Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 37 records · Page 2Linked to original sources

PubMed2006

Gene amplification and associated loss of 5' regulatory sequences of CoAA in human cancers.

CoAA is an RRM-containing transcriptional coactivator that stimulates transcriptional activation and regulates alternative splicing. We show that the CoAA gene is amplified at the chromosome 11q13 locus in a subset of primary human cancers including non-small cell lung carcinoma, squamous cell skin carcinoma and lymphoma. Analysis of 42 primary tumors suggests that CoAA amplifies independently from the CCND1 locus. Detailed mapping of three CoAA amplicons reveals that the amplified CoAA gene is consistently located at the 5' boundaries of the amplicons. The CoAA coding and basal promoter sequences are retained within the amplicons but upstream silencing sequences are lost. CoAA protein is overexpressed in tumors containing the amplified CoAA gene. RNA dot blot analysis of 100 cases of primary tumors suggests elevated CoAA mRNA expression. CoAA positively regulates its own basal promoter in transfection assays. Thus, gene amplification, loss of silencing sequence and positive feedback regulation may lead to drastic upregulation of CoAA protein. CoAA has transforming activities when tested in soft agar assays, and CoAA is homologous to oncoproteins EWS and TLS, which regulate alternative splicing. These data imply that CoAA may share a similar oncogenic mechanism with oncogene EWS and that CoAA deregulation may alter the alternative splicing of target genes.

Animals↗

PubMed2006

Hernioplasty with bilayer polypropylene mesh: a new tension-free technique.

Different open-mesh techniques have been developed for inguinal hernia repair since the introduction of the tension-free technique. The present study reports a new self-designed tension-free technique for hernioplasty using a bilayer polypropylene mesh. Fifty-one patients with severe transverse fascia weakness were repaired by means of a self-designed, tension-free technique using bilayer polypropylene mesh. The postoperative complications, inpatient hospitalization time, and recurrence rate were studied. Patients were mobilized within 6 h after surgery and no complications were found. The length of hospital stay was 2-3 days. The follow-up period ranged from 3 months to 40 months, with a mean of 20.4 months, and no recurrence was found. Our own experience showed the self-designed, tension-free technique using bilayer polypropylene mesh to be a reliable approach for inguinal hernia repair with many advantages--such as a much lower expense, simplicity, rapid return to unrestricted activities, minor complications, and impressively no recurrence, a particularly superior option for those patients with severe transverse fascia weakness or large defect.

Biocompatible Materials↗

PubMed2006

Rpr1, a gene required for Rpg1-dependent resistance to stem rust in barley.

Rpg1 is a stem rust resistance gene that has protected barley from severe losses for over 60 years in the US and Canada. It confers resistance to many, but not all, pathotypes of the stem rust fungus Puccinia graminis f. sp. tritici. A fast neutron induced deletion mutant, showing susceptibility to stem rust pathotype Pgt-MCC, was identified in barley cv. Morex, which carries Rpg1. Genetic and Rpg1 mRNA and protein expression level analyses showed that the mutation was a suppressor of Rpg1 and was designated Rpr1 (Required for P. graminis resistance). Genome-wide expression profiling, using the Affymetrix Barley1 GeneChip containing approximately 22,840 probe sets, was conducted with Morex and the rpr1 mutant. Of the genes represented on the Barley1 microarray, 20 were up-regulated and 33 were down-regulated by greater than twofold in the mutant, while the Rpg1 mRNA level remained constant. Among the highly down-regulated genes (greater than fourfold), genomic PCR, RT-PCR and Southern analyses identified that three genes (Contig4901_s_at, HU03D17U_s_at, and Contig7061_s_at), were deleted in the rpr1 mutant. These three genes mapped to chromosome 4(4H) bin 5 and co-segregated with the rpr1-mediated susceptible phenotype. The loss of resistance was presumed to be due to a mutation in one or more of these genes. However, the possibility exists that there are other genes within the deletions, which are not represented on the Barley1 GeneChip. The Rpr1 gene was not required for Rpg5- and rpg4-mediated stem rust resistance, indicating that it shows specificity to the Rpg1-mediated resistance pathway.

Blotting, Southern↗

PubMed2006

Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer.

Hedgehog (Hh) signaling pathway is crucial in growth and patterning during embryonic development. Recent data have shown an association of its activation with cancer formation and maintenance. A ligand-dependent activation, where Hh components (SHH, PTCH1, Smo and GLi1) are aberrantly expressed with PTCH1 being a negative feedback regulator, is a newly identified mechanism for pancreatic carcinogenesis. In this study, we developed a cell-specific cytotoxic model for the treatment of human pancreatic cancer (HPC) in which expression of antisense Smo (SAS) was under the control of the PTCH1 promoter (ptch/p) delivered by an adenoviral vector (Ad-ptch/p-SAS). We observed that the cell-specific cytotoxicity in HPC cells depended on the expressions of inherent PTCH1, Smo and GLi1 in the target cells in which the Hh pathway was presumed to be activated. Fluorescence-activated cell sorting analysis indicated that the cell death was apoptosis. Western blot showed that Smo protein in the infected cells significantly decreased. Furthermore, an in vivo experiment demonstrated that such Hh activity-cell-specific cytotoxicity was achieved by daily intratumoral injection of Ad-ptch/p-SAS (10(9) plaque-forming unit) for 5 days. Our study suggests that targeting at the Hh signaling pathway may be an effective novel gene therapeutic strategy alone or in combination with other agents for the treatment of pancreatic cancer.

Adenoviridae↗

PubMed2006

Effect of Cryphonectria hypovirus 1 (CHV1) infection on Cpkk1, a mitogen-activated protein kinase kinase of the filamentous fungus Cryphonectria parasitica.

We screened Cryphonectria parasitica genomic and cDNA libraries with a probe obtained from the amplification of a conserved region among the sequence of known mitogen activated protein kinase kinases (MAPKK) and obtained genomic and cDNA clones. Sequence comparisons of the clones obtained confirmed the identification of a C. parasitica homologue to other fungal MAPKK, which we named Cpkk1. Polyclonal antibodies raised against a purified Cpkk1 fusion protein expressed in Escherichia coli were used to detect Cpkk1 protein in extracts of CHV1-infected and uninfected C. parasitica grown in liquid culture. Differences in the dynamics of phosphorylation and dephosphorylation were noticed. Under the conditions investigated, Cpkk1 protein expression is associated with active mycelial growth, before the onset of a senescent developmental stage. We hypothesize that differences in Cpkk1 phosphorylation state between CHV1 infected and virus free strains are due to a delay of the onset of the developmental stage caused by the presence of the virus.

Amino Acid Sequence↗

PubMed2006

Bidirectional multisite seizure propagation in the intact isolated hippocampus: the multifocality of the seizure "focus".

Localizing the seizure focus is difficult and frequently, multiple sites are found. This reflects our poor understanding of the fundamental mechanisms of seizure generation and propagation. We used multisite electrophysiological recordings in two seizure models and voltage-sensitive dye imaging, to spatiotemporally characterize the initiation and propagation of seizures in an intact epileptogenic brain region, the isolated hippocampus. In low-magnesium perfusate, seizures always originated in the temporal region, and propagated along the septotemporal axis to the septal region. After the seizure spread across the hippocampus, the bursts within a seizure became bidirectional, with different propagation patterns at different frequencies. When the intact hippocampus was separated along the septotemporal axis, independent bidirectional activity was observed in the two halves, and region-specific cuts to the tissue reveal that the CA3 region is critical for seizure generation and propagation. In a second seizure model, using focal tetanic stimulation of the septal and temporal CA3 region, seizures always originated at the stimulated site with bidirectionality later developing at different frequencies, as noted in the low magnesium model, behavior compatible with coupled neuronal network oscillators. These data provide novel insights into the dynamic multifocality of seizure onset and propagation, revealing that the current concept of a single seizure "focus" is complex.

Animals↗

PubMed2006

Suprachiasmatic nucleus communicates with anterior thalamic paraventricular nucleus neurons via rapid glutamatergic and gabaergic neurotransmission: state-dependent response patterns observed in vitro.

The hypothalamic suprachiasmatic nucleus uniquely projects to the midline thalamic paraventricular nucleus. To characterize this projection, patch clamp techniques applied in acute rat brain slice preparations examined responses of anterior thalamic paraventricular nucleus neurons to focal suprachiasmatic nucleus stimulation. Whole cell recordings from slices obtained during daytime (n=40) revealed neurons with a mean membrane potential of -66+/-1.2 mV, input conductance of 1.5+/-0.1 nS and state-dependent tonic or burst firing patterns. Electrical stimulation (one or four pulses) in suprachiasmatic nucleus elicited monosynaptic excitatory postsynaptic potentials (mean latency of 12.6+/-0.6 ms; n=12), featuring both AMPA and N-methyl-D-aspartate-glutamate receptor-mediated components, and monosynaptic bicuculline-sensitive inhibitory postsynaptic potentials (mean latency of 16.6+/-0.6 ms; n=7) reversing polarity at -72+/-2.6 mV, close to the chloride equilibrium potential. Glutamate microstimulation of suprachiasmatic nucleus also elicited transient increases in spontaneous excitatory or inhibitory postsynaptic currents in anterior thalamic paraventricular neurons. Recordings from rats under reverse light/dark conditions (n=22) yielded essentially similar responses to electrical stimulation. At depolarized membrane potentials, suprachiasmatic nucleus-evoked excitatory postsynaptic potentials triggered single action potentials, while evoked inhibitory postsynaptic potentials elicited a silent period in ongoing tonic firing. By contrast, after manual adjustment of membrane potentials to hyperpolarized levels, neuronal response to the same "excitatory" stimulus was a low threshold spike and superimposed burst firing, while responses to "inhibitory" stimuli paradoxically elicited excitatory rebound low threshold spikes and burst firing. These data support the existence of glutamatergic and GABAergic efferents from the suprachiasmatic nucleus to its target neurons. Additionally, in thalamic paraventricular nucleus neurons, responses to activation of their suprachiasmatic afferents may vary in accordance with their membrane potential-dependent intrinsic properties, a characteristic typical of thalamocortical neurons.

Animals↗

PubMed2006

Endothelial nitric oxide synthase mediates protective effects of hypoxic preconditioning in lungs.

To elucidate the protective mechanism of whole-body hypoxic preconditioning (WHPC) on pulmonary ischemia-reperfusion injury focussing on nitric oxide synthases (NOS), mice were placed in a hypoxic chamber (FIO(2)=0.1) for 4h followed by 12h of normoxia. Then, pulmonary ischemia for 1h followed by 5h of reperfusion was performed by clamping the left hilum in vivo (I/R). WHPC protected WT mice from pulmonary leukocyte infiltration as assessed by myeloperoxidase (MPO) activity, associated with a mild further increase in endothelial permeability (Evans Blue extravasation). When all NOS isoforms were inhibited during WHPC by L-NAME, mortality and MPO activity after I/R markedly increased. To determine the responsible NOS isoform, quantitative RT-PCR was performed for eNOS and iNOS mRNA, showing that only eNOS was upregulated in response to WHPC. While eNOS total protein expression remained unchanged, the amount of phosphorylated eNOS also increased. The WHPC/IR experiments were then repeated with eNOS knockout mice. Here, we found that the protective effect of WHPC on pulmonary leukocyte sequestration was abrogated, and endothelial leakage was further exacerbated. We conclude that WHPC limits neutrophil sequestration via an eNOS-dependent mechanism, and that eNOS helps preserve endothelial permeability during hypoxia and I/R.

Animals↗

PubMed2006

Diverse signals converge at MAPK cascades in plant.

Mitogen-activated protein kinases (MAPKs) are important signal transducing enzymes that connects diverse receptors/sensors to a wide range of cellular responses in mammals, yeasts and plants. In recent years, a large number of different components of plant MAPK cascades were isolated. Molecular and biochemical studies have revealed that plant MAPKs play important role in the response to a broad variety of biotic and abiotic stresses, including wounding, pathogen infection, temperature, drought, salinity, but also in the signaling of plant hormones and the cell division. This review briefly summaries the recent research results about the cross-talk and complexity of MAP kinase cascades in plant obtained from functional analyses.

Acclimatization↗

PubMed2006

Observation of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S) and pi(+)pi(-)Upsilon(2S).

Observation of Upsilon(4S) decays to pi(+)pi(-)C and pi(+)pi(-)Upsilon(2S)We present the first measurement of Upsilon(4S) decays to pi(+)pi(-)Upsilon(1S) based on a sample of 230 x 106(4S) mesons collected with the BABAR detector. We measure the product branching fractions Beta(Upsilon(4S) --> pi(+)pi(-)Upsilon(1S)) x BetaUpsilon(1S) --> mu(+)mu(-) = (2.23 +/- 0.25(stat) +/- 0.27(syst))x 10(-6) and Beta(Upsilon(4S) --> pi(+)pi(-)Upsilon(2S) x Beta(Upsilon(2S) --> mu(+)mu(-))=(1.69 +/-0.26(stat) +/- 0.20(syst)) x 10(-)6, from which we derive the partial widths Gamma(Upsilon(4S) --> pi(+)pi(-)Upsilon(1S))=(1.8 +/-0.4) keV and Gamma(Upsilon(4S) --> pi(+)pi(-)Upsilon(2S))=(2.7 +/- 0.8) keV.

Journal Article↗

PubMed2006

Identification of a region on the outer surface of the CBFbeta-SMMHC myeloid oncoprotein assembly competence domain critical for multimerization.

In the core binding factor (CBF)beta-smooth muscle myosin heavy chain (SMMHC) acute myeloid leukemia (AML) oncoprotein, CBFbeta lies N-terminal to the alpha-helical rod domain of SMMHC. Deletion of the SMMHC assembly competence domain (ACD), conserved among skeletal, smooth and nonmuscle myosins, prevents multimerization, inhibition of CBF and inhibition of cell proliferation. To define the amino acids critical for ACD function, three outer surface residues of ACD helices A-D, the subsequent helices E-H or the more N-terminal X or Z helices were now mutated. Variants were assessed for multimerization in low ionic strength in vitro and for nuclear localization as a measure of in vivo multimerization. Mutation of individual helices C-H reduced multimerization, with alteration of the outer surface of helices D or E having the greatest effect. The ability of these SMMHC variants to slow murine myeloid progenitor proliferation largely paralleled their effects on multimerization. Divergence at the boundaries of the ACD may reflect quantitative differences between in vitro and in vivo filament assembly. Each helix mutant retained the ability to bind the mSin3A corepressor. Agents interacting with the outer surface of the CBFbeta-SMMHC ACD that prevent multimerization may be effective as novel therapeutics in AML.

Amino Acid Sequence↗

PubMed2006

Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones.

Spinal motoneurons, like many neurons, respond with repetitive spiking to sustained inputs. The afterhyperpolarization (AHP) that follows each spike, however, decays relatively slowly in motoneurons. The slow depolarization during this decay should allow sodium (Na+) channel inactivation to keep up with its activation and thus should prevent initiation of the next spike. We hypothesized that the persistent component of the total Na+ current provides the mechanism that generates a rate of rise sufficiently rapid to generate a spike. In large cultured spinal neurons, presumed to be primarily motoneurons, inhibition of persistent sodium current (NaP) by the drug riluzole at low concentrations resulted in a loss of repetitive firing. However, cells remained fully capable of producing spikes to transient inputs. These effects of riluzole were not due to insufficient depolarization, enhancement of the AHP, or sustained Na+ channel inactivation. To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of NaP relative to transient Na+ current (NaT) than that provided by riluzole administration. The model was tuned to generate substantial NaP and exhibited good repetitive firing to slowly rising inputs. When NaP was sharply reduced without significantly altering NaT, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients. These results strongly support the essential role of NaP in spike initiation to slow inputs in spinal neurons. NaP may play a fundamental role in determining how a neuron responds to sustained inputs.

Action Potentials↗

PubMed2006

Trimethyltin-induced apoptosis is associated with upregulation of inducible nitric oxide synthase and Bax in a hippocampal cell line.

Trimethyltin (TMT) produces selective neuronal degeneration in the central nervous system (CNS), in which the hippocampus is the most sensitive area. Since previous studies have been conducted in either non-neural cells or mixed primary cultures, an immortalized hippocampal neuronal cell line (HT-22 cell) was used to assess the mechanism and mode of death produced by TMT. The compound produced a time- and concentration-dependent apoptotic death that was caspase-mediated. Excessive generation of reactive oxygen species (ROS) and subsequent reduction of mitochondrial membrane potential (DeltaPsim) were involved in the cytotoxicity. Scavenging of ROS by a free radical trapping agent or inhibition of the mitochondrial permeability transition (MPT) pore significantly reduced cell death. Additionally, TMT increased expression of inducible nitric oxide synthase (iNOS) by activation of the redox-sensitive transcription factor NFkappaB. Pharmacologic inhibition studies showed that the iNOS-mediated NO generation increased expression of Bax and then mitochondrial-mediated apoptosis. It was concluded that excessive ROS generation initiated the apoptotic cell death by upregulating iNOS followed by increased Bax expression which then led to loss of DeltaPsim and caspase-executed cell death. This study is the first to report in a neuronal cell model that TMT stimulates induction of iNOS, which then increases cellular levels of reactive nitrogen species (RNS) to initiate apoptotic death.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Prevention of murine experimental autoimmune encephalomyelitis by in vivo expression of a novel recombinant immunotoxin DT390-RANTES.

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease. Chemokine receptor CCR5 has been shown to be essential for the T-cell recruitment to the inflammatory site in EAE. In this study, we assumed that an immunotoxin directed at CCR5+ cells would be able to reduce the disease activity of EAE. A recombinant immunotoxin, DT390-RANTES-SRalpha, was constructed in an eukaryotic cell expression plasmid consisting of regulated on activation normal T cells expressed and secreted (RANTES) as the targeting moiety and DT390 as the toxic moiety. DT390-RANTES was expressed in vitro and was highly toxic to activated mouse T cells with the inhibitory concentration 50 at 0.18 ng/ml. To evaluate whether DT390-RANTES was effective in preventing EAE, C57BL/6 mice were immunized with myelin basic protein, emulsified with complete Freund's adjuvant and were treated by injecting cationic liposome-embedded plasmid DNA into the muscle of hind limbs. Mice treated with DT390-RANTES-SRalpha developed a much milder EAE compared to mice treated with phosphate-buffered saline or the empty plasmid DNA. Much less CCR5+-infiltrating cells were found in the central nervous system in DT390-RANTES-SRalpha-treated mice than in the control mice. This study indicates that recombinant immunotoxin can be expressed in vivo, and targeting CCR5 can attenuate the disease activity of EAE in mice.

3T3 Cells↗

PubMed2006

Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma.

MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors.

Animals↗

PubMed2006

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↗

PubMed2006

F-box protein Skp2: a novel transcriptional target of E2F.

The F-box-containing protein Skp2 plays a critical role in coordinating the G1/S transition and progression through the S phase of the mammalian cell cycle. Skp2 is overexpressed in a broad spectrum of human cancers and the expression level correlates with tumor malignancy. However, the Skp2 gene is neither amplified nor rearranged in most human cancers and the underlying mechanism of Skp2 overexpression remains poorly understood. We show here that the Skp2 gene contains a functional E2F response element (hSRE2). Ectopic expression of E2F1 induces expression of the endogenous Skp2 gene in human fibroblast cells, whereas antisense-mediated knockdown of E2F1 in human tumor cell lines reduces expression of endogenous Skp2 gene. The hSRE2 element not only participates in activation of Skp2 promoter function during normal cell cycle progression into S phase, it is also required for the high-level Skp2 gene expression in many human tumor cell lines. These results reveal Skp2 as a novel target for E2F regulation that is disrupted in several human tumor cell lines.

Animals↗

PubMed2006

Gene expression profiling reveals the profound upregulation of hypoxia-responsive genes in primary human astrocytes.

Oxygen is vital for the development and survival of mammals. In response to hypoxia, the brain initiates numerous adaptive responses at the organ level as well as at the molecular and cellular levels, including the alteration of gene expression. Astrocytes play critical roles in the proper functioning of the brain; thus the manner in which astrocytes respond to hypoxia is likely important in determining the outcome of brain hypoxia. Here, we used microarray gene expression profiling and data-analysis algorithms to identify and analyze hypoxia-responsive genes in primary human astrocytes. We also compared gene expression patterns in astrocytes with those in human HeLa cells and pulmonary artery endothelial cells (ECs). Remarkably, in astrocytes, five times as many genes were induced as suppressed, whereas in HeLa and pulmonary ECs, as many as or more genes were suppressed than induced. More genes encoding hypoxia-inducible functions, such as glycolytic enzymes and angiogenic growth factors, were strongly induced in astrocytes compared with HeLa cells. Furthermore, gene ontology and computational algorithms revealed that many target genes of the EGF and insulin signaling pathways and the transcriptional regulators Myc, Jun, and p53 were selectively altered by hypoxia in astrocytes. Indeed, Western blot analysis confirmed that two major signal transducers mediating insulin and EGF action, Akt and MEK1/2, were activated by hypoxia in astrocytes. These results provide a global view of the signaling and regulatory network mediating oxygen regulation in human astrocytes.

Algorithms↗