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Jing Hu

Publications and source records attributed to Jing Hu.

At least 55 records · Page 3Linked to original sources

Closed-loop cortical control of direction using support vector machines.

Motor neuroprosthetics research has focused on reproducing natural limb motions by correlating firing rates of cortical neurons to continuous movement parameters. We propose an alternative system where specific spatial-temporal spike patterns, emerging in tasks, allow detection of classes of behavior with the aid of sophisticated nonlinear classification algorithms. Specifically, we attempt to examine ensemble activity from motor cortical neurons, not to reproduce the action this neural activity normally precedes, but rather to predict an output supervisory command to potentially control a vehicle. To demonstrate the principle, this design approach was implemented in a discrete directional task taking a small number of motor cortical signals (8-10 single units) fed into a support vector machine (SVM) to produce the commands Left and Right. In this study, rats were placed in a conditioning chamber performing a binary paddle pressing task mimicking the control of a wheelchair turning left or right. Four animal subjects (male Sprague-Dawley rats) were able to use such a brain-machine interface (BMI) with an average accuracy of 78% on their first day of exposure. Additionally, one animal continued to use the interface for three consecutive days with an average accuracy over 90%.

Algorithms↗

Feature detection in motor cortical spikes by principal component analysis.

Principal component analysis was performed on recorded neural spike trains in rats' motor cortices when rats were involved in real-time control tasks using brain-machine interfaces. The rat with implanted microelectrode array was placed in a conditioning chamber, but freely moving, to decide which one of the two paddles should be activated to shift the cue light to the center. It is found that the principal component feature vectors revealed the importance of individual neurons and windows of time in the decision making process. In addition, one of the first principal components has much higher discriminative capability than others, although it represents only a small percentage of the total variance in the data. Using one to six principal components with a Bayes classifier achieved classification accuracy comparable to that obtained by a more sophisticated high performance support vector classifier.

Action Potentials↗

Mutation of the SP1 sequence impairs both multimerization and membrane-binding activities of human immunodeficiency virus type 1 Gag.

The Gag protein of human immunodeficiency virus type 1 contains a 14-amino-acid region, termed SP1, between the capsid and downstream nucleocapsid sequences. Although SP1 is known to be indispensable for virus production, the mechanisms involved are mostly unclear. In this study, we demonstrate that an M368A mutation within SP1 severely diminished the ability of Gag to associate with cellular membranes. Although wild-type levels of membrane binding were restored to the M368A Gag by a second-site L20K mutation within matrix, the resultant Gag mutant L20K-M368A remained defective in virus production. This latter deficit was partially consequent to the binding of L20K-M368A Gag to nonraft membranes as opposed to raft association seen for wild-type Gag. Further analysis revealed that the majority of membrane-bound M368A Gag proteins were small oligomers, indicating a multimerization defect. In support of this observation, purified recombinant Gag derivatives containing the M368A mutation formed much lower amounts of high-molecular-weight complexes that were pelletable at 21,000 x g than did wild-type Gag. Based on the myristyl switch model, we propose that the M368A mutation inhibits Gag multimerization and, as a result, restricts the binding of Gag to cellular membranes.

Animals↗

Histone deacetylase inhibition down-regulates cyclin D1 transcription by inhibiting nuclear factor-kappaB/p65 DNA binding.

Histone deacetylase (HDAC) inhibitors are emerging as a promising new class of cancer therapeutic agents. HDAC inhibitors relieve the deacetylation of histone proteins. However, little is known about the nonhistone targets of HDAC inhibitors and their roles in gene regulation. In this study, we addressed the molecular basis of the down-regulation of the nuclear factor-kappaB (NF-kappaB)-responsive gene cyclin D1 by the HDAC inhibitor trichostatin A in mouse JB6 cells. Cyclin D1 plays a critical role in cell proliferation and tumor progression. Trichostatin A inhibits cyclin D1 expression in a NF-kappaB-dependent manner in JB6 cells. Electrophoretic mobility shift assay studies showed that trichostatin A treatment prevents p65 dimer binding to NF-kappaB sites on DNA. Moreover, a chromatin immunoprecipitation assay shows that trichostatin A treatment inhibits endogenous cyclin D1 gene transcription by preventing p65 binding to the cyclin D1 promoter. However, acetylation of p65 is not affected by trichostatin A treatment. Instead, trichostatin A enhances p52 acetylation and increases p52 protein level by enhancing p100 processing. This is the first report that trichostatin A, a HDAC inhibitor, activates p100 processing and relieves the repression of p52 acetylation. The enhanced acetylation of p52 in the nuclei may operate to cause nuclear retention of p65 by increasing the p52/p65 interaction and preventing IkappaBalpha-p65 binding. The enhanced p52 acetylation coincides with decreased p65 DNA binding, suggesting a potential role of p52 acetylation in NF-kappaB regulation. Together, the results provide the first demonstration that HDAC inhibitor trichostatin A inhibits cyclin D1 gene transcription through targeting transcription factor NF-kappaB/p65 DNA binding. NF-kappaB is therefore identified as a transcription factor target of trichostatin A treatment.

Acetylation↗

[Pre- and post-surgical orthodontic treatment of mandibular asymmetry and prognathism].

OBJECTIVE: The purpose of this study was to analyze the pre- and post surgical orthodontic treatment of mandibular asymmetry and prognathism in our hospital, and to summarize some helpful experiences for future clinical work. METHODS: The data were derived from 21 adults aged from 19 - 28 years who had severe mandibular asymmetry and prognathism. The ANB angle of all patients is from -3 degrees to -8 degrees. The value of wits of all patients is from -7 mm to -14 mm. The deviation of chin point of all patients is from 3 mm to 7 mm. RESULTS: The duration of pre- and post-surgical orthodontic treatment was 10-20 months (mean 18 months) and 5-10 months (mean 7.5 months), respectively. The keys in pre-surgical orthodontic treatment include (1) three dimensional dental decompensation; (2) arch form and transverse discrepancy correction; (3) model surgery and the splint making. The main objective of post surgical orthodontic treatment is to detail the occlusion. CONCLUSIONS: Pre- and post surgical orthodontic treatment is essential for the orthognathic treatment of patients with mandibular asymmetry and prognathism.

Adult↗

[Rehabilitation therapy after nasal endoscopic surgery for nasal polyp and chronic sinusitis patients].

OBJECTIVE: To analyze the possible factors affecting the results of nasal endoscopic surgery in nasal polyp and chronic sinusitis patients and to discuss the ways to improve the results of operation. METHOD: Retrospective analysis was done in 226 patients followed up more than 3 year. The analysis was focused on patients' occupation, personal habits, extent of persisting on rehabilitation therapy after operation and clinical recovery status. RESULT: The patients who work in the environment rich of irritating substance and dust,the patients having unhealthy habits (e. g: spicy food and alcohol addicting) and the patients who did not take or insist on rehabilitation therapy after operation (e. g: local and systemic medication, nasal lavage and cleaning up of surgical cavities under nasal endoscope) had higher frequency of relapse and quicker recurrence. Rehabilitation therapy was the most important factor affecting the results of operation. CONCLUSION: Insisting on systemic rehabilitation therapy after operation is a occupation protection and kicking the unhealthy personal habits can prevent and reduce the recurrence of nasal polyp and chronic sinusitis after nasal endoscopic surgery.

Adolescent↗

[The changes of cytoskeleton F-actin in rat bone marrow mesenchymal stem cells and calvarial osteoblasts under mechanical strain].

OBJECTIVE: To explore the response of rat bone marrow mesenchymal stem cells (MSCs and calvarial osteoblasts to mechanical strain and the consequent changes of cytoskeleton F-actin. METHODS: Bone marrow MSCs and calvarial osteoblasts were isolated from SD rats and cultured in vitro. Mechanical stretch was performed on passage 3 cells at 2 000 microepsilon for 0, 2, 6 and 12 hours using four-point bending system. The response of cells and the distribution of F-actin were observed using fluorescent staining under laser scanning confocal microscope and the morphological parameters were quantified using image analysis software Laserpix. RESULTS: Under mechanical stretch, the fluorescent staining decreased obviously at both MSCs and osteoblasts, and F-actin filaments were rearranged and became tenuous, thinner, and abnormally distributed. The outline of nucleus became unclear and apoptotic changes were observed at some of both cells. Cellular size decreased more significantly in MSCs than in osteoblasts. Quantity analysis showed that total area of cells, total fluorescent density and green fluorescent density (F-actin) were all significantly decreased in MSCs (P < 0.05 or P < 0.01), and total fluorescent density, green fluorescent density and red fluorescent density (nuclei) did also in osteoblasts (P < 0.05 or P < 0.01). CONCLUSION: Mechanical stretch caused extensive response on both MSCs and osteoblasts which led to the rearrangement of F-actin filament and apoptosis in some of these cells. MSCs were more sensitive to mechanical strain than osteoblasts.

Actin Cytoskeleton↗

[Quantitative histomorphometric observation of distraction osteogenesis during mandibular lengthening].

PURPOSE: To evaluate the regenerating bone during mandibular distraction osteogenesis by bone histomorphometry combining tetracycline bone labeling fluorescence microscopy. METHODS: Osteotomy was performed on bilateral mandibles in ten goats. A custom-made distractor was applied to lengthen the mandible at a rate of 1 mm/d (0.5 mm/12 hrs) for ten days. Every two animals were sacrificed at 10 d, 15 d, 25 d, 35 d and 45 d postoperatively. Two additional goats were used as normal control. The bony specimens were collected and prepared for bone histomorphometry and tetracycline bone labeling fluorescence microscopy with analysis of variance. RESULTS: From 10 days subgroup to 45 days subgroup, bone volume fraction,trabecular thickness,trabecular number and volume density were gradually increased (P<0.05), while trabecular separation distance and surface density were gradually decreased (P<0.05). Between 15 days subgroup and 45 days subgroup,the index of osteoblast was significantly higher than normal control (P<0.05) and index of osteoclast was increased gradually (P<0.05). Compared with normal control, bone formation rate was accelerated by thousand times between 15 days subgroup and 45 days subgroup (P<0.05). CONCLUSIONS: During the process of mandibular distraction osteogenesis, the bone formation is active, the newly formed bone trabecula gradually become mature, and the remodeling activities of regenerated bone are enhanced gradually. The rate of bone formation within distraction period is faster than consolidation period.

Animals↗

[Construction and characterization of mutant Enteroaggregative E. coli O42 strain with high-pathogenicity island deletion].

OBJECTIVE: To construct and characterize a mutant Enteroaggregative E. coli(EAggEC) O42 strain with in-frame deletion of high-pathogenicity island (HPI). METHODS: The kanamycin resistance gene (kan) was inserted between the sequences of irp8 and irp5 genes as the two homologous sequences for construction of the recombinant plasmid pCO85 by subcloning the recombined sequence into the suicide vector pCVD442. By homologous recombination and conjunction mobilization, EAO85 mutant with deletion of the core region of HPI about 24 kb spanning from irp8 to irp5 sequences was screened. RESULTS: Irp8 and irp5 genes of EAggEC O42 were exchanged by pCO85 by conjunction mobilization with the selection by sucrose. The EAO85 mutant was identified by their failure to yield PCR products with primers specific for the internal regions of HPI. CONCLUSION: We have successfully constructed a mutant of EAggEC O42 strain with HPI in-frame deletion, which may facilitate the exploration of the role of HPI in EAggEC strain.

Bacterial Adhesion↗

[Construction of recombinant plasmid pEGFP-BMP7 and its expression in rat bone marrow mesenchymal stem cells in vitro].

OBJECTIVE: To construct recombinant plasmid pEGFP-BMP7 and determine its expression in rat bone marrow mesenchymal stem cells (MSCs) in vitro. METHODS: cDNA of target gene was obtained from neonatal rat kidney by RT-PCR. After sequencing the target gene, the cDNA was subcloned into a eukaryote plasmid pEGFP-N1 by directed cloning and then digested with two restrictive endonucleases to verify the correctiveness of the recombinant plasmid pEGFP-BMP7. Rat bone marrow MSCs were transiently transfected with the pEGFP-BMP7 and transfection efficiency of the Green Fluorescent Protein (GFP) was determined. RT-PCR and immunocytochemical analysis were also performed to detect the expression of BMP7 in rat MSCs. RESULTS: 1 311 bp cDNA fragment was obtained by RT-PCR and sequence analysis showed it matched perfectly with that of rat BMP7 gene except a single nucleotide change at 756 bp from T to A. Digestion of the recombinant plasmid showed two 1.3 kb and 4.7 kb fragments and their size were same as those of BMP7 and pEGFP. This indicated that BMP7 cDNA was successfully subcloned into pEGFP. Transient transfection showed an efficiency of 33% at day 2 in rat MSCs. After transfection, transcription of BMP7 was detected in MSCs and expression of BMP7 protein was also verified. CONCLUSION: Recombinant eukaryote plasmid pEGFP-BMP7 was successfully constructed and expressed in rat bone marrow MSCs. This procedure may provide a unique method for stimulation of callus formation in distraction osteogenesis and reconstruction of craniofacial bone defects.

Animals↗

Insufficient p65 phosphorylation at S536 specifically contributes to the lack of NF-kappaB activation and transformation in resistant JB6 cells.

NF-kappaB activation is required for TNF-alpha-induced transformation of JB6 mouse epidermal cells. Deficient activation of p65 contributes to the lack of NF-kappaB activation in transformation-resistant (P-) cells. We hypothesized that the differential NF-kappaB activation involves differential p65 phosphorylation arising from enzyme activity differences. Here we show that TNF-alpha induces greater ERK-dependent p65 phosphorylation at S536 in transformation sensitive (P+) cells than in P- cells. Our results establish that limited ERK content contributes to a low IkappaB kinase (IKKbeta) level, in turn resulting in insufficient p65 phosphorylation at S536 upon TNF-alpha stimulation in P- cells. Phosphorylation of p65 at S536 appears to play a role in TNF-alpha-induced p65 DNA binding and recruitment of p300 to the p65 complex as well as in release of p65 bound to HDAC1 and 3. Blocking p65 phosphorylation at S536, but not at S276 or S529, abolishes p65 transactivational activity. Over-expression of p65 but not p65 phosphorylation mutant (S536A) in transformation-resistant P- cells renders these cells sensitive to TNF-alpha-induced transformation. Over-expression of p65 phosphorylation mimics p65-S536D or p65-S536E in P- cells and also rescues the transformation response. These findings provide direct evidence that phosphorylation of p65 at S536 is required for TNF-alpha-induced NF-kappaB activation in the JB6 transformation model. The lack of NF-kappaB activation seen in P- cells can be attributed to an insufficient level of p65 phosphorylation on S536 that arises from insufficient IKKbeta that in turn arises from insufficient ERK. Thus, p65 phosphorylation at S536 offers a potential molecular target for cancer prevention.

Active Transport, Cell Nucleus↗

Dominant-negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation.

Activation of the transcription factor AP-1 (activator protein-1) is required for tumor promotion and maintenance of malignant phenotype. A number of AP-1-regulated genes that play a role in tumor progression have been identified. However, AP-1-regulated genes driving tumor induction are yet to be defined. Previous studies have established that expression of a dominant-negative c-Jun (TAM67) inhibits phorbol 12-tetradecanoyl-13-acetate (TPA)-induced AP-1 transactivation as well as transformation in mouse epidermal JB6/P+ cells and tumor promotion in mouse skin carcinogenesis. In this study, we utilized the tumor promotion-sensitive JB6/P+ cells to identify AP-1-regulated TAM67 target genes and to establish causal significance in transformation for one target gene. A 2700 cDNA microarray was queried with RNA from TPA-treated P+ cells with or without TAM67 expression. Under conditions in which TAM expression inhibited TPA-induced transformation, microarray analysis identified a subset of six genes induced by TPA and suppressed by TAM67. One of the identified genes, the high-mobility group protein A1 (Hmga1) is induced by TPA in P+, but not in transformation-resistant P cells. We show that TPA induction of the architectural transcription factor HMGA1 is inhibited by TAM67, is extracellular-signal-regulated kinase (ERK)-activation dependent, and is mediated by AP-1. HMGA1 antisense construct transfected into P+ cells blocked HMGA1 protein expression and inhibited TPA-induced transformation indicating that HMGA1 is required for transformation. HMGA1 is not however sufficient as HMGA1a or HMGA1b overexpression did not confer transformation sensitivity on P- cells. Although HMGA1 expression is ERK dependent, it is not the only ERK-dependent event required for transformation because it does not suffice to rescue ERK-deficient P- cells. Our study shows (a) TAM 67 when it inhibits AP-1 and transformation, targets a relatively small number of genes; (b) HMGA1, a TAM67 target gene, is causally related to transformation and therefore a potentially important target for cancer prevention.

Animals↗

Spliced human immunodeficiency virus type 1 RNA is reverse transcribed into cDNA within infected cells.

Both the full-length and spliced RNA species of HIV-1 possess the necessary cis-acting elements including the primer binding site (PBS), the polypurine tract (PPT), as well as the 5' R and 3' R regions that are needed for their conversion to double-stranded cDNA through reverse transcription. Since measurable amounts of spliced viral RNA molecules can be detected within virus particles, we have examined the potential for reverse transcription of such virion-associated spliced viral RNA upon infection of permissive cells. Analysis of viral cDNA species by PCR and DNA sequencing not only led to the identification of viral DNA molecules that were reverse transcribed from full-length viral RNA, but also DNA molecules that displayed the same nucleotide sequences as those found in spliced viral RNA, except that the former harbored the complete long terminal repeats (LTR), a feature that distinguishes proviral DNA from viral genomic RNA. Further studies revealed various types of cDNA species that resemble the spliced viral RNA encoding each of the env, tat, rev, or nef genes, of which the nef cDNA represents the majority. Therefore, spliced HIV-1 RNA molecules must have been reverse transcribed along with full-length viral RNA during infection.

Animals↗

Important role for the CA-NC spacer region in the assembly of bovine immunodeficiency virus Gag protein.

Lentiviral Gag proteins contain a short spacer sequence that separates the capsid (CA) from the downstream nucleocapsid (NC) domain. This short spacer has been shown to play an important role in the assembly of human immunodeficiency virus type 1 (HIV-1). We have now extended this finding to the CA-NC spacer motif within the Gag protein of bovine immunodeficiency virus (BIV). Mutation of this latter spacer sequence led to dramatic reductions in virus production, which was mainly attributed to the severely disrupted association of the mutated Gag with the plasma membrane, as shown by the results of membrane flotation assays and confocal microscopy. Detailed mutagenesis analysis of the BIV CA-NC spacer region for virus assembly determinants led to the identification of two key residues, L368 and M372, which are separated by three amino acids, 369-VAA-371. Incidentally, the same two residues are present within the HIV-1 CA-NC spacer region at positions 364 and 368 and have also been shown to be crucial for HIV-1 assembly. Regardless of this conservation between these two viruses, the BIV CA-NC spacer could not be replaced by its HIV-1 counterpart without decreasing virus production, as opposed to its successful replacement by the CA-NC spacer sequences from the nonprimate lentiviruses such as feline immunodeficiency virus (FIV), equine infectious anemia virus and visna virus, with the sequence from FIV showing the highest effectiveness in this regard. Taken together, these data suggest a pivotal role for the CA-NC spacer region in the assembly of BIV Gag; however, the mechanism involved therein may differ from that for the HIV-1 CA-NC spacer.

Amino Acid Motifs↗

[Recombinant human BMP-2 accelerates bone formation of mandibular distraction osteogenesis in rabbits].

OBJECTIVE: To study the effects of rhBMP-2 on bone formation of mandibular distraction osteogenesis in rabbits. METHODS: Bilateral mandibular osteotomies were performed in 12 mature rabbits. 5 mg rhBMP-2 with the collagen carrier was implanted in the osteotomy site of one side of the mandibles. Only the collagen sponge was placed in the contra-lateral side as control. The mandibles of 8 rabbits were lengthened by 6mm using a custom-made distractor. At 4 weeks after the end of distraction, all animals were killed and the distracted calluses were harvested and processed for histological, scanning electron microscopic, as well as Ca/P ratio analysis. RESULTS: The regenerated bone was found in the distraction gap after mandibular lengthening. The mandibular side treated with rhBMP-2 had greater amounts of new bone formation and earlier mineralization than contra-lateral side (non-rhBMP-2 treated). CONCLUSION: Recombinant human BMP-2 appears to be able to accelerate bone formation of mandibular distraction osteogenesis in rabbits.

Animals↗

Effect of nerve growth factor and Schwann cells on axon regeneration of distracted inferior alveolar nerve following mandibular lengthening.

OBJECTIVE: To study the effect of nerve growth factor (NGF) and Schwann cells on axon regeneration of the inferior alveolar nerve following mandibular lengthening with distraction osteogenesis. METHODS: Unilateral mandibular osteodistraction was performed in 9 healthy adult male goats with a distraction rate of 1 mm/d. Every 3 goats were killed on days 7, 14 and 28 after mandibular lengthening, respectively. The inferior alveolar nerves in the distraction callus were harvested and processed for ultrastructural and NGF immunohistochemical study. The inferior alveolar nerves from the contralateral side were used as controls. RESULTS: On day 7 after distraction, axon degeneration and Schwann cell proliferation were observed, and very strong staining of NGF in the distracted nerve was detected. On day 14 after distraction, axon regeneration and remyelination were easily observed, and NGF expression started to decline. On day 28 after distraction, the gray scale of NGF immunoreactivity recovered to the normal value and the Schwann cells almost recovered to their normal state. CONCLUSIONS: Gradual mandibular osteodistraction can result in mild or moderate axon degeneration of the inferior alveolar nerve. Nerve trauma may stimulate the proliferation of Schwann cells and promote the synthesis and secretion of NGF in the Schwann cells. Schwann cells and NGF might play important roles in axon regeneration of the injured inferior alveolar nerve following mandibular lengthening.

Animals↗

[Typing human papilloma virus (HPV) infection in the warts of oral mucosa from HIV-positive patients].

OBJECTIVE: To detect and type human papilloma virus (HPV) in the warts of oral mucosa from HIV-positive patients, and better understand the biological characters of these oral warts. METHODS: Polymerase chain reaction (PCR) was used to detect and type HPV infection by consensus HPV primers Gp5+/Gp6+ and specific HPV primers (HPV6/11, 16, 18, 31, 33) in 34 cases of oral mucosa warts from HIV-positive patients. RESULTS: The HPV infection rate was 88.2% by consensus HPV primers Gp5+/Gp6+; the HPV infection rate of HPV6/11, 16, 18, 31 was respectively 47.06%, 11.67%; 2.94%, and 5.88% by specific HPV primers. CONCLUSION: Most lesions of oral warts from HIV-positive patients are associated with the infection of HPV. The low risk HPV6/11 infection is more common than the high risk HPV16, 18, 31.

HIV Infections↗