Biomedical subjects

Jianhong Wu

Publications and source records attributed to Jianhong Wu.

17 recordsLinked to original sources

PubMed2006

Eradicating vector-borne diseases via age-structured culling.

We derive appropriate mathematical models to assess the effectiveness of culling as a tool to eradicate vector-borne diseases. The model, focused on the culling strategies determined by the stages during the development of the vector, becomes either a system of autonomous delay differential equations with impulses (in the case where the adult vector is subject to culling) or a system of nonautonomous delay differential equations where the time-varying coefficients are determined by the culling times and rates (in the case where only the immature vector is subject to culling). Sufficient conditions are derived to ensure eradication of the disease, and simulations are provided to compare the effectiveness of larvicides and insecticide sprays for the control of West Nile virus. We show that eradication of vector-borne diseases is possible by culling the vector at either the immature or the mature phase, even though the size of the vector is oscillating and above a certain level.

Age Factors↗

PubMed2006

Fifty years later: A neurodynamic explanation of Fitts' law.

An intrinsic property of human motor behaviour is a trade-off between speed and accuracy. This is classically described by Fitts' law, a model derived by assuming the human body has a limited capacity to transmit information in organizing motor behaviour. Here, we propose an alternative foundation, based on the neurodynamics of the motor circuit, wherein Fitts' law is an approximation to a more general relationship. In this formulation, widely observed inconsistencies with experimental data are a consequence of psychomotor delay. The methodology developed additionally provides a method to estimate the delay within the motor circuit from the speed-accuracy trade-off alone.

Humans↗

PubMed2006

Topoisomerase IIIalpha and Bloom's helicase can resolve a mobile double Holliday junction substrate through convergent branch migration.

It has long been suspected that a double Holliday junction (dHJ) could be resolved by a topoisomerase partnered with a helicase by convergent branch migration of the HJs. Genetic analysis of yeast TOP3 and SGS1 has lent considerable evidence to the notion that the protein products of these genes are involved in just such a process, although biochemical analysis of the metabolism of a dHJ has been hindered by the lack of a substrate that adequately replicates the endogenous structure. We have synthesized a dHJ substrate that recapitulates many of the features of an endogenous dHJ and represents a much earlier intermediate in the resolution pathway. Here, we show that Drosophila topoisomerase IIIalpha (Topo IIIalpha) and Blm (a homolog of Sgs1) are capable of resolving this substrate to non-cross-over products and that this activity is stimulated by replication protein A (RPA). We investigated the ability of other Drosophila topoisomerases to perform this reaction in concert with Blm and RPA and discovered that this resolution activity is unique to Topo IIIalpha. Examination of the mechanism of resolution reveals that Topo IIIalpha, Blm, and RPA resolve this substrate by convergent migration of the two HJs toward each other, collapsing the dHJ. This mechanism stands in contrast to classic resolvase activities that use a structure-specific endonuclease to cleave the HJs.

Animals↗

PubMed2006

Speed-accuracy trade-off in planned arm movements with delayed feedback.

The Vector Integration to Endpoint (VITE) circuit describes a real-time neural network model simulating behavioral and neurobiological properties of planned arm and hand movements by the interaction of two populations of neurons. We analyze the speed-accuracy trade-off generated by this circuit, generalized to include delayed feedback. With delay, two important new properties of the circuit emerge: a breakdown of Fitts' law when the movement time is small relative to the delay; and a positive Fitts' law Y-intercept. This breakdown of Fitts' law for tasks with small Index of Difficulty has been previously observed experimentally, and we suggest it may be attributed at least in part to delay effects in the nervous system elaborated by the model. Additionally, this gives a theoretical explanation for why positive Fitts' law Y-intercept should occur, and that it is related to the delay within the movement circuit.

Arm↗

PubMed2006

Simple models for containment of a pandemic.

Stochastic simulations of network models have become the standard approach to studying epidemics. We show that many of the predictions of these models can also be obtained from simple classical deterministic compartmental models. We suggest that simple models may be a better way to plan for a threatening pandemic with location and parameters as yet unknown, reserving more detailed network models for disease outbreaks already underway in localities where the social networks are well identified.We formulate compartmental models to describe outbreaks of influenza and attempt to manage a disease outbreak by vaccination or antiviral treatment. The models give an important prediction that may not have been noticed in other models, namely that the number of doses of antiviral treatment required is extremely sensitive to the number of initial infectives. This suggests that the actual number of doses needed cannot be estimated with any degree of reliability. The model is applicable to pre-epidemic vaccination, such as annual vaccination programs in anticipation of an 'ordinary' influenza outbreak with limited drift, and as a combination of treatment both before and during an epidemic.

Antiviral Agents↗

PubMed2006

A new Drosophila gene wh (wuho) with WD40 repeats is essential for spermatogenesis and has maximal expression in hub cells.

Through mutagenesis by P-element transposition, we identified a series of mutants with deletions in topoisomerase 3beta gene (top3beta) and an adjacent, previously uncharacterized gene CG15897, here named wuho (wh). Whereas top3beta truncation does not affect viability or fertility, wh null mutants display male sterile and female semi-sterile phenotypes. Furthermore, wh mutants can be fully rescued by wh transgenes, but not by top3beta transgenes, suggesting that the fertility phenotypes are caused by wh deletion. The alignment of WH protein sequence with other eukaryotic putative homologues shows they are evolutionarily conserved proteins with 5 WD40 repeats in the middle portion of the protein, and a bipartite nuclear localization signal at the carboxyl terminus. Yeast homologue with 5 WD40 repeats, Trm82, is the non-catalytic subunit of a tRNA methylase. Immunostaining shows that WH has the highest expression in hub cells, a niche for germline stem cells of testis. However, WH is not required for the maintenance of hub cells or the germline stem cells. In wh mutant males, spermatogenesis is arrested at the elongating stage of the developing spermatids, resulting in an absence of mature sperms in the seminal vesicles. The decreased fertility in wh mutant females is mostly due to defects in oogenesis. There are abnormal egg chambers present in the mutant females, in which the cystocytes fail to arrest their cell division at the fourth mitotic cycle, resulting in more than 16 cells in a single egg chamber. Additionally, these abnormal cystocytes do not undergo multiple rounds of endoreplication as the nurse cells do in a normal egg chamber. Therefore, the cytological analyses demonstrate that wh has a critical function in cellular differentiation for germline cells during gametogenesis.

Amino Acid Sequence↗

PubMed2006

When is quarantine a useful control strategy for emerging infectious diseases?

The isolation and treatment of symptomatic individuals, coupled with the quarantining of individuals that have a high risk of having been infected, constitute two commonly used epidemic control measures. Although isolation is probably always a desirable public health measure, quarantine is more controversial. Mass quarantine can inflict significant social, psychological, and economic costs without resulting in the detection of many infected individuals. The authors use probabilistic models to determine the conditions under which quarantine is expected to be useful. Results demonstrate that the number of infections averted (per initially infected individual) through the use of quarantine is expected to be very low provided that isolation is effective, but it increases abruptly and at an accelerating rate as the effectiveness of isolation diminishes. When isolation is ineffective, the use of quarantine will be most beneficial when there is significant asymptomatic transmission and if the asymptomatic period is neither very long nor very short.

Communicable Diseases, Emerging↗

PubMed2005

Standard and quantitative analysis of cyclin E threshold by cyclin E/DNA multiparameter flow cytometry.

The threshold of cyclin E expression at G1/S boundary is a characteristic feature of cell cycle progressing. In this study, we tried to develop a quantitative approach to analyze cyclin E threshold by multiparameter flow cytometry. The expression of cyclin E in exponentially growing MOLT-4 cells was detected under different photomultiplier tube (PMT) voltages by cyclin E/DNA multiparameter flow cytometry. Additionally, cyclin E was detected in cells which were treated with caffeine and cycloheximide (CHX) under the same PMT voltage. Moreover, the expression of cyclin E in MOLT-4 cells was compared with that in JURKAT cells. Cyclin E threshold was quantified by formula B2/AxC (A, B, C indicates the minimum, threshold, and maximum of cyclin E fluorescence intensity, respectively). Results showed that in MOLT-4 cells, cyclin E threshold calculated by formula B2/AxC was invariable under different PMT settings. It was decreased in cells treated with caffeine and remained changeless in cells treated with cycloheximide. Cyclin E threshold in JURKAT cells was much lower than that in MOLT-4 cells. It was suggested that Formula B2/AxC we firstly set up could be used to analyze cyclin E expression threshold quantitatively.

Caffeine↗

PubMed2005

Apoptotic sensitivity to irradiation increased after transfection of chk1 antisense chain to HL-60 cell line.

The HL-60 cells were transfected with chk1 antisense and sense chain, and 24 h later subjected to irradiation. Twenty-four h after irradiation, the changes in the chk1 protein expression was assayed by Western blot, and the cell cycles and apoptosis rate detected by FCM. The irradiated apoptosis sensitivity was increased by antisense blocking of chk1 gene in HL-60 cell line with the apoptosis rate being 26.31%, significantly higher than that by the sense blocking (10.34%, 0.025 < P < 0.05). In HL-60 cells transfected with chk1 antisense chain, the G2/M phase arrest was attenuated and the cells in G2/M phase were accounted for 38.42%, significantly lower than those of the cells transfected with chkl sense chain (54.64%, 0.005 < P < 0.01). It was concluded that antisense blocking of chk1 gene could increase the apoptosis sensitivity to irradiation.

Apoptosis↗

PubMed2005

Subcellular localization of caspase-3 activation correlates with changes in apoptotic morphology in MOLT-4 leukemia cells exposed to X-ray irradiation.

Caspase-3 is a critical effector caspase for apoptosis, which cleaves proteins, including cytoskeletal and associated proteins, kinases, and members of the Bcl-2 family of apoptosis-related proteins. This leads to changes in apoptotic morphology, such as membrane externalization and cytoplasm and nuclear condensation. It has been reported that pro-caspase-3 is activated in the cytosol. However, it remains obscure how caspase-3 activation correlates to serial changes in cell morphology during apoptosis. The current study was therefore undertaken to assess the relationship between caspase-3 activation and its subcellular localization and alterations in apoptotic morphology in MOLT-4 human leukemia cells exposed to X-ray irradiation. Fluorescence labeled inhibitor of caspases (FLICA) was used to detect caspase-3 activity in apoptotic cells in this project; cell morphology and caspase-3 sub-localization were determined by confocal microscopy. Our data showed that MOLT-4 cells presented typical morphological changes in apoptosis, such as membrane reversion, DNA fragmentation, and formation of apoptotic cell bodies following 10 Gray (Gy) of X-ray irradiation. Caspase-3 was activated 2 h after X-ray irradiation, and its activity increased markedly after 4-6-h exposure. Membrane reversion in MOLT-4 leukemia cells was detected by Annexin V assay at 4 h following X-ray irradiation, 2 h after the elevated caspase-3 activity was measured. Cytologically, activation of caspase-3 was first observed close to the inside surface of the cellular membrane, then transferred to the cytoplasm, and finally translocated to the nuclear region. We conclude that caspase-3 is activated in MOLT-4 cells following exposure to X-rays, and that the enhanced caspase-3 activity and its sub-localization shifting is correlated to changes in apoptotic morphology. The spatial shift of activated caspase-3 in X-ray-induced apoptotic MOLT-4 leukemia cells is a process of crucial importance for apoptosis.

Apoptosis↗

PubMed2005

Differential expression of cyclins A, B1, D3 and E in G1 phase of the cell cycle between the synchronized and asynchronously growing MOLT-4 cells.

The use of 'double-thymidine block' was the first widely accepted method for inducing cell synchrony and remains one of the most effective and frequently used techniques for analyzing the cell cycle today. While thymidine is in itself an inhibitor of DNA replication, thymidine blocks are typically used to generate cell synchrony at the G1/S boundary. We have previously presented the first evidence that shows the growth imbalance and altered expression levels of cyclins A, B1, D3 and E in MOLT-4 cells synchronized in the cell cycle by thymidine. The major objective of the present study was to compare the levels of cyclins A, B1, D3 and E in G1 phase of the cell cycle between synchronized and unperturbed asynchronously growing human lymphocyte leukemia MOLT-4 cells. Here, we demonstrate that the sorted, asynchronously growing MOLT-4 cells had considerably lower levels of cyclins A, B1, D3 and E than their counterparts of the cells arrested in G1/S phase, as assessed by flow cytometry. In addition, we confirmed these results by using post-sorting Western blotting, a new method we recently developed for examining protein expression in specific phases of sorted, synchronized or asynchronously growing cells. Our findings revealed that the levels of cyclins D3 and E in the asynchronously growing MOLT-4 cells were significantly lower than those in synchronized cultures. Interestingly, protein expression levels of cyclins A and B1 in the asynchronously growing MOLT-4 cells were barely measurable, suggesting that these proteins were either not expressed or under detectable levels. These studies indicate that our synchronization protocol may have disturbed cell proliferation and metabolism as evidenced by significant differences in the expression of cyclins between asynchronously growing and synchronized cells, and further suggest that the levels of cyclins A, B1, D3 and E in synchronized cultures cannot represent those in unperturbed, asynchronously growing cells. Thus, it appears that thymidine-treated, synchronized cells may not be suitable experimental models for the study of normal cell cycle.

Blotting, Western↗

PubMed2004

Modelling strategies for controlling SARS outbreaks.

Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.

Computer Simulation↗

PubMed2004

Critical delay for overshooting in planned arm movements with delayed feedback.

The Vector Integration To Endpoint (VITE) circuit describes a real time neural network model which simulates behavioral and neurobiological properties of planned arm movements by the interaction of two populations of neurons. This model is generalized to include delay between the interacting populations, which is found to have a detrimental effect on movement accuracy. Conditions are given on the model parameters for accurate movement and target overshoot, where we show that there exists a non-zero critical value of the delay which the circuit can support while maintaining accurate movement. This critical delay depends on the movement speed, and becomes arbitrarily large for sufficiently slow movement. Thus neurobiological or artificial systems modelled by the VITE sensory-motor loop can tolerate an arbitrarily large delay if the movement speed is sufficiently slow.

Arm↗

PubMed2004

New method for the analysis of cell cycle-specific apoptosis.

BACKGROUND: In this study, a new method for the analysis of cell cycle specificity of apoptosis was designed by using a modified annexin V and propidium iodide (API) method. METHODS: Cells of the human promyelocytic HL-60 line treated with camptothecin (CPT) or ultraviolet light (UV) were labeled with fluorescein isothiocyanate-conjugated annexin V and prefixed with 1% methanol-free formaldehyde on ice, and their DNA was stained stoichiometrically with propidium iodide in the presence of digitonin. Cellular green and red fluorescences were measured by flow cytometry. RESULTS: Cell cycle specificity of apoptosis obtained by the API method and those analyzed for the presence of DNA strand breaks by using terminal deoxynucleotidyl transferase (TdT) assay were similar: CPT- or UV-induced apoptosis preferentially in S- or G1-phase cells, respectively. When the internucleosomal DNA degradation was prevented by the serine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone, apoptotic cells could not be detected by the TdT assay but were identified by the API method. CONCLUSIONS: The API method, similar to the TdT assay, accurately detects the cell cycle phase specificity of apoptosis. Also, the API method appears to detect earlier stages of apoptosis than the TdT assay.

Annexin A5↗

PubMed2004

Dynamics of projective adaptive resonance theory model: the foundation of PART algorithm.

Projective adaptive resonance theory (PART) neural network developed by Cao and Wu recently has been shown to be very effective in clustering data sets in high dimensional spaces. The PART algorithm is based on the assumptions that the model equations of PART (a large scale and singularly perturbed system of differential equations coupled with a reset mechanism) have quite regular computational performance. This paper provides a rigorous proof of these regular dynamics of the PART model when the signal functions are special step functions, and provides additional simulation results to illustrate the computational performance of PART.

Algorithms↗

PubMed2002

Projective ART for clustering data sets in high dimensional spaces.

A new neural network architecture (PART) and the resulting algorithm are proposed to find projected clusters for data sets in high dimensional spaces. The architecture is based on the well known ART developed by Carpenter and Grossberg, and a major modification (selective output signaling) is provided in order to deal with the inherent sparsity in the full space of the data points from many data-mining applications. This selective output signaling mechanism allows the signal generated in a node in the input layer to be transmitted to a node in the clustering layer only when the signal is similar to the top-down weight between the two nodes and, hence, PART focuses on dimensions where information can be found. Illustrative examples are provided, simulations on high dimensional synthetic data and comparisons with Fuzzy ART module and PROCLUS are also reported.

Algorithms↗

PubMed2002

[Change of immunosuppressive acidic protein in sera of patients with pulmonary tuberculosis and its clinical significance].

OBJECTIVE: To investigate the change of immunosuppressive acidic protein (IAP) in sera of patients with pulmonary tuberculosis (TB) and its clinical value. METHOD: IAP in sera of 336 patients suffering from pulmonary TB and controls was detected by agar diffusion assay. RESULTS: In pulmonary TB, healthy controls and non-TB respiratory diseases, the level of IAP was (797 +/- 168) mg/L, (367 +/- 71) mg/L and (404 +/- 75) mg/L, respectively. If > 500 mg/L was regarded as positive threshold, the positive rates in the above groups were 96.7%, 9.2% and 9.6%, respectively. IAP positive rates in cases of primary, disseminated, infiltrative, chronic fibro-cavernous pulmonary TB and tuberculous pleuritis were 100, 0%, 100.0%, 96.0%, 98.6% and 96.9%, respectively. IAP was significantly higher in progressive pulmonary TB than in stable pulmonary TB, and was decreased when patients' condition improved after treatment. CONCLUSION: Detection of IAP in sera of patients with pulmonary TB can reflect patients' immunosuppression status and the severity of the disease, and may be useful in assessing treatment effect and evaluating prognosis.

Humans↗