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Biomedical subjects

Ge Wu

Publications and source records attributed to Ge Wu.

17 recordsLinked to original sources
PubMed2024

One-pot Golden Gate Assembly of an avian infectious bronchitis virus reverse genetics system.

Avian infectious bronchitis is an acute respiratory disease of poultry of particular concern for global food security. Investigation of infectious bronchitis virus (IBV), the causative agent of avian infectious bronchitis, via reverse genetics enables deeper understanding of virus biology and a rapid response to emerging variants. Classic methods of reverse genetics for IBV can be time consuming, rely on recombination for the introduction of mutations, and, depending on the system, can be subject to genome instability and unreliable success rates. In this study, we have applied data-optimized Golden Gate Assembly design to create a rapidly executable, flexible, and faithful reverse genetics system for IBV. The IBV genome was divided into 12 fragments at high-fidelity fusion site breakpoints. All fragments were synthetically produced and propagated in E. coli plasmids, amenable to standard molecular biology techniques for DNA manipulation. The assembly can be carried out in a single reaction, with the products used directly in subsequent viral rescue steps. We demonstrate the use of this system for generation of point mutants and gene replacements. This Golden Gate Assembly-based reverse genetics system will enable rapid response to emerging variants of IBV, particularly important to vaccine development for controlling spread within poultry populations.

Infectious bronchitis virus↗
PubMed2006

Coordinated regulation of AIB1 transcriptional activity by sumoylation and phosphorylation.

AIB1, a member of the steroid receptor coactivator (SRC) family that participates in gene transcriptional activation by nuclear receptors and other transcription factors, is required for animal growth and reproductive development and implicated in breast carcinogenesis. The mechanisms underlying the AIB1 pleiotropic functions are not fully understood and neither is the regulation of its activity. Here, we showed that AIB1 was a sumoylated protein and the sumoylation attenuated the transactivation activity of AIB1, which is in contrast to the sumoylation of its paralogs, GRIP1 and SRC-1. The transactivation activity of AIB1 is enhanced by its phosphorylation by several kinases, including mitogen-activated protein kinase. We demonstrated in this report that estrogen treatment led to an increased phosphorylation and decreased sumoylation of AIB1 and that the sumoylation coordinated with phosphorylation in regulating the transcriptional activity of AIB1, providing a mechanism for post-translational modifications in regulating the transcriptional output of AIB1.

Acetyltransferases↗
PubMed2006

A neural network approach to motor-sensory relations during postural disturbance.

This study explored whether artificial neural networks (ANN) can be used to quantify the motor-sensory relationship during postural disturbance. An ANN model was constructed with seven mechanical stimuli to the visual, vestibular and somatosensory systems (i.e., head angular and linear accelerations, eye-target distance, ankle joint rotation and velocity, as well as normal and shear ground contact forces under the feet) as inputs, and electromyographic activities of tibialis anterior and gastrocnemius muscles as outputs. These inputs and outputs were directly measured during a sudden toes-up-down rotation of the supporting base in two groups of elderly subjects: people with peripheral neuropathy (NP) who have severe loss of mechanoreception in the sole of their feet and people without NP. The products of ANN weights were used in a summary statistic called the Q-value to estimate the contribution of each mechanical stimulus to sensory systems in determining each leg muscle activity. It was found that: (1) the stimuli to the vestibular system and/or ankle proprioceptors have greater contributions to leg muscle activities, especially the TA muscle, in people with NP than people without NP; (2) the stimuli to somatosensory receptors have the greatest contribution, and the stimuli to the vestibular system have the least contribution to both muscle activities in both groups. These findings are supported by previous studies and have demonstrated the potential of the Q-value concept in the ANN model in studying the motor-sensory relationship in human postural control.

Aged↗
PubMed2006

HTS technologies in biopharmaceutical discovery.

The concepts and philosophies of HTS can be productively applied to the discovery of new biopharmaceuticals. It is now possible, comprehensively and systematically, to enumerate, clone, produce and screen all secreted proteins, by building upon knowledge accumulated over the past two decades in HTS, genomics and parallel protein expression technologies. Each of the crucial operational components (comprehensive and high-quality cDNA library construction, proper protein-sequence classification, high-throughput protein production, medically relevant assays, state-of-the-art screening and data management) must be optimized to increase the chances of success. In this review, we draw comparisons between small-molecule and protein screening to illuminate common underlying principles as well as differences between the two operations.

Animals↗
PubMed2006

Group tele-exercise for improving balance in elders.

This study was to assess the level of acceptance and efficacy of a group tele-exercise program designed for balance impaired elders to improve balance and reduce fear of falling. The program would allow a group of elderly subjects to participate in a structured, interactive, and supervised exercise class from their own homes through a videoconferencing system. A total of 17 independent living elderly subjects (mean age, 81 +/- 8 years) participated in the study. An Internet-based videoconferencing device (VCD) was installed in each subject's home, allowing real-time video and audio communication with the exercise instructor and all other participants. The exercise was in the form of Tai Chi Quan, three times per week for 15 weeks. The main study measures included exercise compliance, level of acceptance and satisfaction, and the effectiveness of the exercise program on balance, fear of falling, and general health. Three subjects dropped out of the study. For those remaining, the average compliance was 78% (range, 51% to 98%). All subjects were able to operate the VCD independently, and expressed earnest interest in continuing tele-exercise programs in the future. There were significant improvement (p < 0.05) postexercise in fear of falling score (18%), single leg stance time (43%), Up-and-Go time (21%), and body sway during quiet stance (>8%). This study has demonstrated that the group tele-exercise program is acceptable and welcomed by elders, and is effective for improving balance and reducing fear of falling.

Accidental Falls↗
PubMed2005

Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis.

Tamoxifen, a selective oestrogen receptor modulator, has been used in the treatment of all stages of hormone-responsive breast cancer. However, tamoxifen shows partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial cancer. The molecular explanation for these observations is not known. Here we show that tamoxifen and oestrogen have distinct but overlapping target gene profiles. Among the overlapping target genes, we identify a paired-box gene, PAX2, that is crucially involved in cell proliferation and carcinogenesis in the endometrium. Our experiments show that PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, and that this activation is associated with cancer-linked hypomethylation of the PAX2 promoter.

Animals↗
PubMed2005

Ground contact characteristics of Tai Chi gait.

BACKGROUND: To date, no direct measurement has been done that quantitatively characterizes the foot-ground contact during Tai Chi Chuan movements. The goal of this study was to quantify the biomechanical characteristics of foot-ground contact during a Tai Chi gait (TCG), one of the basic but common Tai Chi Chuan movements. METHODS: The ground reaction force profiles, center of pressure (COP) and plantar pressure patterns under the stance foot of TCG were directly measured in a sample of 10 healthy young individuals. RESULTS: The medial force reached a peak value of 12 +/- 2% body weight (BW) during early stance. The vertical force reached and maintained a peak value of 109 +/- 2% BW during single stance, and shifted within a range of 10% and 70% BW during double stance phases. There was a uniformly small rate of loading in all three directions throughout stance. The peak plantar pressure was fairly constant throughout stance in the rear-foot region (maximum value of 0.27 +/- 0.07 kPa/kg), but changed from 0 to 0.16 +/- 0.04 kPa/kg in the fore-foot region. The peak pressure difference between the fore-foot and rear-foot regions was less than 0.06 +/- 0.01 kPa/kg during single stance and the second double stance. The maximum plantar contact area during TCG was 60 +/- 9% of the foot area. The foot COP displaced largely during the early and late part of the stance and maintained fairly stationary during single stance. The maximum COP displacement in the medial-lateral direction was 64 +/- 8% of foot width. CONCLUSIONS: TCG had a low impact force, a fairly evenly distributed body weight between the fore-foot and rear-foot regions, and a large medial-lateral displacement of the foot COP.

Adult↗
PubMed2005

ISB recommendation on definitions of joint coordinate systems of various joints for the reporting of human joint motion--Part II: shoulder, elbow, wrist and hand.

In this communication, the Standardization and Terminology Committee (STC) of the International Society of Biomechanics proposes a definition of a joint coordinate system (JCS) for the shoulder, elbow, wrist, and hand. For each joint, a standard for the local axis system in each articulating segment or bone is generated. These axes then standardize the JCS. The STC is publishing these recommendations so as to encourage their use, to stimulate feedback and discussion, and to facilitate further revisions. Adopting these standards will lead to better communication among researchers and clinicians.

Anthropometry↗
PubMed2004

Molecular mechanisms involved in the growth stimulation of breast cancer cells by leptin.

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, an adipocyte-derived cytokine, elicits proliferative effects in some cell types and potentially stimulates the growth of mammary epithelium. Here we show that leptin induced time- and dose-dependent signal transducer and activator of transcription 3 (STAT3) phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 kinase activation in breast carcinoma cells. Blocking STAT3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation of MCF-7 cells, whereas blocking ERK1/2 activation by a specific ERK1/2 kinase inhibitor, U0126, did not result in any significant changes in leptin-induced cell proliferation. Our experiments also showed that one member of the p160 family of steroid receptor coactivators, steroid receptor coactivator (SRC)-1, but not glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), also functioned in gene transactivation in response to leptin treatment. Glutathione S-transferase pull-down experiments showed that SRC-1 physically interacted with the activation domain of STAT3 and that chromatin immunoprecipitation experiments detected the occupancy of SRC-1, but not GRIP1 or AIB1, on the promoter of STAT3 target genes. Our experiments collectively showed that SRC-1 is involved in STAT3 signaling pathway that is implicated in leptin-stimulated cell growth.

Breast Neoplasms↗
PubMed2004

Differential gene regulation by the SRC family of coactivators.

SRCs (steroid receptor coactivators) are required for nuclear receptor-mediated transcription and are also implicated in the transcription initiation by other transcription factors, such as STATs and NFkappaB. Despite phenotypic manifestations in gene knockout mice for SRC-1, GRIP1, and AIB1 of the SRC (Steroid Receptor Coactivator) family indicating their differential roles in animal physiology, there is no clear evidence, at the molecular level, to support a functional specificity for these proteins. We demonstrated in this report that two species of SRC coactivators, either as AIB1:GRIP1 or as AIB1:SRC-1 are recruited, possibly through heterodimerization, on the promoter of genes that contain a classical hormone responsive element (HRE). In contrast, on non-HRE-containing gene promoters, on which steroid receptors bind indirectly, either GRIP1 or SRC-1 is recruited as a monomer, depending on the cellular abundance of the protein. Typically, non-HRE-containing genes are early genes activated by steroid receptors, whereas HRE-containing genes are activated later. Our results also showed that SRC proteins contribute to the temporal regulation of gene transcription. In addition, our experiments revealed a positive correlation between AIB1/c-myc overexpression in ER+ breast carcinoma samples, suggesting a possible mechanism for AIB1 in breast cancer carcinogenesis.

Antigens, Neoplasm↗
PubMed2004

Spatial, temporal and muscle action patterns of Tai Chi gait.

This study was to quantitatively characterize the spatial, temporal, and neuromuscular activation patterns of Tai Chi gait (TCG). Ten healthy young subjects were tested. The kinematics of TCG and normal gait (NG) were measured using a marker-based motion analysis system and two biomechanical force plates. Surface electromyography (EMG) was recorded from six left-side muscles: tibialis anterior, soleus, peronaeus longus, rectus femoris, semitendinosus, and tensor fasciae latae. The results showed that TCG had (1) a longer cycle duration (11.9+/-2.4 vs. 1.3+/-0.2 s) and a longer duration of single-leg stance time (1.8+/-0.6 vs. 0.4+/-0.05 s); (2) a larger joint motion in ankle dorsi/plantar flexion (40+/-9 degrees vs. 20+/-8 degrees), knee flexion (82+/-8 degrees vs. 53+/-10 degrees), hip flexion (81+/-7 degrees vs. 24+/-4 degrees), and hip abduction (20+/-8 degrees vs. 0+/-3 degrees); (3) a larger lateral body shift (>25% vs. 5% body height); and (4) significant involvement of ankle dorsiflexors, knee extensors/hip flexors and hip abductors, as indicated by significantly higher peak (88+/-14%, 80+/-18% and 83+/-17% vs. 35+/-10%, 14+/-8% and 28+/-19% peak amplitude, respectively) and root-mean-square values of their EMG (37+/-6%, 32+/-7% and 33+/-7% vs. 23+/-7%, 11+/-8% and 22+/-11% peak amplitude, respectively), longer proportions of action (76+/-19%, 68+/-8% and 65+/-19% vs. 59+/-23%, 16+/-23% and 40+/-32% gait cycle duration, respectively), longer proportions of isometric and eccentric actions, and longer proportions of co-activations. These results demonstrate that the biomechanical characteristics of TCG can be quantified. The quantification of TCC movements is important for understanding its effect on balance, flexibility, strength, and health.

Adult↗
PubMed2003

Determining appropriate substrate conversion for enzymatic assays in high-throughput screening.

It is generally accepted that the conversion of substrate should be kept at less than 10% of the total substrate used when studying enzyme kinetics. However, 10% or less substrate conversion often will not produce sufficient signal changes required for robust high-throughput screening (HTS). To increase the signal-to-background ratio, HTS is often performed at higher than 10% substrate conversion. Because the consequences of high substrate conversion are poorly understood, the screening results are sometimes questioned by enzymologists. The quality of an assay is judged by the ability to detect an inhibitor under HTS conditions, which depends on the robustness of the primary detection signal (Z factor) and the sensitivity to an inhibitor. The assay sensitivity to an inhibitor is reflected in the observed IC(50) value or percent inhibition at a fixed compound concentration when single-point data are collected. The major concern for an enzymatic assay under high substrate conversion is that the sensitivity of the screen may be compromised. Here we derive the relationship between the IC(50) value for a given inhibitor and the percentage of substrate conversion using a first-order kinetic model under conditions that obey Henri-Michaelis-Menten kinetics. The derived theory was further verified experimentally with a cAMP-dependent protein kinase. This model provides guidance for assay developers to choose an appropriate substrate conversion in designing an enzymatic assay, balancing the needs for robust signal and sensitivity to inhibitors.

Catalysis↗
PubMed2003

Assay development and high-throughput screening of caspases in microfluidic format.

Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In addition, microfluidic screening and plate-based screening are compared in terms of reagent consumption, data quality, and ease of operation.

Caspase Inhibitors↗
PubMed2002

ISB recommendation on definitions of joint coordinate system of various joints for the reporting of human joint motion--part I: ankle, hip, and spine. International Society of Biomechanics.

The Standardization and Terminology Committee (STC) of the International Society of Biomechanics (ISB) proposes a general reporting standard for joint kinematics based on the Joint Coordinate System (JCS), first proposed by Grood and Suntay for the knee joint in 1983 (J. Biomech. Eng. 105 (1983) 136). There is currently a lack of standard for reporting joint motion in the field of biomechanics for human movement, and the JCS as proposed by Grood and Suntay has the advantage of reporting joint motions in clinically relevant terms. In this communication, the STC proposes definitions of JCS for the ankle, hip, and spine. Definitions for other joints (such as shoulder, elbow, hand and wrist, temporomandibular joint (TMJ), and whole body) will be reported in later parts of the series. The STC is publishing these recommendations so as to encourage their use, to stimulate feedback and discussion, and to facilitate further revisions. For each joint, a standard for the local axis system in each articulating bone is generated. These axes then standardize the JCS. Adopting these standards will lead to better communication among researchers and clinicians.

Biomechanical Phenomena↗
PubMed2002

Evaluation of the effectiveness of Tai Chi for improving balance and preventing falls in the older population--a review.

One of the challenges faced by people with advancing age is decreased postural stability and increased risks for falls. There has been an increased interest over the last decade in using Tai Chi as an intervention exercise for improving postural balance and preventing falls in older people. Despite the increased number of studies in recent years relating Tai Chi to balance and fall prevention, results are scattered and inconsistent. There is wide variation in the use of balance measures, subject population, type and duration of Tai Chi exercise, and type of study. This paper provides a systematic review/analysis of currently available study reports. The goal of the review is to address the following concerns: how the effect of Tai Chi on balance or fall prevention has been evaluated to date, what level of evidence exists supporting Tai Chi as an effective exercise for improving balance or preventing falls, and what factors could possibly affect the benefit of Tai Chi on balance or falls. This review also helps identify directions for future research.

Accidental Falls↗
PubMed2002

Improvement of isokinetic knee extensor strength and reduction of postural sway in the elderly from long-term Tai Chi exercise.

OBJECTIVES: To compare isokinetic strength of leg muscles and foot center of pressure (COP) as a measure of sway between long-term Tai Chi practitioners and controls. DESIGN: Cross-sectional study. SETTING: Community setting. PARTICIPANTS: Twenty subjects in the Tai Chi group and 19 subjects in the control group (age, >55 y). INTERVENTION: Subjects in Tai Chi group had practiced Tai Chi for a minimum of 3 years. MAIN OUTCOME MEASURES: Concentric and eccentric strength of knee extensors and flexors at 60 degrees/s and 120 degrees/s, and foot COP displacement during quiet stance with eyes open or closed. RESULTS: People in the Tai Chi group had significantly higher knee extensor strength at all speeds tested (P<.013), and smaller foot COP excursions for both eyes open and eyes closed conditions (P<.05) than people in control group. No significant difference existed in knee flexors between the 2 groups (P<.713). The COP excursions correlated significantly with the eccentric strength of knee extensors (P<.07) but not with the concentric strength of knee extensors (P<.14) or with the isokinetic strength of knee flexors at most of the speeds (P<.27). CONCLUSION: These findings support the hypothesis that the maintenance of eccentric strength of postural muscles in the lower extremities, which is beneficial for maintaining good postural stability, is helped through the long-term practice of Tai Chi.

Aged↗