Biomedical subjects

Wen Jiang

Publications and source records attributed to Wen Jiang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Fast rotational matching of single-particle images.

The presence of noise and absence of contrast in electron micrographs lead to a reduced resolution of the final 3D reconstruction, due to the inherent limitations of single-particle image alignment. The fast rotational matching (FRM) algorithm was introduced recently for an accurate alignment of 2D images under such challenging conditions. Here, we implemented this algorithm for the first time in a standard 3D reconstruction package used in electron microscopy. This allowed us to carry out exhaustive tests of the robustness and reliability in iterative orientation determination, classification, and 3D reconstruction on simulated and experimental image data. A classification test on GroEL chaperonin images demonstrates that FRM assigns up to 13% more images to their correct reference orientation, compared to the classical self-correlation function method. Moreover, at sub-nanometer resolution, GroEL and rice dwarf virus reconstructions exhibit a remarkable resolution gain of 10-20% that is attributed to the novel image alignment kernel.

Algorithms↗

PubMed2005

Involvement of extracellular regulated kinase and p38 kinase in hippocampal seizure tolerance.

The mechanisms underlying brain seizure tolerance, a phenomenon in which brief periods of seizures protect brain against the lethal effects of subsequent sustained seizures, are poorly understood. Because brain seizure tolerance and brain ischemia tolerance likely share certain common mechanisms, the recent evidence that activation of extracellular regulated kinase (ERK) and p38 kinase pathways plays a critical role in ischemic preconditioning suggests that a similar mechanism may underlie brain seizure tolerance. We investigated the hypothesis in a rat kainic acid preparation of seizure preconditioning and tolerance, which was established by induction of one episode of priming epileptic status lasting for 20 min on the first day and another episode of sustained epileptic status lasting for 2 hr on the second day. We observed that acute seizures lead to a rapid activation of ERK and p38 in the hippocampal CA3 area, the brain region most susceptible to the lethal effects of epileptic status. Pretreatment with the ERK inhibitor PD98059 and the p38 inhibitor SB203580 selectively reduces seizure-elicited activation of ERK and p38, respectively, and significantly reduces priming seizure-induced protection of CA3 neurons. These findings indicate that, similar to brain ischemia tolerance, brain seizure tolerance also involves the ERK and p38 signaling pathways.

Animals↗

PubMed2005

Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors.

A novel series of competitive, reversible cathepsin S (CatS) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of CatS inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S.

Animals↗

PubMed2005

Surface-plasmon-coupled emission of quantum dots.

We studied surface plasmon-coupled emission (SPCE) of semiconductor quantum dots (QDs). These QDs are water-soluble ZnS-capped CdSe nanoparticles stabilized using lysine cross-linked mercaptoundecanoic acid. The QDs were spin-coated from 0.75% PVA solution on a glass slide covered with 50 nm of silver and a 5-nm protective SiO(2) layer. Excited QDs induced surface plasmons in a thin silver layer. Surface plasmons emitted a hollow cone of radiation into an attached hemispherical glass prism at a narrow angle of 48.5 degrees. This directional radiation (SPCE) preserves the spectral properties of QD emission and is highly p-polarized irrespective of the excitation polarization. The SPCE spectrum depends on the observation angle because of the intrinsic dispersive properties of SPCE phenomenon. The remarkable photostability can make QDs superior to organic fluorophores when long exposure to the intense excitation is needed. The nanosize QDs also introduce a roughness near the metal layer, which results in a many-fold increase of the coupling of the incident light to the surface plasmons. This scattered incident illumination transformed into directional, polarized radiation can be used simultaneously with SPCE to develop devices based on both quantum dot emission and light scattered from surface plasmons on a rough surface.

Cadmium Compounds↗

PubMed2005

Topiramate therapy for paroxysmal kinesigenic choreoathetosis.

We observed the clinical efficacy of topiramate for paroxysmal kinesigenic choreoathetosis (PKC). Topiramate was administered as a monotherapy with titrated dosages to 8 patients with PKC. Target daily dose of topiramate was 100 to 200 mg; the follow-up period ranged from 8 months to 2 years. All of the patients became attack-free, and side effects were mild. The results show that topiramate is effective as a monotherapy for treating patients with PKC. The response to topiramate indicates that the disease may be caused by an ion channel defect.

Adolescent↗

PubMed2005

Electron cryomicroscopy of single particles at subnanometer resolution.

Electron cryomicroscopy and single-particle reconstruction have advanced substantially over the past two decades. There are now numerous examples of structures that have been solved using this technique to better than 10 A resolution. At such resolutions, direct identification of alpha helices is possible and, often, beta-sheet-containing regions can be identified. The most numerous subnanometer resolution structures are the icosahedral viruses, as higher resolution is easier to achieve with higher symmetry. Important non-icosahedral structures solved to subnanometer resolution include several ribosome structures, clathrin assemblies and, most recently, the Ca2+ release channel. There is now hope that, in the next few years, this technique will achieve resolutions approaching 4 A, permitting a complete trace of the protein backbone without reference to a crystal structure.

Animals↗

PubMed2005

Electron cryomicroscopy of biological machines at subnanometer resolution.

Advances in electron cryomicroscopy (cryo-EM) have made possible the structural determination of large biological machines in the resolution range of 6-9 angstroms. Rice dwarf virus and the acrosomal bundle represent two distinct types of machines amenable to cryo-EM investigations at subnanometer resolutions. However, calculating the density map is only the first step, and much analysis remains to extract structural insights and the mechanism of action in these machines. This paper will review the computational and visualization methodologies necessary for analysis (structure mining) of the computed cryo-EM maps of these machines. These steps include component segmentation, averaging based on local symmetry among components, density connectivity trace, incorporation of bioinformatics analysis, and fitting of high-resolution component data, if available. The consequences of these analyses can not only identify accurately some of the secondary structure elements of the molecular components in machines but also suggest structural mechanisms related to their biological functions.

Capsid Proteins↗

PubMed2005

Common ancestry of herpesviruses and tailed DNA bacteriophages.

Comparative analysis of capsid protein structures in the eukaryote-infecting herpesviruses (Herpesviridae) and the prokaryote-infecting tailed DNA bacteriophages (Caudovirales) revealed a characteristic fold that is restricted to these two virus lineages and is indicative of common ancestry. This fold not only serves as a major architectural element in capsid stability but also enables the conformational flexibility observed during viral assembly and maturation. On the basis of this and other emerging relationships, it seems increasingly likely that the very diverse collection of extant viruses may have arisen from a relatively small number of primordial progenitors.

Capsid↗

PubMed2005

[The features of auditory brainstem response in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the effects and causes of obstructive sleep apnea-hypopnea syndrome (OSAHS) on auditory pathway, the changes of auditory brainstem response (ABR) were analyzed. METHOD: With the use of polysomnography,72 snorers were examined and divided into OSAHS and non- OSAHS groups. These two groups patients and a group of normal person were underwent ABR measuring. RESULT: There were statistically significant difference between the group of OSAHS and the non-OSAHS or the group of OSAHS and the normals on the delayed latency of wave I and wave V, the response liminal value of wave V rised. CONCLUSION: The results suggest that cochlear function may be affected in patient with OSAHS, the effected of brain stem is unknown.

Adult↗

PubMed2004

Ionotropic glutamate receptor antagonists inhibit the proliferation of granule cell precursors in the adult brain after seizures induced by pentylenetrazol.

Seizures have been shown to promote the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we examined the effects of selective ionotropic glutamate receptor antagonists on granule cell precursor proliferation in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. We found that the NMDA receptor antagonist MK-801 significantly inhibited behavioral and EEG seizures and completely blocked seizure-induced increase in the number of BrdU-labeled cells in the dentate gyrus. Although the AMPA/KA receptor antagonist DNQX was not observed to affect seizures, it significantly suppressed the number of BrdU-labeled cells in the dentate gyrus. Double immunohistochemical staining showed that both the mature granule cells and the majority of BrdU-labeled, mitotically active cells expressed the NMDA receptor subunit NR1 and the AMPA/KA receptor subunit GluR2. Because accumulated evidence showed that mild seizures are sufficient to promote precursor cell proliferation, the present findings that MK-801 inhibited seizures and completely blocked seizure-induced increase in precursor cell proliferation suggest that the direct blockade action of MK-801 on NMDA receptors on the granule cell precursors may play an important role in blocking seizure-induced precursor cell proliferation. The suppression of seizure-induced proliferation of granule cell precursors by DNQX may be achieved by the direct action of DNQX on AMPA/KA receptors on the granule cell precursors. Thus, our findings indicate that seizures may promote cell proliferation in the adult rat dentate gyrus through glutamatergic mechanisms acting on both NMDA and AMPA/KA receptors.

Animals↗

PubMed2004

Effects of nitric oxide on dentate gyrus cell proliferation after seizures induced by pentylenetrazol in the adult rat brain.

Epileptic seizures have been shown to increase the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. This study examined the effect of nitric oxide (NO) on the proliferation of granule cell precursors in adult rats after pentylenetrazol (PTZ)-induced generalized clonic seizures. Using systemic bromodeoxyuridine (BrdU) to label dividing cells, we found that injection of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (50 mg/kg i.p.) 10 min before PTZ significantly reduced the number of BrdU labeled cells in the dentate gyrus 3, 7, and 14 days after seizures (P < 0.05). Administration of the inducible NOS (iNOS) inhibitor aminoguanidine (100 mg/kg i.p.) also significantly inhibited the proliferation rate of neural precursor cells in the dentate gyrus at various time points after PTZ-induced seizures. Our findings suggest that epileptic seizures lead to increased cell proliferation in the adult rat dentate gyrus through NO-dependent mechanisms. Both the NO originating from nNOS and iNOS may be involved in brain repair after seizures.

Animals↗

PubMed2004

Response of seizure-induced newborn neurons in the dentate gyrus of adult rats to second episode of seizures.

In this study we examined the unknown issue of whether seizure-induced newborn hippocampal neurons in freely moving adult rats are able to respond to pathophysiological stimuli in the same way as their neighboring neurons do. Three days after pentylenetrazol (PTZ)-induced generalized seizures, rats received 5-bromodeoxyuridine (BrdU) injections to label dividing cells, followed 4 weeks later by the second PTZ injection to induce second episode of generalized seizures. We observed that the first episode of PTZ-induced seizures resulted in a significant increase in the number of newborn neurons in the adult hippocampal dentate gyrus. In comparison with vehicle-injected control rats that exhibited no Fos immunoreactivity and mild glutamic acid decarboxylase 67 (GAD67) expression in the dentate granule cells, rats killed 2-6 h following the second PTZ injection showed intensive Fos and GAD67 expression in virtually all granule cells with or without BrdU double-labeling. These findings provide important evidence indicating that seizure-induced newborn neurons in freely moving adult rats are able to respond to pathophysiological stimuli in the same way as neighboring neurons do.

Animals↗

PubMed2004

Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN.

The tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid and protein phosphatase. We report here that PTEN physically associates with the NR1 and NR2B subunits of NMDA receptors (NMDARs) in rat hippocampus. Downregulating the protein expression of PTEN inhibits the function of extrasynaptic NMDARs and decreases NMDAR surface expression, suggesting a crucial role for endogenous PTEN in the modulation of NMDAR-mediated neuronal function. Reducing PTEN expression also enhances Akt/Bad phosphorylation in hippocampal neurons. Importantly, suppressing lipid and protein phosphatase activity of PTEN, respectively, activates Akt and inhibits extrasynaptic NMDAR activity and thereby protects against ischemic neuronal death in vitro and in vivo. Thus, our study reveals a dual neuroprotective mechanism by which Akt/Bad and extrasynaptic NMDARs are regulated via downregulation of two distinct PTEN phosphatase activities and present the possibility of PTEN as a potential therapeutic target for stroke treatment.

Animals↗

PubMed2004

A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties.

Histamine mediates its physiological function through binding to four known histamine receptors. Here, we describe the first selective antagonist of the histamine H4 receptor, the newest member of the histamine receptor family, and provide evidence that such antagonists have anti-inflammatory activity in vivo. 1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine (JNJ 7777120) has a K(i) of 4.5 nM versus the human receptor and a pA(2) of 8.1. It is equipotent against the human, mouse, and rat receptors. It exhibits at least 1000-fold selectivity over H1, H2, or H3 receptors and has no cross-reactivity against 50 other targets. This compound has an oral bioavailability of approximately 30% in rats and 100% in dogs, with a half-life of approximately 3 h in both species. JNJ 7777120 blocks histamine-induced chemotaxis and calcium influx in mouse bone marrow-derived mast cells. In addition, it can block the histamine-induced migration of tracheal mast cells from the connective tissue toward the epithelium in mice. JNJ 7777120 significantly blocks neutrophil infiltration in a mouse zymosan-induced peritonitis model. This model is reported to be mast cell-dependent, which suggests that the compound effect may be mediated by mast cells. These results indicate that the histamine H4 receptor plays a role in the inflammatory process. Selective H4 receptor antagonists like JNJ 7777120 may have the potential to be useful in treating inflammation in humans.

Animals↗

PubMed2004

A 9 angstroms single particle reconstruction from CCD captured images on a 200 kV electron cryomicroscope.

Sub-nanometer resolution structure determination is becoming a common practice in electron cryomicroscopy of macromolecular assemblies. The data for these studies have until now been collected on photographic film. Using cytoplasmic polyhedrosis virus (CPV), a previously determined structure, as a test specimen, we show the feasibility of obtaining a 9 angstroms structure from images acquired from a 4 k x 4 k Gatan CCD on a 200 kV electron cryomicroscope. The match of the alpha-helices in the protein components of the CPV with the previous structure of the same virus validates the suitability of this type of camera as the recording media targeted for single particle reconstructions at sub-nanometer resolution.

Cryoelectron Microscopy↗

PubMed2004

Semiconductor quantum dots as contrast agents for whole animal imaging.

Recent developments in quantum dot (QD) technology have paved the way for using QDs as optical contrast agents for in vivo imaging. Pioneering papers showed the use of QDs as luminescent contrast agents for imaging cancer and guiding cancer surgery. The possible future use of QDs for clinical applications is expected to have a significant impact, however many challenges in this field have yet to be overcome.

Contrast Media↗

PubMed2004

[Relationship between adenoids hypertrophy and secretory otitis media].

OBJECTIVE: To investigae the cause of secretory otitis media resulting from adenoids hypertrophy and the relationship between adenoids hypertrophy and secretory otitis media. METHOD: According to the grades of adenoids hypertrophy, 140 children were divided into two groups: the group of middle-grade and the group of pathological hypertrophy. The effect about the degree of adenoids hypertrophy resulted in the descendent of middle ear function and the difference of incidence of secretory otitis media were analyzed. RESULT: The incidence of secretory otitis media and the pattern of tympanic press were distinct difference in two groups. CONCLUSION: The results suggested that there was a positive correlation among the grades of adenoids hypertrophy, the descendent degree of middle ear function and the incidence of secretory otitis media.

Adenoids↗

PubMed2004

[Association between the shape alteration of pharyngeal ostium of eustachian tube and secretory otitis media].

OBJECTIVE: To investigate the association between the shape alteration of pharyngeal ostium of eustachian tube and secretory otitis media (SOM). METHOD: Two hundred and twelve pharyngeal ostiums of eustachian tube were observed by using rhinopharyngoscope and divided into two groups: the contrast's and the secretory otitis media's, and all the shape of pharyngeal ostium of eustachian tube were divided into triangular type, cravice type, elliptical type and bell type. RESULT: The shape of pharyngeal ostium of eustachian tube are remarkablely difference with the normal group and the diseased group. There are 84 cases triangular type (73%), 4 cases cravice type (3.5%), 17 cases bell type (8.7%) and 10 cases elliptical type (14.8%) in the former. There are 13 cases triangular type (13.4%), 68 cases cravice type (3.5%), 5 cases elliptical type (5.2%) and 11 cases bell type (11.3%) in the SOM group. CONCLUSION: The study suggest that there is a close association between the shape alteration of pharyngeal ostium of eustachian tube and secretory otitis media, meanwhile it offer a new index for exploring the new methods to cure the adult secretory otitis media how to resume the normal shape and the function of pharyngeal ostium of eustachian tube as soon as possible early.

Adolescent↗