion. METHODS: Detection of the Y-link sequence tagged sites in AZF region was conducted by means of 2 multiplex polymerase chain reactions among 80 patients with severe oligozoospermia and 63 patients with azoospermia, totally 143. RESULTS: Twenty-one cases of microdeletion were found among the 143 infertile patients with a prevalence of 14.7%. PCR analysis showed that deletion of the portions of Yq in 12 of the 62 idiopathic infertility patients, 3 being with severe oligozoospermia and 9 with azoospermia, and in 9 out of the 81 patients with non-idiopathic infertility. PCR analysis of 40 normal fertile men did not detect any abnormality. The results of the microdeletion showed that 1 patient had a microdeletion in the AZFa region with sY84 and sY86 (1/21, 4.8%), 2 patients presented a large deletion involving sY127 and sY143 from AZFb, and sY254 and sY255 from AZFc (1/21, 9.5%). Two patients had the deletions located in AZFb region (2/21, 9.5%), and 16 patients had a deletion on the AZFc region involving the DAZ (deleted in azoospermia) gene (16/21, 76.2%) Among the 21 infertile men 4 showed a testicular cytologic picture of maturation arrest, 6 patients had severe hypospermatogenesis, and 11 had Sertoli cell-only syndrome. There were not significant differences in location and extent of deletions between the patients with idiopathic infertility and those with non-idiopathic infertility. CONCLUSION: It is recommended to carry out screening of microdeletion of Y chromosome among the patients with idiopathic and non-idiopathic infertility, especially the candidates for intracytoplasmic sperm injection.

Adult↗

PubMed2006

Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types.

The family of insulin-like growth factor-binding proteins (IGFBPs) comprises six members, which bind and regulate the functions of insulin-like growth factors. Overexpression of IGFBP2 and IGFBP5 contributes to the invasiveness and progression of several human cancers, but their role and clinical significance in ovarian cancer has not been investigated in detail. We examined IGFBP2 and IGFBP5 expression levels using two tissue microarrays, one containing six normal surface epithelium, six benign serous cysts, 10 serous borderline tumors, eight low-grade, and 20 high-grade serous carcinomas. The other comprising 441 ovarian cancers of different histologic types linked to a clinicopathologic database. Each tumor was sampled in duplicate with a 1.0-mm punch core needle. Immunohistochemical staining was performed using antibodies against IGFBP2 or IGFBP5. The staining intensity was scored semiquantitatively as negative (0), weak (1-10%), moderate (10-50%), or strong (50-100%) using computerized image analysis. Statistical analyses used Fisher's exact test and Kaplan-Meier method. IGFBP2 and IGFBP5 were overexpressed in high-grade serous carcinomas compared to normal surface epithelium, benign serous cysts, serous borderline tumors, or low-grade serous carcinoma. They were differentially expressed in different types of ovarian carcinomas, being more often expressed at high levels in high-grade serous carcinoma, malignant mixed mullerian tumors and undifferentiated carcinoma, and more often expressed at low levels or not at all in clear cell and mucinous carcinomas. We concluded that IGFBP2 and IGFBP5 might play a role in the development of high-grade ovarian serous carcinoma, but not in mucinous or clear cell ovarian carcinomas.

Adenocarcinoma, Clear Cell↗

PubMed2006

The relationship between agonist potency and AMPA receptor kinetics.

AMPA-type glutamate receptors are tetrameric ion channels that mediate fast excitatory synaptic transmission in the mammalian brain. When agonists occupy the binding domain of individual receptor subunits, this domain closes, triggering rearrangements that couple agonist binding to channel opening. Here we compare the kinetic behavior of GluR2 channels activated by four different ligands, glutamate, AMPA, quisqualate, and 2-Me-Tet-AMPA, full agonists that vary in potency by up to two orders of magnitude. After reduction of desensitization with cyclothiazide, deactivation decays were strongly agonist dependent. The time constants of decay increased with potency, and slow components in the multiexponential decays became more prominent. The desensitization decays of agonist-activated currents also contained multiple exponential components, but they were similar for the four agonists. The time course of recovery from desensitization produced by each agonist was described by two sigmoid components, and the speed of recovery varied substantially. Recovery was fastest for glutamate and slowest for 2-Me-Tet-AMPA, and the amplitude of the slow component of recovery increased with agonist potency. The multiple kinetic components appear to arise from closed-state transitions that precede channel gating. Stargazin increases the slow kinetic components, and they likely contribute to the biexponential decay of excitatory postsynaptic currents.

Cell Line↗

PubMed2006

Accurate production of time-varying patterns of the moment of force in multi-finger tasks.

We investigated the production of time profiles of the total moment of force produced in isometric conditions by the four fingers of a hand. We hypothesized that these tasks would be associated with multi-finger synergies stabilizing the time profile of the total moment across trials but not necessarily stabilizing the time profile of the total force produced by the fingers. We also expected the multi-finger synergies to prevent an increase in the moment variability with its magnitude. Seated subjects pressed on force sensors with the four fingers of the right hand and produced two time profiles of the total moment of force, starting from a certain pronation effort, leading to a similar supination effort, and back to the initial pronation effort. One of the profiles was a sequence of straight lines (M-Ramp) while the other was a smooth curve (M-Sine). The subjects showed an increase in the total force during each task. This was accompanied by an increase in the force produced by the fingers opposing the required direction of the total moment-antagonist fingers. Variability of the total force and of the total moment showed complex, non-monotonic changes with the magnitude of the force and moment, respectively. In both tasks, the subjects showed patterns of co-variation of commands to fingers that stabilized the required moment profile over trials. The time profile of the total force was stabilized to a lesser degree or not stabilized at all. The share of fingers with larger moment arms (index finger for pronation efforts and little finger for supination efforts) was higher when the fingers acted to produce moments in a required direction but not necessarily when they acted as antagonists. The results demonstrate the existence of multi-finger synergies stabilizing the combined rotational action. They fit a hypothesis that stabilization of rotational actions may be a default strategy conditioned by everyday experience. The data also suggest that the mechanical advantage hypothesis is valid for sets of effectors that act in the required direction but not for sets of effectors that act as antagonists.

Adult↗

PubMed2006

Nanofibril self-assembly of an arylene ethynylene macrocycle.

Nanofibril structures have been fabricated from an arylene ethynylene macrocycle (AEM), which consists of a square frame corner-joined by four carbazole moieties. The fabrication was performed through a gelating process by cooling a warm, homogeneous solution in cyclohexane at high temperature (e.g., 100 degrees C) to room temperature. During the gelation, the molecules become organized, with optimal pi-pi stacking in cooperation with the side-chain association. The favorable pi-pi stacking facilitates the 1D growth of molecular assembly.

Alkynes↗

PubMed2006

[Application of diffusion tensor imaging fractography in minimally invasive surgery of brain tumors].

OBJECTIVE: To investigate the effects and prospect of application of diffusion tensor imaging (DTI) fractography in minimally invasive surgery of brain tumors. METHODS: DTI fractography was performed in 52 patients with malignant brain tumors. Based on the DTI fractography results, 34 of the 52 patients underwent operation under neuro-navigation, and 18 of the 52 patients underwent operation routine minimally invasive craniotomy and tumor resection without neuro-navigation. RESULTS: The rate of total tumor resection was 86.5% (45/52). The mortality was 1.9% (1/52). The disability rate was 11.5% (6/52). No case needed the second operation. CONCLUSION: DTI fractography has raised the minimally invasive neurosurgery to the level of protecting the nuclei and nerve tracts and guiding intra-operative management of infiltration of deep-seated tumors, especially when combined with neuro-navigation and interventional MRI.

Adolescent↗

PubMed2006

Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release.

The purpose of the present study was to investigate the effect of ligustilide on vasodilatation in rat mesenteric artery and the mechanisms responsible for it. Isometric tension of rat mesenteric artery rings was recorded by a sensitive myograph system in vitro. The results showed that ligustilide at concentrations more than 10 microM relaxed potassium chloride (KCl)-preconstricted rat mesenteric artery in a concentration-dependent manner. The vasodilatation effect of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted concentration-response curves induced by KCl, calcium chloride (CaCl(2)), noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This suggests that the vasodilatation effects were most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol, glibenclamide, tetraethylammonium and barium chloride did not affect the vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP sensitive potassium channel, calcium-activated potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation. Ligustilide concentration-dependently inhibited the vasoconstriction induced by NA or CaCl(2) in Ca(2+)-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca(2+) influx through VDCC and ROCC, and intracellular Ca(2+) release from Ca(2+) store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca(2+) released by ligustilide occurred via the ryanodine receptors. Our results suggest that ligustilide induces vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and receptor-mediated Ca(2+) influx and release.

4-Butyrolactone↗

PubMed2006

Liposomal quercetin efficiently suppresses growth of solid tumors in murine models.

PURPOSE: Quercetin is a potent chemotherapeutic drug. Clinical trials exploring different schedules of administration of quercetin have been hampered by its extreme water insolubility. To overcome this limitation, this study is aimed to develop liposomal quercetin and investigate its distribution in vivo and antitumor efficacy in vivo and in vitro. EXPERIMENTAL DESIGN: Quercetin was encapsulated in polyethylene glycol 4000 liposomes. Biodistribution of liposomal quercetin i.v. at 50 mg/kg in tumor-bearing mice was detected by high-performance liquid chromatography. Induction of apoptosis by liposomal quercetin in vitro was tested. The antitumor activity of liposomal quercetin was evaluated in the immunocompetent C57BL/6N mice bearing LL/2 Lewis lung cancer and in BALB/c mice bearing CT26 colon adenocarcinoma and H22 hepatoma. Tumor volume and survival time were observed. The mechanisms underlying the antitumor effect of quercetin in vivo was investigated by detecting the microvessel density, apoptosis, and heat shock protein 70 expression in tumor tissues. RESULTS: Liposomal quercetin could be dissolved in i.v. injection and effectively accumulate in tumor tissues. The half-time of liposomal quercetin was 2 hours in plasma. The liposomal quercetin induced apoptosis in vitro and significantly inhibited tumor growth in vivo in a dose-dependent manner. The optimal dose of liposomal quercetin resulted in a 40-day survival rate of 40%. Quantitative real-time PCR showed that liposomal quercetin down-regulated the expression of heat shock protein 70 in tumor tissues. Immunohistochemistry analysis showed that liposomal quercetin inhibited tumor angiogenesis as assessed by CD31 and induced tumor cell apoptosis. CONCLUSIONS: Our data indicated that pegylated liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be a potential application in the treatment of tumor.

Adenocarcinoma↗

PubMed2006

Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males.

BACKGROUND: Rosuvastatin, a novel potent HMG-CoA reductase inhibitor, is excreted into bile mediated by breast cancer resistance protein (BCRP). Our objective was to determine the association between the most frequent single nucleotide polymorphisms (SNPs) of the BCRP (421C>A) and the pharmacokinetics of rosuvastatin. METHOD: Pre-screening of SLCO1B1 521TC and CYP2C9*1/*3 were performed before this pharmacokinetic study. Fourteen healthy volunteers who are SLCO1B1 521TT and CYP2C9*1/*1 wild-type homozygotes were selected to participate in this study. Seven were 421CC wild-type of BCRP, the others were carriers with at least one 421C>A mutant allele (five subjects had a genotype of 421CA and two were homozygotes of 421AA). Each was given a single oral dose of 20 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured for up to 72 h by LC-MS. RESULTS: The pharmacokinetic parameters of rosuvastatin showed a significantly difference between the two genotyped groups. The AUC(0-72) and AUC(0-infinity) of rosuvastatin were lower in the 421CC group than in the 421CA+421AA group (33.8+/-11.4 vs. 59.6+/-22.2 ng.h/ml, P=0.018; 34.9+/-11.9 vs. 62.2+/-23.5 ng.h/ml, P=0.018), respectively. The C(max) value was higher in the 421CA+421AA group than that in the 421CC group (9.9+/-5.4 vs. 5.1+/-2.4 ng/ml, P=0.048). The CL/F value was lower in the 421CA+421AA group than that in the 421CC group (384.7+/-161.2 vs. 674.0+/-297.6 l/h, P=0.043). The T(1/2) and T(max) values showed no difference between these groups. CONCLUSIONS: The BCRP 421C>A polymorphism may play an important role in the pharmacokinetics of rosuvastatin in healthy Chinese males after the exclusion of impact of SLCO1B1 and CYP2C9 genetic polymorphism.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2006

Pten regulates neuronal arborization and social interaction in mice.

CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.

Animals↗

PubMed2006

Strike a balance: optimization of backbone torsion parameters of AMBER polarizable force field for simulations of proteins and peptides.

Based on the AMBER polarizable model (ff02), we have re-optimized the parameters related to the main-chain (Phi, Psi) torsion angles by fitting to the Boltzmann-weighted average quantum mechanical (QM) energies of the important regions (i.e., beta, P(II), alpha(R), and alpha(L) regions). Following the naming convention of the AMBER force field series, this release will be called ff02pol.rl The force field has been assessed both by energetic comparison against the QM data and by the replica exchange molecular dynamics simulations of short alanine peptides in water. For Ace-Ala-Nme, the simulated populations in the beta, P(II) and alpha(R) regions were approximately 30, 43, and 26%, respectively. For Ace-(Ala)(7)-Nme, the populations in these three regions were approximately 24, 49, and 26%. Both were in qualitative agreement with the NMR and CD experimental conclusions. In comparison with the previous force field, ff02pol.rl demonstrated good balance among these three important regions. The optimized torsion parameters, together with those in ff02, allow us to carry out simulations on proteins and peptides with the consideration of polarization.

Computer Simulation↗