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M Ding

Publications and source records attributed to M Ding.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evaluating causal relations in neural systems: granger causality, directed transfer function and statistical assessment of significance.

We consider the question of evaluating causal relations among neurobiological signals. In particular, we study the relation between the directed transfer function (DTF) and the well-accepted Granger causality, and show that DTF can be interpreted within the framework of Granger causality. In addition, we propose a method to assess the significance of causality measures. Finally, we demonstrate the applications of these measures to simulated data and actual neurobiological recordings.

Action Potentials↗
PubMed2001

Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic.

The objective of the present study was (1) to test the hypothesis that the elastic and failure properties of the cancellous bone of the mandibular condyle depend on the loading direction, and (2) to relate these properties to bone density parameters. Uniaxial compression tests were performed on cylindrical specimens (n=47) obtained from the condyles of 24 embalmed cadavers. Two loading directions were examined, i.e., a direction coinciding with the predominant orientation of the plate-like trabeculae (axial loading) and a direction perpendicular to the plate-like trabeculae (transverse loading). Archimedes' principle was applied to determine bone density parameters. The cancellous bone was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than in transverse loading. High coefficients of correlation were found among the various mechanical properties and between them and the apparent density and volume fraction. The anisotropic mechanical properties can possibly be considered as a mechanical adaptation to the loading of the condyle in vivo.

Aged↗
PubMed2001

The coatomer of Trypanosoma brucei.

Coatomer is a multisubunit complex involved in trafficking of vesicles between the endoplasmatic reticulum and the Golgi apparatus. From sequence homologies, all seven subunits, alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP, are encoded in the genome of Trypanosoma brucei. The complete predicted amino-acid sequences of beta-, beta'-, and zeta-COP show only 20-30% identity with higher eucaryotic homologues. The trypanosome coatomer complex was partially purified using a procedure similar to that used for bovine coatomer.

Amino Acid Sequence↗
PubMed2001

A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

Aged↗
PubMed2001

Bone density does not reflect mechanical properties in early-stage arthrosis.

Subchondral cancellous bone specimens were removed from 10 human postmortem early-stage arthrotic proximal tibiae (mean age 73 (63-81) years) and 10 age- and gender-matched normal proximal tibiae. The early-stage arthrosis was confirmed histologically and the specimens were divided into 4 groups: medial arthrosis, lateral control, normal medial and normal lateral controls. The specimens were tested in compression to determine mechanical properties and then physical/compositional properties. Compared to the normal medial control, we found reductions in ultimate stress, Young's modulus, and failure energy, and an increase in ultimate strain of arthrotic cancellous bone. Bone volume fraction, apparent density, apparent ash density, and collagen density were higher in cancellous bone with arthrosis, but no differences were found in tissue density, mineral and collagen concentrations between arthrotic cancellous bone and the 3 controls. None of the mechanical properties of arthrotic cancellous bone could be predicted by the physical/compositional properties measured. The increase in bone tissue in early-stage arthrotic cancellous bone did not make up for the loss of mechanical properties, which suggests a deterioration in the quality of arthrotic cancellous bone.

Aged↗
PubMed2001

Origins of timing errors in human sensorimotor coordination.

The authors analyzed fluctuations in timing errors when 8 human participants attempted to coordinate movement with external rhythmic signals. The temporal dynamics of the errors is usually described in terms of simple, self-correcting models. Here the authors demonstrate that timing errors are characterized by a 1/f(alpha) type of long memory process. The value of the exponent alpha differentiates different types of coordination states: synchronization and syncopation. More interesting, evidence was found that alpha can be changed when participants use different coordination strategies. Together with the authors' understanding of the generation mechanism for long memory processes, these results suggest that 1/f(alpha) type of long-range correlated timing errors are of higher cortical origin and are likely the outcome of distributed neural processes acting on multiple time scales.

Brain↗
PubMed2001

Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences.

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viral env from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C(IN). Overall, C(IN) lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-C(IN) sequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

Adult↗
PubMed2001

Reactive oxygen species and molecular mechanism of silica-induced lung injury.

Silica particles are considered to be fibrogenic and carcinogenic agents, but the mechanisms of disease initiation and progression are not fully understood. This article summarizes the literature on the generation of reactive oxygen species (ROS) directly from interaction of silica with aqueous medium and from silica-stimulated cells. This article also discusses the role of ROS in silica-induced lung injury, with particular focus on the silica-induced NF-kappaB activation, including the molecular mechanisms of its regulation, its possible attenuation, and its relationship to silica-induced generation of cyclooxygenase II and TNF-alpha.

Air Pollutants, Occupational↗
PubMed2001

Transactivation of RARE and GRE in the cellular response to arsenic.

Arsenic compounds are a somewhat unique class of metals, which have been considered as both carcinogens and chemotherapeutic agents for cancers. Tumor promotion effects of arsenic are believed to be associated with its transactivational activities on transcription factors, such as AP-1 and NFkappaB, while the induction of cell apoptosis and differentiation by arsenic is considered to be a mechanism for the chemotherapeutic effects of arsenic. Here, we found that exposure of cells to arsenite and arsenate leads to transactivation of retinoic acid response elements (RARE) and glucocorticoid response elements (GRE) in mouse epidermal JB6 cells. These inductions occur in a time-dependent manner. Furthermore, induction of RARE activity by arsenic was synergistically enhanced by co-treatment of cells with retinoic acid, while GRE activation by arsenic was not affected by combined treatment of cells with fluocinolone acetonide (FA). In consideration of the important role of RARE and GRE in induction of cell differentiation, we speculate that transactivation of RARE and GRE by arsenic may be involved in its induction of cell differentiation and anti-cancer activities in addition to its induction of apoptosis.

Animals↗
PubMed2001

Carcinogenic metals and NF-kappaB activation.

Epidemiological and animal studies suggest that several metals and metal-containing compounds are potent mutagens and carcinogens. These metals include chromium, arsenic, vanadium, and nickel. During the last two decades, chemical and cellular studies have contributed enormously to our understanding of the mechanisms of metal-induced pathophysiological processes. Although each of these metals is unique in its mechanism of action, some common signaling molecules, such as reactive oxygen species (ROS), may be shared by many of these carcinogenic metals. New techniques are now available to reveal the mechanisms of carcinogenesis in precise molecular terms. In this review, we focused our attentions on metal-induced signal transduction pathways leading to the activation of NF-kappaB, a transcription factor governing the expression of most early response genes involved in a number of human diseases.

Animals↗
PubMed2001

On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses.

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 microM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of transcription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non-radioactive ELISA kit. At the concentration range used in the present study, no thresholds were found in all of these cell responses to Cr (VI). The results may guide further research to better understand and evaluate the risk of Cr (VI)-induced carcinogenesis at low levels of exposure.

Antioxidants↗
PubMed2001

Arsenic-induced NFkappaB transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells.

Tumor promoting effects of arsenic are believed to be associated with its transactivation activity on transcription factors, such as AP-1 and NFkappaB. However, the results from different groups studying the effects of arsenic on NFkappaB activation are contradictory in different cell models. Since arsenic is a strong skin carcinogen, we have investigated the activation of NFkappaB by arsenic in a mouse skin epidermal cell line, JB6 cells. Exposure of cells to arsenite or arsenate led to NFkappaB transactivation in mouse epidermal JB6 NFkappaB-luciferase reporter stable transfectants, C141 NFkappaB mass1. This induction of NFkappaB activity by arsenic was dose- and time-dependent. The transactivation of NFkappaB by arsenic appeared to be through activation of Erks and JNKs pathways because increased NFkappaB activity by arsenic could be dramatically inhibited by either pre-treatment of cells with PD98059 or overexpression of dominant negative JNK1. That Erks activation is required for arsenic-induced NFkappaB transactivation was further supported by the findings that arsenic-induced NFkappaB transactivation was impaired in JB6 30.7b cells, which were deficient in Erks.

Animals↗
PubMed2001

[Construction of the full-length cDNA clone of Chinese virulent strain--F114].

Seven subclones covered the complete genome of classical swine fever virus Chinese virulent strain F114 were obtained by reverse transcription PCR. The complete nucleotide sequence of the genome of strain F114 was determined by sequencing. The cDNA fragments were then assembled and inserted downstream of a T7 promoter in pBluescript II sk+ plasmid vector to obtain the full-length cD-NA clone sk-12297. Homology comparison of the nucleotide and amino acid sequence of strain F114 with the known sequences of HCLV, Brescia and Alfort showed 95.70%, 96.80%, 86.03% identity in nucleotide and 97.41%, 98.54%, 93.33% identity in amino acid respectively.

Animals↗
PubMed2000

Induction of activator protein-1 through reactive oxygen species by crystalline silica in JB6 cells.

We reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. We found that FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and oxygen consumption support the conclusion that ROS are generated by silica-treated cells. N-Acetylcysteine (an antioxidant) and polyvinyl pyridine-N-oxide (an agent that binds to Si-OH groups on silica surfaces) decreased AP-1 activation and phosphorylation of ERKs and p38 kinase. Catalase inhibited phosphorylation of ERKs and p38 kinase, as well as AP-1 activation induced by FFSi, suggesting the involvement of H(2)O(2) in the mechanism of silica-induced AP-1 activation. Sodium formate (an ( small middle dot)OH scavenger) had no influence on silica-induced MAPKs or AP-1 activation. Superoxide dismutase enhanced both AP-1 and MAPKs activation, indicating that H(2)O(2), but not O(2), may play a critical role in silica-induced AP-1 activation. These studies indicate that freshly ground silica is more biologically active than aged silica and that ROS, in particular H(2)O(2), play a significant role in silica-induced AP-1 activation.

Animals↗
PubMed2000

Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis.

Vanadium is a metal widely distributed in the environment. Although vanadate-containing compounds exert potent toxic effects on a wide variety of biological systems, the mechanisms controlling vanadate-induced adverse effects remain to be elucidated. The present study investigated the vanadate-induced p53 activation and involvement of reactive oxygen species (ROS) in p53 activation as well as the role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6 cells to vanadate led to transactivation of p53 activity in a time- and dose-dependent manner. It also caused mitochondrial damage, apoptosis, and generated ROS. Scavenging of vanadate-induced H(2)O(2) by N-acetyl-l-cysteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor), or the chelation of vanadate by deferoxamine, resulted in inhibition of p53 activation and cell mitochondrial damage. In contract, an increase in H(2)O(2) generation in response to superoxide dismutase or NADPH enhanced these effects caused by vanadate. Furthermore, vanadate-induced apoptosis occurred in cells expressing wild-type p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results demonstrate that vanadate induces p53 activation mainly through H(2)O(2) generation, and this activation is required for vanadate-induced apoptosis.

Acetylcysteine↗