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Biomedical subjects

Y Zhou

Publications and source records attributed to Y Zhou.

At least 19 recordsLinked to original sources

Long latency of evoked quantal transmitter release from somata of locus coeruleus neurons in rat pontine slices.

The locus coeruleus (LC) harbors a compact group of noradrenergic cell bodies projecting to virtually all parts of the central nervous system. By using combined measurements of amperometry and patch-clamp, quantal vesicle release of noradrenaline (NA) was detected as amperometric spikes, after depolarization of the LC neurons. After a pulse depolarization, the average latency of amperometric spikes was 1,870 ms, whereas the latency of glutamate-mediated excitatory postsynaptic currents was 1.6 ms. A substantial fraction of the depolarization-induced amperometric spikes originated from the somata. In contrast to glutamate-mediated excitatory postsynaptic currents, NA secretion was strongly modulated by the action potential frequency (0.5-50 Hz). Somatodendritic NA release from LC upon enhanced cell activity produced autoinhibition of firing and of NA release. We conclude that, in contrast to classic synaptic transmission, quantal NA release from LC somata is characterized by a number of distinct properties, including long latency and high sensitivity to action potential frequency.

Action Potentials↗

Measurements and simulation of forest leaf area index and net primary productivity in Northern China.

Large scale process-based modeling is a useful approach to estimate distributions of global net primary productivity (NPP). In this paper, in order to validate an existing NPP model with observed data at site level, field experiments were conducted at three sites in northern China. One site is located in Qilian Mountain in Gansu Province, and the other two sites are in Changbaishan Natural Reserve and Dunhua County in Jilin Province. Detailed field experiments are discussed and field data are used to validate the simulated NPP. Remotely sensed images including Landsat Enhanced Thematic Mapper plus (ETM+, 30 m spatial resolution in visible and near infrared bands) and Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER, 15m spatial resolution in visible and near infrared bands) are used to derive maps of land cover, leaf area index, and biomass. Based on these maps, field measured data, soil texture and daily meteorological data, NPP of these sites are simulated for year 2001 with the boreal ecosystem productivity simulator (BEPS). The NPP in these sites ranges from 80 to 800 gCm(-2)a(-1). The observed NPP agrees well with the modeled NPP. This study suggests that BEPS can be used to estimate NPP in northern China if remotely sensed images of high spatial resolution are available.

Biomass↗

Observation and simulation of net primary productivity in Qilian Mountain, western China.

We modeled net primary productivity (NPP) at high spatial resolution using an advanced spaceborne thermal emission and reflection radiometer (ASTER) image of a Qilian Mountain study area using the boreal ecosystem productivity simulator (BEPS). Two key driving variables of the model, leaf area index (LAI) and land cover type, were derived from ASTER and moderate resolution imaging spectroradiometer (MODIS) data. Other spatially explicit inputs included daily meteorological data (radiation, precipitation, temperature, humidity), available soil water holding capacity (AWC), and forest biomass. NPP was estimated for coniferous forests and other land cover types in the study area. The result showed that NPP of coniferous forests in the study area was about 4.4 tCha(-1)y(-1). The correlation coefficient between the modeled NPP and ground measurements was 0.84, with a mean relative error of about 13.9%.

Altitude↗

LAI inversion algorithm based on directional reflectance kernels.

Leaf area index (LAI) is an important ecological and environmental parameter. A new LAI algorithm is developed using the principles of ground LAI measurements based on canopy gap fraction. First, the relationship between LAI and gap fraction at various zenith angles is derived from the definition of LAI. Then, the directional gap fraction is acquired from a remote sensing bidirectional reflectance distribution function (BRDF) product. This acquisition is obtained by using a kernel driven model and a large-scale directional gap fraction algorithm. The algorithm has been applied to estimate a LAI distribution in China in mid-July 2002. The ground data acquired from two field experiments in Changbai Mountain and Qilian Mountain were used to validate the algorithm. To resolve the scale discrepancy between high resolution ground observations and low resolution remote sensing data, two TM images with a resolution approaching the size of ground plots were used to relate the coarse resolution LAI map to ground measurements. First, an empirical relationship between the measured LAI and a vegetation index was established. Next, a high resolution LAI map was generated using the relationship. The LAI value of a low resolution pixel was calculated from the area-weighted sum of high resolution LAIs composing the low resolution pixel. The results of this comparison showed that the inversion algorithm has an accuracy of 82%. Factors that may influence the accuracy are also discussed in this paper.

Algorithms↗

Effect of ammonium and nitrate nutrition on some physiological processes in higher plants - growth, photosynthesis, photorespiration, and water relations.

Ammonium and nitrate as different forms of nitrogen nutrients impact differently on some physiological and biochemical processes in higher plants. Compared to nitrate, ammonium results in small root and small leaf area, which may contribute to a low carbon gain, and an inhibition on growth. On the other hand, due to (photo)energy saving, a higher CO (2) assimilation rate per leaf area was observed frequently in plants supplied with ammonium than in those supplied with nitrate. These results were dependent not only on higher Rubisco content and/or activity, but also on RuBP regeneration rate. The difference in morphology such as chloroplast volume and specific leaf weight might be the reason why the CO (2) concentration in the carboxylation site and hence the photorespiration rate differs in plants supplied with the two nitrogen forms. The effect of nitrogen form on water uptake and transportation in plants is dependent both on leaf area or shoot parameter, and on the root activity (i.e., root hydraulic conductivity, aquaporin activity).

Biological Transport↗

Discovery and preliminary structure-activity relationship studies of novel benzotriazine based compounds as Src inhibitors.

We report the discovery and preliminary SAR studies of a series of structurally novel benzotriazine core based small molecules as inhibitors of Src kinase. To the best of our knowledge, benzotriazine template based compounds have not been reported as kinase inhibitors. The 3-(2-(1-pyrrolidinyl)ethoxy)phenyl analogue (43) was identified as one of the most potent inhibitors of Src kinase.

Humans↗

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas.

Ahi-1 (Abelson helper integration site 1) is a novel gene frequently activated by provirus insertional mutagenesis in murine leukemias and lymphomas. Its involvement in human leukemogenesis is demonstrated by gross perturbations in its expression in human leukemia cells, particularly in cutaneous T-cell lymphoma cell lines where increases in AHI-1 transcripts of 40-fold are seen. To test directly whether deregulated expression of AHI-1 contributes to their transformed properties, knockdown of AHI-1 expression in Hut78 cells, a cell line derived from a patient with Sezary syndrome (SS), was performed using retroviral-mediated RNA interference. Retroviral-mediated suppression specifically inhibited expression of AHI-1 and its isoforms in transduced cells by 80% and also reduced autocrine production of interleukin (IL)-2, IL-4 and tumor necrosis factor-alpha (TNFalpha) by up to 85%. It further significantly reduced their growth factor independence in vitro and the ability to produce tumors in immunodeficient mice. Interestingly, aberrant expression of AHI-1, particularly truncated isoforms, was present in CD4+CD7- Sezary cells from some patients with SS. Elevated expression of IL-2 and TNFalpha was also found in these cells. These findings provide strong evidence of the oncogenic activity of AHI-1 in human leukemogenesis and demonstrate that its deregulation may contribute to the development of SS.

Adaptor Proteins, Signal Transducing↗

Scan of human genome reveals no new Loci under ancient balancing selection.

There has been much speculation as to what role balancing selection has played in evolution. In an attempt to identify regions, such as HLA, at which polymorphism has been maintained in the human population for millions of years, we scanned the human genome for regions of high SNP density. We found 16 regions that, outside of HLA and ABO, are the most highly polymorphic regions yet described; however, evidence for balancing selection at these sites is notably lacking--indeed, whole-genome simulations indicate that our findings are expected under neutrality. We propose that (i) because it is rarely stable, long-term balancing selection is an evolutionary oddity, and (ii) when a balanced polymorphism is ancient in origin, the requirements for detection by means of SNP data alone will rarely be met.

ABO Blood-Group System↗

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗

Functional degradation of extrastriate visual cortex in senescent rhesus monkeys.

The receptive field properties of striate cortical (V1) cells degrade in senescent macaque monkeys. We have now carried out extracellular single unit studies of the receptive field properties of cells in extrastriate visual cortex (area V2) in very old rhesus (Macaca mulatta) monkeys. This study provides evidence that both the orientation and direction selectivities of V2 cells in old monkeys degrade significantly. Decreased selectivity is accompanied by increased visually driven and spontaneous responses. As a result, V2 cells in old animals exhibit markedly decreased signal-to-noise ratios. A significant degradation of neural function in extrastriate cortex may underlie the declines in higher order visual function that accompany normal aging.

Action Potentials↗

Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates neuronal damage and astrogliosis after focal cerebral ischemia in rats.

Cysteinyl leukotrienes are potent pro-inflammatory mediators. Cysteinyl leukotriene receptor 1 is one of the two cysteinyl leukotriene receptors cloned. We recently reported that cysteinyl leukotriene receptor 1 antagonists protected against cerebral ischemic injury, and an inducible expression of cysteinyl leukotriene receptor 1 was found in neuron- and glial-appearing cells after traumatic injury in human brain. To determine the role of cysteinyl leukotriene receptor 1 in ischemic brain injury, we investigated the temporal and spatial profile of cysteinyl leukotriene receptor 1 expression in rat brain from 3 h to 14 days after 30 min of middle cerebral artery occlusion, and observed the effect of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, on the ischemic injury. We found that cysteinyl leukotriene receptor 1 mRNA expression was up-regulated in the ischemic core both 3-12 h and 7-14 days, and in the boundary zone 7-14 days after reperfusion. In the ischemic core, cysteinyl leukotriene receptor 1 was primarily localized in neurons 24 h, and in macrophage/microglia 14 days after reperfusion; while in the boundary zone it was localized in proliferated astrocytes 14 days after reperfusion. Pranlukast attenuated neurological deficits, reduced infarct volume and ameliorated neuron loss in the ischemic core 24 h after reperfusion; it reduced infarct volume, ameliorated neuron loss and inhibited astrocyte proliferation in the boundary zone 14 days after reperfusion. Thus, we conclude that cysteinyl leukotriene receptor 1 mediates acute neuronal damage and subacute/chronic astrogliosis after focal cerebral ischemia.

Animals↗

A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer.

X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that -77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between -77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the -77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001) and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21) than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer development owing to the decreased transcriptional activity of C-allele-containing promoter with higher affinity to Sp1 binding.

Adult↗

Wavelet multiresolution analysis of the three vorticity components in a turbulent far wake.

The main objective of the present study is to examine the characteristics of the vortical structures in a turbulent far wake using the wavelet multiresolution technique by decomposing the vorticity into a number of orthogonal wavelet components based on different central frequencies. The three vorticity components were measured simultaneously using an eight-wire probe at three Reynolds numbers, namely 2000, 4000, and 6000. It is found that the dominant contributions to the vorticity variances are from the intermediate and relatively small-scale structures. The contributions from the large and intermediate-scale structures to the vorticity variances decrease with the increase of Reynolds number. The contributions from the small-scale structures to all three vorticity variances jump significantly when Reynolds number is changed from 2000 to 4000, which is connected to previous observations in the near wake that there is a significant increase in the generation of small-scale structures once the Reynolds number reaches about 5000. This result reinforces the conception that turbulence "remembers" its origin.

Journal Article↗

The effect of electrostatic force on the evolution of sand saltation cloud.

In a wind-blown sand layer, it has been found that wind transport of particles is always associated with separation of electric charge. This electrification in turn produces some electrostatic forces in addition to the gravitational and fluid friction forces that affect the movement of saltating sand particles, further, the wind-blown sand saltation. To evaluate this effect quantitatively, this paper presents a simulation of evolution of wind-blown sand grains after the electrostatic forces exerted on the grains are taken into account in the wind feedback mechanism of wind-blown saltation. That is, the coupling interaction between the wind flow and the saltating sand particles is employed in the simulation to the non-stationary wind and sand flows when considering fluid drag, gravitation, and a kind of electrostatic force generated from a distribution of electric field changing with time in the evolution process of the sand saltation. On the basis of the proposed simulation model, a numerical program is given to perform the simulation of this dynamic process and some characteristic quantities, e.g., duration of the system to reach the steady state, and curves of the saltating grain number, grain transport rate, mass-flux profile, and wind profile varying with time during the non-stationary evolution are displayed. The obtained numerical results exhibit that the electrostatic force is closely related to the average charge-to-mass ratio of sand particles and has obvious influence on these characteristic quantities. The obtained results also show that the duration of the system to reach the steady state, the sand transport rate and the mass flux profile coincide well with experimental results by Shao and Raupach (1992) when the average charge-to-mass ratio of sand particles is 60 microC/kg for the sand particles with average diameter of 0.25 mm. When the average charge-to-mass ratios of sand particles are taken as some other certain values, the calculation results still show that the mass flux profiles are well in agreement with the experimental data by Rasmussen and Mikkelsen (1998) for another category of sand particles, which tell us that the electrostatic force is one of main factors that have to be considered in the research of mechanism of wind-blown sand saltation.

Journal Article↗

Increased risk of chronic obstructive pulmonary diseases in coke oven workers: interaction between occupational exposure and smoking.

BACKGROUND: Coke oven workers are regularly exposed to coke oven emissions (COE) and may be at risk of developing lung diseases. There is limited evidence for the link between exposure to COE and chronic obstructive pulmonary diseases (COPD). The aim of this study was to explore the dose-response relationship between COE exposure and COPD and to assess the interaction with cigarette smoking. METHODS: Seven hundred and twelve coke oven workers and 211 controls were investigated in southern China. Benzene soluble fraction (BSF) concentrations as a surrogate of COE were measured in representative personal samples and the individual cumulative COE exposure level was quantitatively estimated. Detailed information on smoking habits and respiratory symptoms was collected and spirometric tests were performed. RESULTS: The mean BSF levels at the top of two coking plants were 743.8 and 190.5 microg/m3, respectively, which exceed the OSHA standard (150 microg/m3). After adjusting for cigarette smoking and other risk factors, there was a significant dose-dependent reduction in lung function and increased risks of chronic cough/phlegm and COPD in coke oven workers. The odds ratio for COPD was 5.80 (95% confidence interval 3.13 to 10.76) for high level cumulative COE exposure (> or =1714.0 microg/m3-years) compared with controls. The interaction between COE exposure and smoking in COPD was significant. The risk of COPD in those with the highest cumulative exposure to COE and cigarette smoking was 58-fold compared with non-smokers not exposed to COE. CONCLUSION: Long term exposure to COE increases the risk of an interaction between COPD and cigarette smoking.

Adult↗

Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase.

Glycogen-synthase kinase-3 (GSK-3) and extracellular signal-regulated kinase (ERK) are critical downstream signaling proteins for the PI3-kinase/Akt and Ras/Raf/MEK-1 pathway, respectively, and regulate diverse cellular processes including embryonic development, cell differentiation and apoptosis. Here, we show that inhibition of GSK-3 using GSK-3 inhibitors or RNA interference (RNAi) significantly induced the phosphorylation of ERK1/2 in human colon cancer cell lines HT29 and Caco-2. Pretreatment with the PKCdelta-selective inhibitor rottlerin or transfection with PKCdelta siRNA attenuated the phosphorylation of ERK1/2 induced by the GSK-3 inhibitor SB-216763 and, furthermore, treatment with SB-216763 or transfection with GSK-3alpha and GSK-3beta siRNA increased PKCdelta activity, thus identifying a role for PKCdelta in the induction of ERK1/2 phosphorylation by GSK-3 inhibition. Treatment with SB-216763 increased expression of cyclooxygenase-2 (COX-2) and IL-8, which are downstream targets of ERK1/2 activation; this induction was abolished by MEK/ERK inhibition, suggesting GSK-3 inhibition induced COX-2 and IL-8 through ERK1/2 activation. The transcriptional induction of COX-2 and IL-8 by GSK-3 inhibition was further demonstrated by the increased COX-2 and IL-8 promoter activity after SB-216763 treatment or transfection with GSK-3alpha or GSK-3beta siRNA. Importantly, our findings identify GSK-3, acting through PKCdelta, as a negative regulator of ERK1/2, thus revealing a novel crosstalk mechanism between these critical signaling pathways.

Apoptosis↗

Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions.

Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas.

Adenoviridae↗