Biomedical subjects

Ning Zhang

Publications and source records attributed to Ning Zhang.

At least 73 records · Page 4Linked to original sources

PubMed2005

Structure, expression, and transcriptional regulation of the Strongylocentrotus franciscanus spec gene family encoding intracellular calcium-binding proteins.

The mechanisms by which gene expression patterns emerge during evolution are poorly understood. The sea urchin spec genes offer a useful means to investigate evolutionary mechanisms. Genes of the spec family from Strongylocentrotus purpuratus and Lytechinus pictus have identical patterns of aboral ectoderm-specific expression but exhibit species-specific differences in copy number, genomic structure, temporal expression, and cis-regulatory architecture. Here, we identify spec genes from a phylogenetic intermediate, Strongylocentrotus franciscanus, to gain insight into the evolution of the spec gene family and its transcriptional regulation. We identified two spec genes in the S. franciscanus genome, sfspec1a and sfspec1b, that were orthologous to spec1 from S. purpuratus. sfspec1b transcripts began to accumulate at the blastula stage and became progressively more abundant; this was reminiscent of spec expression in L. pictus but different from that in S. purpuratus. As expected, sfspec1b expression was restricted to aboral ectoderm cells. The six-exon structure of the sfspec1b genomic locus was identical to that of the S. purpuratus spec genes and was bounded by two repeat-spacer-repeat (RSR) repetitive sequence elements, which are conserved features of S. purpuratus spec genes and function as transcriptional enhancers. The enhancer activity of the sfspec1b RSRs was comparable to that of their S. purpuratus counterparts, although the placement and orientation of crucial cis-regulatory elements within the RSRs differed. We discovered a spec gene in S. franciscanus that was only distantly related to other spec genes but was highly conserved in S. purpuratus. Unexpectedly, this gene was expressed exclusively in endoderm lineages. Our results show that the evolution of spec cis-regulatory elements is highly dynamic and that substantial alterations can occur when maintaining or grossly modifying gene expression patterns.

Amino Acid Sequence↗

PubMed2005

Recognition of single nucleotide polymorphisms using scanning potential hairpin denaturation.

Conventional single nucleotide polymorphism (SNP) assays, which based their detection on the stringency or temperature of the washing buffers, have encountered difficulties to distinguish a single base pair mismatch from a perfect match. In this study, scanning potential hairpin denaturation (SPHD) has been developed to detect SNP in a sensitive and reliable manner. Combined with hairpin oligonucleotide probes, scanning surface electric potential was used to induce a dissociation of double-stranded DNA around a unique "melting potential" (Vm), and it generated a high-contrast SNP recognition signal. A 21 base pair p53 gene segment was used to test this novel method. A single nucleotide mismatch to the hairpin probes caused an average of 400-800 mV difference in melting potential against the perfect match, while the error of this assay was lower than 20 mV. Experiments demonstrated that the hairpin stem was critical to the method. The concept of scanning potential hairpin denaturation could also be used extensively in different areas of nucleotide hybridization based assays.

DNA↗

PubMed2005

Strongylocentrotus purpuratus transcription factor GATA-E binds to and represses transcription at an Otx-Goosecoid cis-regulatory element within the aboral ectoderm-specific spec2a enhancer.

During Strongylocentrotus purpuratus embryogenesis, aboral ectoderm-specific expression of spec2a relies on an upstream enhancer that confers its spatial specificity largely through repression. The purpose of this study was to determine how spec2a expression is repressed in endoderm and oral ectoderm territories. A 78-base pair DNA sequence within the enhancer contains five tightly spaced cis-regulatory elements including proximal (TAATCT) and distal (TAATCC) elements that bind to both SpOtx, a broadly distributed transcriptional activator, and SpGoosecoid (SpGsc), an oral ectoderm-restricted transcriptional repressor. We show here that these two seemingly redundant Otx/Gsc elements have distinct functions. The proximal element bound to SpGATA-E, an endomesoderm-specific transcription factor. Treatment with SpGATA-E and SpGsc morpholino antisense oligonucleotides (MASOs) resulted in enhanced transcriptional activity from the proximal element, suggesting that both factors functioned as repressors at this site. SpGATA-E MASO-treated embryos failed to express ectoderm markers, indicating a role for SpGATA-E in ectoderm differentiation. The spec2a proximal element was distinct from the corresponding element in the related spec1 enhancer, and swaps between spec1 and spec2a cis-regulatory elements indicated, that for optimal repression, the proximal element had to interact with a nearby CCAAT-binding factor element. Our results show that the recently evolved proximal element contributes to the repression of spec2a in endomesoderm and oral ectoderm territories.

Amino Acid Sequence↗

PubMed2005

NF-kappaB and not the MAPK signaling pathway regulates GADD45beta expression during acute inflammation.

The GADD45 (growth arrest and DNA damage-inducible) family of genes is involved in the regulation of cell cycle progression and apoptosis. To study signaling pathways affecting GADD45beta expression and to examine systematically in vivo the GADD45beta expression in tissues following various toxic stresses, we created a transgenic mouse by fusing the GADD45beta promoter to firefly luciferase (Gadd45beta-luc). In vivo GADD45beta expression was assessed by measuring the luciferase activity in the Gadd45beta-luc transgenic mouse using a non-invasive imaging system (IVIS Imaging System, Xenogen Corporation). We found that a number of agents that induce oxidative stress, such as sodium arsenite, CCl4, lipopolysaccharide (LPS), or tumor necrosis factor-alpha, are able to induce luciferase expression throughout the entire animal. In liver, spleen, lung, intestine, kidney, and heart, we observed an induction of luciferase activity after LPS treatment, which correlates with an increase of GADD45beta mRNA in these tissues. Processes that induce DNA damage activate the NF-kappaB signaling pathway. Several inhibitors of the NF-kappaB signaling pathway, including dexamethasone, thalidomide, and a proteasome inhibitor, bortezomib, showed inhibitory effects on LPS-induced GADD45beta expression as indicated by a decrease of the luciferase activity. Northern blot analysis confirmed a broad inhibitory effect of bortezomib on LPS-induced GADD45beta mRNA expression in spleen, lung, and intestine. In liver of bortezomib-treated mice, we observed a reverse correlation between the luciferase activity and the GADD45beta mRNA level. We speculate that such a discrepancy could be due to severe liver toxicity caused by bortezomib and LPS co-treatment. MAPK inhibitors had transient and inconsistent effects on LPS-induced luciferase expression. Our data are consistent with the notion that NF-kappaB, but not the MAPK signaling pathways, is involved in the in vivo regulation of GADD45beta expression. Thus, NF-kappaB signaling involves induction of GADD45beta expression, which supports the proposed role of GADD45beta in protecting cells against DNA damaged under various stress conditions.

Animals↗

PubMed2005

[The expression of hypoxia inducible factor-1,2 alpha in sporadic clear cell renal cell carcinoma and their relationships to the mutations of von Hippel-Lindau gene].

OBJECTIVE: To evaluate the expression of hypoxia inducible factor (HIF)-1alpha, 2alpha in sporadic clear cell renal cell carcinoma and their relationships to the mutations of von Hippel-Lindau (VHL) gene. METHODS: Mutations of VHL gene, expression of HIF-1alpha and 2alpha were detected by polymerase chain reaction (PCR), direct DNA sequencing and immunohistochemistry in 77 cases of Chinese sporadic clear cell renal cell carcinoma (CCRCC). The stage was pT(1)N(0)M(0)in 55 patients (71%), pT(2)N(0)M(0) in 7 patients (9%), pT(3)N(0)M(0) in 14 patients (18%), and pT(4)N(0)M(0) in 1 patient (1%). The classification according to the tumor nuclear grading system showed 15 carcinomas (19%) of tumor nuclear grade 1, 56 (73%) of tumor nuclear grade 2 and 6 (8%) of tumor nuclear grade 3. RESULTS: None of the VHL gene mutations were found in all the normal tissue specimens. VHL gene mutations were detected in 40 (52%) cases of CCRCC. The positive rate of HIF-2alpha (81%) was higher than that of HIF-1alpha (66%) (chi(2) = 23.310, P < 0.01); The positive rate of HIF-1alpha and HIF-2alpha in the cases of mutations (98% and 93% respectively) was higher than that of them in non-mutations (32% and 68% respectively) (chi(2) = 36.386, 7.617, P < 0.01); The correlation between HIF-1alpha and VHL gene mutations was closer than that between HIF-2alpha and VHL gene mutations (partial correlation coefficiency was 4.481 and 2.027 respectively, P < 0.01). The expression of HIF-1alpha and 2alpha in different pathological grade and stage of CCRCC showed no significant difference (P > 0.05). CONCLUSIONS: Our study suggests that VHL gene mutations are frequent in sporadic CCRCC, and the high expression of HIF-1alpha and 2alpha are found in the group of VHL mutations. However, we have not found significant correlation between the expression of HIF-1alpha and 2alpha and pathological grade and stage of CCRCC in our study.

Adult↗

PubMed2005

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1.

Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca(2+) influx mediated by TRPV1. When CCR1:TRPV1/HEK293 cells were pretreated with CCL3, the sensitivity of TRPV1, as indicated by the Ca(2+) influx, was increased approximately 3-fold. RT-PCR analysis showed that a spectrum of chemokine and cytokine receptors is expressed in rat dorsal root ganglia (DRG). Immunohistochemical staining of DRG showed that CCR1 is coexpressed with TRPV1 in >85% of small-diameter neurons. CCR1 on DRG neurons was functional, as demonstrated by CCL3-induced Ca(2+) ion influx and PKC activation. Pretreatment with CCL3 enhanced the response of DRG neurons to capsaicin or anandamide. This sensitization was inhibited by pertussis toxin, U73122, or chelerythrine chloride, inhibitors of Gi-protein, phospholipase C, and protein kinase C, respectively. Intraplantar injection of mice with CCL3 decreased their hot-plate response latency. That a proinflammatory chemokine, by interacting with its receptor on small-diameter neurons, sensitizes TRPV1 reveals a previously undescribed mechanism of receptor cross-sensitization that may contribute to hyperalgesia during inflammation.

Animals↗

PubMed2005

Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells.

Chemotaxis plays an important role in cancer cell metastasis. In this study, we showed that epidermal growth factor (EGF) was a more potent chemoattractant than chemokine SDF-1alpha/CXCL12 for human breast cancer cell MDA-MB-231. Different inhibitors were used to evaluate the involvement of 12 protein kinase C (PKC) isotypes in the chemotactic signaling pathway. Chelerythrine chloride, an inhibitor of all PKC isotypes, blocked chemotaxis, whereas inhibitors of classic and novel PKC, such as Gö6976, Gö6850, or calphostin C, only impaired EGF-induced chemotaxis to a minor extent by not greater-than32% inhibition. These data suggested that atypical PKC were involved. The ligand-induced actin polymerization and cell adhesion were also similarly dependent on atypical PKC. Immunofluorescent staining showed an EGF-induced, LY294002-sensitive translocation of PKCzeta from the cytosol to the plasma membrane, indicating that EGF was capable of activating PKCzeta, probably via phosphoinositide 3 kinases. A myristoylated PKCzeta pseudosubstrate blocked the chemotaxis with an IC(50) of 20 mumol/L. To expand our investigation, we further showed that in MCF-7 and T47D, two additional human breast cancer cell lines, EGF-activated PKCzeta and the PKCzeta pseudosubstrate, inhibited chemotaxis. Taken together, our data suggest that PKCzeta is an essential component of the EGF-stimulated chemotactic signaling pathway in human breast cancer cells.

Alkaloids↗

PubMed2005

The tumor-specific hyperactive forms of cyclin E are resistant to inhibition by p21 and p27.

The low molecular weight (LMW) isoforms of cyclin E are unique to cancer cells. In breast cancer, such alteration of cyclin E is a very strong predictor of poor patient outcome. Here we show that alteration in binding properties of these LMW isoforms to CDK2 and the CDK inhibitors (CKIs), p21 and p27, results in their functional hyperactivity. The LMW forms of cyclin E are severalfold more effective at binding to CDK2. Additionally, compared with the full-length cyclin E-CDK2 complexes, the LMW cyclin E-CDK2 complexes are significantly more resistant to inhibition by p21 and p27, despite equal binding of the CKIs to the LMW complexes. When both the full-length and the LMW cyclin E are co-expressed, p27 preferentially binds to the LMW forms yet is unable to inhibit the CDK2 activity. Thus, the LMW forms of cyclin E may contribute to tumorigenesis through their resistance to the inhibitory activities of p21 and p27 while sequestering these CKIs from the full-length cyclin E.

Animals↗

PubMed2005

[Analysis of biallelic inactivation of the von Hippel-Lindau tumor suppressor gene VHL in patients of renal cell carcinoma patient].

OBJECTIVE: To investigate biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) in patient of renal cell carcinoma (RCC) patient. METHODS: We extracted tumor and normal DNA from 41 RCC patients. Mutation of VHL gene from tumor tissue was detected from tumor tissue by polymerase chain reaction (PCR) and direct sequencing. Two single nucleotide polymorphism (SNP) sites located in VHL gene were analyzed by PCR restriction fragment length polymorphism, and loss of heterozygosity (LOH) was analyzed for VHL gene by comparing between tumor with normal tissue. RESULTS: Mutation and LOH of VHL gene was found in 51% (21/41) and 42% (8/19) of RCC patients respectively. LOH was highly associated with mutation positive tumors (r = 0.78) and VHL biallelic inactivation was detected in 37% of RCC patients. CONCLUSION: Biallelic inactivation of VHL gene occurs in RCC due to VHL mutation and LOH, and its frequency rate is 37%.

Adult↗

PubMed2005

Tissue-engineering approaches for axonal guidance.

Owing to the profound impact of nervous system damage, extensive studies have been carried out aimed at facilitating axonal regeneration following injury. Tissue engineering, as an emerging and rapidly growing field, has received extensive attention for nervous system axonal guidance. Numerous engineered substrates containing oriented extracellular matrix molecules, cells or channels have displayed potential of supporting axonal regeneration and functional recovery. Most attempts are focused on seeking new biomaterials, new cell sources, as well as novel designs of tissue-engineered neuronal bridging devices, to generate safer and more efficacious neuronal tissue repairs.

Animals↗

PubMed2005

High throughput proteome screening for biomarker detection.

Mass spectrometry-based quantitative proteomics has become an important component of biological and clinical research. Current methods, while highly developed and powerful, are falling short of their goal of routinely analyzing whole proteomes mainly because the wealth of proteomic information accumulated from prior studies is not used for the planning or interpretation of present experiments. The consequence of this situation is that in every proteomic experiment the proteome is rediscovered. In this report we describe an approach for quantitative proteomics that builds on the extensive prior knowledge of proteomes and a platform for the implementation of the method. The method is based on the selection and chemical synthesis of isotopically labeled reference peptides that uniquely identify a particular protein and the addition of a panel of such peptides to the sample mixture consisting of tryptic peptides from the proteome in question. The platform consists of a peptide separation module for the generation of ordered peptide arrays from the combined peptide sample on the sample plate of a MALDI mass spectrometer, a high throughput MALDI-TOF/TOF mass spectrometer, and a suite of software tools for the selective analysis of the targeted peptides and the interpretation of the results. Applying the method to the analysis of the human blood serum proteome we demonstrate the feasibility of using mass spectrometry-based proteomics as a high throughput screening technology for the detection and quantification of targeted proteins in a complex system.

Automation↗

PubMed2005

ProbIDtree: an automated software program capable of identifying multiple peptides from a single collision-induced dissociation spectrum collected by a tandem mass spectrometer.

In MS/MS experiments with automated precursor ion, selection only a fraction of sequencing attempts lead to the successful identification of a peptide. A number of reasons may contribute to this situation. They include poor fragmentation of the selected precursor ion, the presence of modified residues in the peptide, mismatches with sequence databases, and frequently, the concurrent fragmentation of multiple precursors in the same CID attempt. Current database search engines are incapable of correctly assigning the sequences of multiple precursors to such spectra. We have developed a search engine, ProbIDtree, which can identify multiple peptides from a CID spectrum generated by the concurrent fragmentation of multiple precursor ions. This is achieved by iterative database searching in which the submitted spectra are generated by subtracting the fragment ions assigned to a tentatively matched peptide from the acquired spectrum and in which each match is assigned a tentative probability score. Tentatively matched peptides are organized in a tree structure from which their adjusted probability scores are calculated and used to determine the correct identifications. The results using MALDI-TOF-TOF MS/MS data demonstrate that multiple peptides can be effectively identified simultaneously with high confidence using ProbIDtree.

Algorithms↗

PubMed2005

Expression of heat stress protein 70 mRNA in patients with chronic obstructive pulmonary disease and its significance.

The effects of cigarette smoke extract (CSE) on the expression of heat stress protein 70 (Hsp70) in human bronchi smooth muscle cells were investigated in vitro, and the changes in Hsp70 mRNA in the patients with chronic obstructive pulmonary disease and their significance were explored. Human bronchi smooth muscle cells were cultured with CSE at the different concentrations. The expression of Hsp70 mRNA and Hsp70 was detected by reverse translation-polymerase chain reaction (RT-PCR) and Western blotting respectively. Levels of Hsp70 mRNA and Hsp70 in lymphocytes from 20 patients with COPD and 20 healthy smoking control subjects were measured by RT-PCR and Western blotting. The results showed the expression of both Hsp70 mRNA and Hsp70 was decreased conformably in human bronchi smooth muscle cells treated with CSE at certain concentration in vitro. The A values of the Hsp70 mRNA expression were 0.24 +/- 0.11 and 0. 42 +/- 0.13 respectively in COPD patients and healthy smoking controls with the difference being significant (P < 0.01). There was also significant difference in the A values of the Hsp70 expression between COPD patients and healthy smoking controls (20.9 +/- 9.9 vs 44.8 +/- 15.3, P < 0.01). The levels of Hsp70 mRNA had strongly positive correlation with Hsp70 protein (r = 0.85, P < 0.01). It was suggested that the expression of Hsp70 mRNA was in concordance with the expression of Hsp70, which could provide a basis on the study of Hsp70 gene regulation and Hsp70 gene in the development of COPD.

Bronchi↗

PubMed2005

Cooling to 10 degrees C and treatment with Cyclosporine A improve cerebral recovery following prolonged hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: This study was undertaken to assess whether cooling to 10 degrees C and/or treatment with Cyclosporine A (CsA) can reduce neurological injury during prolonged hypothermic circulatory arrest (HCA) in a chronic animal model. METHODS: In this blinded study, 24 pigs (20-23 kg) were randomized to HCA for 90 min at 20 degrees C (n=8), at 10 degrees C (n=8), or at 10 degrees C with 5 mg/kg CsA (n=8). CsA (or placebo) were given intravenously before and for 3 days after HCA. Hemodynamics and neurophysiological data were monitored periodically throughout the experiment and for 3 h after HCA, as well as intracranial pressure (ICP), which has been shown to correlate with outcome. Daily neurological/behavioral evaluation (mental status, coordination and appetite; 12=normal and 0=coma or death) was carried out until sacrifice on postoperative day (POD) 3. RESULTS: Overall survival rate was 83.3%: one 20 degrees C control, two 10 degrees C controls, and one 10 degrees C/CsA pig died and were replaced. Basic hemodynamic data revealed no significant differences between groups. ICP differed significantly among the groups during the first 3 h postoperatively (P=0.003 by repeated measures ANOVA); it was higher in the 20 degrees C group than in the 10 degrees C/CsA or 10 degrees C control groups. Recovery of visual evoked potentials was significantly better in the 10 degrees C/CsA group than in the 10 degrees C control group; no recovery was seen by 3 h in the 20 degrees C control group. Postoperative behavioral scores also differed significantly between the groups, P=0.03: a good behavioral outcome--a score >9 on POD3--was more prevalent among CsA-treated pigs (75%) than among 10 degrees C controls (50%), or 20 degrees C controls (12.5%, P=0.06). CONCLUSIONS: The data suggest that cooling to 10 degrees C and CsA treatment are both of benefit in improving cerebral recovery after HCA when compared with untreated 20 degrees C controls, and may be synergistic.

Animals↗

PubMed2005

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.

Animals↗

PubMed2005

Optimal temperature for selective cerebral perfusion.

OBJECTIVE: Although combinations of hypothermic circulatory arrest and antegrade selective cerebral perfusion are used for cerebral protection during arch surgery, there is no consensus regarding the optimal temperature during selective cerebral perfusion. This study explored the effect of different temperatures during selective cerebral perfusion on cerebral metabolism and neurologic outcome. METHODS: In this blinded study, 40 pigs (19-21 kg) were randomized into 4 groups after 30 minutes of hypothermic circulatory arrest at 20 degrees C. During a 60-minute interval of selective cerebral perfusion, with flow regulated to maintain a perfusion pressure of 50 mm Hg, pigs were perfused at 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C. Fluorescent microspheres enabled calculation of cerebral blood flow during perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular resistance, and oxygen consumption were also monitored. Behavioral scores were obtained for 7 days after surgery. RESULTS: Cerebral blood flow decreased significantly ( P < .002) during cooling in all groups: it was significantly higher throughout selective cerebral perfusion in the 20 degrees C to 25 degrees C versus the 10 degrees C to 15 degrees C group ( P = .0001) and remained higher during recovery ( P = .0001). Oxygen consumption decreased significantly with cooling ( P = .0001), remained low during perfusion, and rebounded with rewarming but was significantly lower at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C throughout selective cerebral perfusion ( P = .003) and after CPB was discontinued ( P = .001). Postoperative behavioral scores were significantly better after selective cerebral perfusion at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C ( P = .001). CONCLUSIONS: This study suggests that selective cerebral perfusion at 10 degrees C to 15 degrees C provides better cerebral protection than selective cerebral perfusion at 20 degrees C to 25 degrees C, even though oxygen consumption remains low for hours after selective cerebral perfusion at 10 degrees C to 15 degrees C. Prompt return of metabolism to baseline levels after hypothermic circulatory arrest/selective cerebral perfusion does not necessarily predict superior behavioral outcome.

Animals↗

PubMed2005

On multirate optimality of JPEG2000 code stream.

Arguably, the most important and defining feature of the JPEG2000 image compression standard is its R-D optimized code stream of multiple progressive layers. This code stream is an interleaving of many scalable code streams of different sample blocks. In this paper, we reexamine the R-D optimality of JPEG2000 scalable code streams under an expected multirate distortion measure (EMRD), which is defined to be the average distortion weighted by a probability distribution of operational rates in a given range, rather than for one or few fixed rates. We prove that the JPEG2000 code stream constructed by embedded block coding of optimal truncation is almost optimal in the EMRD sense for uniform rate distribution function, even if the individual scalable code streams have nonconvex operational R-D curves. We also develop algorithms to optimize the JPEG2000 code stream for exponential and Laplacian rate distribution functions while maintaining compatibility with the JPEG2000 standard. Both of our analytical and experimental results lend strong support to JPEG2000 as a near-optimal scalable image codec in a fairly general setting.

Algorithms↗

PubMed2005

Target-specific catecholamine elevation induced by anticonvulsant thalamic deep brain stimulation.

PURPOSE: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective in raising EEG and clonic seizure threshold in experimental models. Little is known about the specific properties of DBS that afford its anticonvulsant effect. We sought to test the hypothesis that experimental seizures and the anticonvulsant action of AN DBS alter the underlying regional neurochemistry of AN, specifically with facilitation of the serotonergic system to local electrical stimulation. METHODS: Halothane-anesthetized adult Sprague-Dawley male rats underwent stereotactically guided bilateral placement of bipolar stimulating steel electrodes and dialysis probes-guide cannulae in AN and posterior thalamus (PT), and placement of four epidural EEG screw electrodes 48 h before experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n=7 per group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min). Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples were collected from AN and PT in 20-min epochs. AN stimulation was delivered (150 microA; 0.1-ms pulse duration) 40 min before and continued during PTZ infusion. RESULTS: Bilateral AN stimulation delayed the onset of EEG seizures compared with controls: 82+/-8 vs. 58+/-5 min (p=0.02). PTZ infusion alone, or together with stimulation, resulted in a steady increase in norepinephrine (NE), but not dopamine, at AN and PT sites (p<0.001). Although extracellular serotonin was measured at very low levels, the metabolite, 5-hydroxyindoleacetic acid (5-HIAA) increased selectively in AN after stimulation and during preconvulsant infusion of PTZ (p<0.001), returning to baseline after the first generalized seizure. CONCLUSIONS: These data suggest that PTZ and DBS together enhance the nonselective release of NE in thalamic nuclei while specifically stimulating AN-localized serotonin. Low serotonin levels at baseline and during STIM alone or PTZ infusion may indicate efficient reuptake systems for serotonin, with 5-HIAA serving as a surrogate marker for serotonergic activity. Modulation of the AN-specific serotonergic activity may be critical in altering PTZ seizure threshold and be an important neurotransmitter system underlying the efficacy of AN DBS.

Animals↗