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Biomedical subjects

C Zhou

Publications and source records attributed to C Zhou.

At least 19 recordsLinked to original sources

Multilocation trial of ceftiofur for treatment of postpartum cows with fever.

OBJECTIVE: To evaluate the effect of ceftiofur for treatment of postpartum cows with fever. DESIGN: Multilocation randomized complete block design trial. ANIMALS: 330 cows. PROCEDURE: Cows with rectal temperature > or = 39.5 C (103.1 F) during the first 10 postpartum days were randomly assigned to a treatment (ceftiofur; 1 mg/kg [0.45 mg/lb] of body weight daily for 3 days) or untreated control group. Cure (no additional or alternative antimicrobial treatment used, rectal temperature < 39.5 C, and no other concurrent clinical signs of disease when evaluated at 9 or 10 days after enrollment), milk production, and rectal temperature were evaluated. RESULTS: Ceftiofur-treated cows were significantly more likely to be cured than control cows (56.0 vs 28.9%, respectively), with an odds ratio of 3.14 when vaginal discharge (a factor with moderate interaction with treatment) was present at enrollment. Among cows that had an abnormal calving (a significant interaction factor), treated cows had first milking yield 2.27 kg (5 lb) greater than control cows. Treated cows had a significantly greater reduction in rectal temperature (1.19 C [2.14 Fl), compared with control cows (1.04 C [1.87 F]). CONCLUSIONS AND CLINICAL RELEVANCE: Parenteral administration of ceftiofur significantly improved cure rate, milk yield, and rectal temperature in postpartum cows with fever and vaginal discharge or dystocia. These findings provide information to determine appropriate treatment for postpartum cows, which for years has been debated in the dairy industry.

Animals↗

COUP-TFI: an intrinsic factor for early regionalization of the neocortex.

Regionalization of the cerebral cortex is thought to involve two phases: an early regionalization phase and a later refinement phase. It has been shown that early regionalization of the neocortex does not require thalamic inputs and is regulated by intrinsic factors. Recently, two such intrinsic factors, Pax6 and Emx2, have been identified. In this study, we identified COUP-TFI as a regulatory factor for early neocortical regionalization. The spatial and temporal expression pattern of COUP-TFI suggested a role in specification of the neocortex and in maintaining cortical identity. Altered region-specific expression of marker genes in the cortex as well as miswired area-specific connections between the cortex and the thalamus in COUP-TFI null mice indicate COUP-TFI plays a critical role in regulating early regionalization. Our results substantiate that COUP-TFI, an intrinsic factor, may work in concert with Pax6 and Emx2 to specify neocortical identity.

Animals↗

Array-enhanced coherence resonance: nontrivial effects of heterogeneity and spatial independence of noise.

We demonstrate the effect of coherence resonance in a heterogeneous array of coupled Fitz Hugh-Nagumo neurons. It is shown that coupling of such elements leads to a significantly stronger coherence compared to that of a single element. We report nontrivial effects of parameter heterogeneity and spatial independence of noise on array-enhanced coherence resonance; especially, we find that (i) the coherence increases as spatial correlation of the noise decreases, and (ii) inhomogeneity in the parameters of the array enhances the coherence. Our results have the implication that generic heterogeneity and background noise can play a constructive role to enhance the time precision of firing in neural systems.

Journal Article↗

Synthesis and anticancer activity of novel chiral D-glucose derived bis-imidazoles and their analogs.

A series of novel D-glucose derived bis-imidazoles and their analogs, which possess potential in bioorganic and supramolecular chemistry, were designed and synthesized from methyl alpha-D-glucoside through protection, bis-bromination, N-alkylation and deprotection. All new compounds were characterized by HRMS, 1H, 13C and DEPT NMR spectroscopy as well as elemental analysis. The 1H-(1)H and 1H-(13)C 2D NMR spectra for some compounds were also recorded. Some regular features of 13C and 1H NMR spectra were summarized. The anticancer activity of some compounds was evaluated.

Antineoplastic Agents↗

The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p.

BACKGROUND: The function of the fission yeast cullins Pcu1p and Pcu4p requires modification by the ubiquitin-related peptide Ned8p. A recent report by Lyapina et al. shows that the COP9/signalosome (CSN), a multifunctional eight subunit complex, regulates Ned8p modification of Pcu1p. Disruption of caa1/csn1, which encodes subunit 1 of the putative S. pombe CSN, results in accumulation of Pcu1p exclusively in the modified form. However, it remained unclear whether this reflects global control of all cullins by the entire CSN complex. RESULTS: We demonstrate that multiple CSN subunits control Ned8p modification of Pcu3p, another fission yeast cullin, which, in complex with the RING domain protein Pip1p, forms a ubiquitin ligase that functions in cellular stress response. Pcu3p is modified by Ned8p on Lys 729 and accumulates exclusively in the neddylated form in cells lacking the CSN subunits 1, 3, 4, and 5. These CSN subunits co-elute with Pcu3p in gel filtration fractions corresponding to approximately 550 kDa and specifically bind both native and Ned8p-modified Pcu3p in vivo. While CSN does not influence the subcellular localization of Pcu3p, Pcu3p-associated in vitro ubiquitin ligase activity is stimulated in the absence of CSN. CONCLUSIONS: Taken together, our data suggest that CSN is a global regulator of Ned8p modification of multiple cullins and potentially other proteins involved in cellular regulation.

COP9 Signalosome Complex↗

Identification of differentially expressed genes in the denervated rat hippocampus by cDNA arrays.

To elucidate the molecular mechanism underlying the physiological responses to injury in the central nervous system, gene expression profiles in rodent hippocampus following perforant path transection were investigated using cDNA array hybridization. Of the 8000 arrayed clones, 47 exhibited differential expression by >3-fold difference in the denervated hippocampus from control, with 15 up-regulated and 22 down-regulated. They can be functionally assigned into several classes, among which the most prominent are those coding proteins involved in macromolecules synthesis and processing. Northern blot analysis verified the validation of the aforementioned array data. These results throw some new light on the physiological responses of the hippocampus to entorhinal deafferentation at molecular level.

Acetylcholinesterase↗

Structure of the human M(2) muscarinic acetylcholine receptor gene and its promoter.

The M(2) muscarinic receptor inhibits the release of acetylcholine from cholinergic fibers in the lungs and elsewhere. In airway parasympathetic neurons, M(2) receptor expression is decreased by viral infections and by interferon-gamma, increasing actylcholine release. Dexamethasone increases M(2) receptor expression, decreasing acetylcholine release. We carried out 5' rapid amplification of cDNA ends beginning with mRNA from human heart and IMR32 human neuroblastoma cells. This demonstrated a 5' UTR of 100 BP, corresponding to two sequences on chromosome 7, separated by a 22.6 kB intron. The splice acceptor site is at -45 relative to the initiating atg. The 3000 BP upstream of 5' RACE product were subcloned into a pGL3 luciferase reporter vector. Deletional constructs were expressed in IMR32 cells. These demonstrated that 412 BP provided full expression of the reporter gene, and suggested a repressor element between -1848 and -1510.

Base Sequence↗

Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.

3T3 Cells↗

Gene expression profile changes in initiation and progression of squamous cell carcinoma of esophagus.

Tumorigenesis is a complex process involving multiple genes. As a step toward understanding the complicated changes between normal and malignant cells, this report focused on gene expression profile variations among normal and abnormal esophageal epithelium tissues. The cDNA microarray approach was used to investigate gene expression profiles of 5 different stages during initiation and progression of esophageal cancer. According to pathological characteristics, these 5 stages were normal, dysplasia I (mild dysplasia), dysplasia II (moderate dysplasia), carcinoma in situ (CIS) and squamous cell carcinoma of esophagus (SCC). Comparing and analyzing those gene expression profiles, we observed that the expression levels of many genes changed in dysplasia I and some known tumor-related genes were over-expressed or under-expressed in all 4 abnormal stages. Using principle component analysis we identified a set of genes that may play an important role in tumor development. Hybridization data were confirmed by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. These results suggest that cDNA microarray technology is a useful tool to discover genes frequently involved in esophageal neoplasia and provides novel clues to diagnosis, early detection and intervention of SCC.

Carcinoma in Situ↗

Atp-binding cassette transporter ABC2/ABCA2 in the rat brain: a novel mammalian lysosome-associated membrane protein and a specific marker for oligodendrocytes but not for myelin sheaths.

We recently cloned a full-length cDNA of the rat ATP-binding cassette transporter 2 (ABC2, or ABCA2) protein, a member of the ABC1 (or ABCA) subfamily (-ABC1/ABCA1 is a causal gene for Tangier disease) and found it to be strongly expressed in the rat brain. In this study, we identified ABC2 as a lysosome-associated membrane protein that is being localized specifically in oligodendrocytes. The ABC2-immunolabeled cells were detected mainly in the white matter but were also scattered in gray matter throughout the whole brain. In addition, these cells were found to be colocalized with 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) immunoreactivity when the marker antibody for oligodendrocytes was used. However, no such colocalization was observed with markers for other kinds of glial cells. Unlike the CNP antibody, which also intensely stains myelin sheaths in the white matter, ABC2 immunoreactivity was detected only in the cell bodies of oligodendrocytes. At the ultrastructural level, ABC2 immunoreactivity was detected mostly around lysosome and partly in Golgi apparatus by electron microscopy. This was confirmed by immunocolocalization of ABC2 and lysosomal markers in a neuroblastoma cell line. Immunoblotting analysis of ABC2 from the whole brain and the ABC2-transfected cell line revealed bands at approximately 260 kDa. The result of in situ hybridization with a riboprobe for ABC2 matched the results obtained from immunostaining. These findings strongly suggest that ABC2 is a specific marker for oligodendrocytes but not for myelinsheaths and that it is as a novel mammalian lysosome-associated membrane protein involved in myelinization or other kinds of metabolism in the CNS.

ATP-Binding Cassette Transporters↗

Synchronization regimes in coupled noisy excitable systems.

We study synchronization regimes in a system of two coupled noisy excitable systems which exhibit excitability close to an Andronov bifurcation. The uncoupled system possesses three fixed points: a node, a saddle, and an unstable focus. We demonstrate that with an increase of coupling strength the system undergoes transitions from a desynchronous state to a train synchronization regime to a phase synchronization regime, and then to a complete synchronization regime. Train synchronization is a consequence of the existence of a saddle in the phase space. The mechanism of transitions in coupled noisy excitable systems is different from that in coupled phase-coherent chaotic systems.

Journal Article↗

Preparation and blood compatibility of polysiloxane/liquid-crystal composite membranes.

Polysiloxane/liquid crystal composite membrane was first suggested to be used as biomaterials. In this work, the polydimethyl-methylhydrosiloxane and polydimethyl-methylethylenesilosiane, as a substrate, were blended with cholesteryl oleyl carbonate (COC) in tetrahydrofuran, and then crosslinked into membranes on glass plates by means of the platinum catalyst at 110 degrees C for 20 min. The effects of the liquid-crystal content in composite membranes on the formation of liquid-crystal phase were verified by the observation of optical polarization microscopy. The relationship between the morphology of the composite membranes and blood compatibility was identified by the dynamic blood-clotting tests, haemolysis ratio measurement, platelet adhesion and SEM observation. The results show that the blood-compatibility of composite membranes with the concentration of liquid crystal 20, 30% (wt) is more excellent than that of other composite membranes.

Biocompatible Materials↗

Fine mapping of ovine ceroid lipofuscinosis confirms orthology with CLN6.

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases with severe neurodegenerative pathology. An ovine model (OCL) has well defined parallels with the human disease at a biochemical and pathological level. The gene for OCL is located in the chromosomal region OAR 7q13-15. This region is syntenic with HSA 15q21-23 suggesting that OCL and CLN6 represent mutations in orthologous genes. New microsatellite markers were used for refinement of the OCL critical region. YAC clones that span the critical region have been isolated and comparative gene mapping confirms that the regions for CLN6 and OCL are equivalent.

Animals↗

Branched nanowire based guanine rich oligonucleotides.

Self-assembly and aggregation of guanine rich sequences can provide useful insights into DNA nanotechnology and telomeric structure and function. In this paper, we designed a guanine rich sequence d(GGCGTTTTGCGG). We found that it can form stable structure in appropriate condition and it exhibits an anomalous CD spectra. This structures can be imaged in ambient environment with a Nanoscope III AFM (Digital Instruments). We found it forms branch structure and long multistrand DNA nanowire after incubation at 37 degrees C for 6-12 hours in 25 mM TE (pH=8.0) + 5 mM Mg2+ + 50 mM K+. The ability to self-assemble into branches and long wires not only clearly demonstrate its potential as scaffold structures for nanotechnology, but also give aids to understand telomeric structure further. We have proposed a model to explain how these structures formed.

Circular Dichroism↗

SPO14 separation-of-function mutations define unique roles for phospholipase D in secretion and cellular differentiation in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene, catalyzes the hydrolysis of phosphatidylcholine, producing choline and phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis and is required for Golgi function when the normal secretory apparatus is perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14 that support Sec14-independent secretion but not sporulation. Identification of these separation-of-function alleles indicates that the role of PLD in these two physiological processes is distinct. Analyses of the mutants reveal that the corresponding proteins are stable, phosphorylated, catalytically active in vitro, and can localize properly within the cell during meiosis. Surprisingly, the separation-of-function mutations map to the conserved catalytic region of the PLD protein. Choline and phosphatidic acid molecular species profiles during Sec14-independent secretion and meiosis reveal that while strains harboring one of these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent secretion, they fail to do so during sporulation or normal vegetative growth. These results demonstrate that Spo14 PLD catalytic activity and cellular function can be differentially regulated at the level of phosphatidylcholine hydrolysis.

Alleles↗

Computerized image analysis: estimation of breast density on mammograms.

An automated image analysis tool is being developed for the estimation of mammographic breast density. This tool may be useful for risk estimation or for monitoring breast density change in prevention or intervention programs. In this preliminary study, a data set of 4-view mammograms from 65 patients was used to evaluate our approach. Breast density analysis was performed on the digitized mammograms in three stages. First, the breast region was segmented from the surrounding background by an automated breast boundary-tracking algorithm. Second, an adaptive dynamic range compression technique was applied to the breast image to reduce the range of the gray level distribution in the low frequency background and to enhance the differences in the characteristic features of the gray level histogram for breasts of different densities. Third, rule-based classification was used to classify the breast images into four classes according to the characteristic features of their gray level histogram. For each image, a gray level threshold was automatically determined to segment the dense tissue from the breast region. The area of segmented dense tissue as a percentage of the breast area was then estimated. To evaluate the performance of the algorithm, the computer segmentation results were compared to manual segmentation with interactive thresholding by five radiologists. A "true" percent dense area for each mammogram was obtained by averaging the manually segmented areas of the radiologists. We found that the histograms of 6% (8 CC and 8 MLO views) of the breast regions were misclassified by the computer, resulting in poor segmentation of the dense region. For the images with correct classification, the correlation between the computer-estimated percent dense area and the "truth" was 0.94 and 0.91, respectively, for CC and MLO views, with a mean bias of less than 2%. The mean biases of the five radiologists' visual estimates for the same images ranged from 0.1% to 11%. The results demonstrate the feasibility of estimating mammographic breast density using computer vision techniques and its potential to improve the accuracy and reproducibility of breast density estimation in comparison with the subjective visual assessment by radiologists.

Biophysical Phenomena↗

Point load wave excitation in multi-layered solids: experiments and model verification.

Studies of transient wave propagation in a single plate, a two-layer plate structure, and a two-layer-on-a-half-space structure are reported. Experimental results are used to verify the accuracy of a new model for wave propagation in layered solids. The experiments are performed using point load excitation and point detection at the surface of the layered structure. The basis of the new wave propagation model is first introduced. Then, experiments performed on a single plate are described. Results from different wave sources, plate materials, and wave sensors are compared with each other and with computed results from the model. The transient source function for a pencil-lead-break wave source is obtained. Next, the results of experiments performed on a two-layer plate structure (aluminum bonded to stainless steel) are reported. The cases of stainless steel atop aluminum and aluminum atop stainless steel are considered. The effects of the second layer on the transient displacement at the top surface are discussed. Finally, a two-layer-on-a-half-space structure consisting of a stainless steel plate as the top layer, an aluminum plate as the second layer and a thick acrylic resin block as the half-space is studied. The obtained experimental transient measurements agree with the computed results for all cases, thus verifying the accuracy of the model.

Journal Article↗