573 research outputs found
Cyclin F Is Degraded during G2-M by Mechanisms Fundamentally Different from Other Cyclins
Cyclin F, a cyclin that can form SCF complexes and bind to cyclin B, oscillates in the cell cycle with a pattern similar to cyclin A and cyclin B. Ectopic expression of cyclin F arrests the cell cycle in G2/M. How the level of cyclin F is regulated during the cell cycle is completely obscure. Here we show that, similar to cyclin A, cyclin F is degraded when the spindle assembly checkpoint is activated and accumulates when the DNA damage checkpoint is activated. Cyclin F is a very unstable protein throughout much of the cell cycle. Unlike other cyclins, degradation of cyclin F is independent of ubiquitination and proteasome-mediated pathways. Interestingly, proteolysis of cyclin F is likely to involve metalloproteases. Rapid destruction of cyclin F does not require the N-terminal F-box motif but requires the COOH-terminal PEST sequences. The PEST region alone is sufficient to interfere with the degradation of cyclin F and confer instability when fused to cyclin A. These data show that although cyclin F is degraded at similar time as the mitotic cyclins, the underlying mechanisms are entirely distinct
A Model to Induce Low Temperature Trauma for in vitro Astrogliosis Study*
Astrogliosis is an inevitable and rapid response of astrocytes to physical, chemical and pathological injuries. To study astrogliosis, we developed a reproducible in vitro model in which low temperature injury to cultured astrocytes could be induced by placing the culture dish onto a copper pipe pre-cooled by liquid nitrogen. Using this model, the relationship between the temperature decline and the severity of cellular damage was analyzed. An increase in the expression of some known injury-related proteins, such as glial fibrillary acidic protein (GFAP), immediate early response genes (IEGs), and heat shock proteins 70 (HSP70), was demonstrated in astrocytes after low temperature trauma. With the use of this low temperature trauma model, the flexibility in the temperature control and injury area may allow researchers to evaluate cryotherapy and cryosurgery, which could be applicable to future development of quality health care
An expert consensus for the management of chronic hepatitis B in Asian Americans.
BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide.
AIM: To generate recommendations for the management of Asian Americans infected with HBV.
METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women.
RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10
CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes
Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142904/1/hep29800.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142904/2/hep29800_am.pd
Enhanced Secondary Electron Emission from Group III Nitride/ZnO Coaxial Nanorod Heterostructures
Needle work: AlN/ZnO and GaN/ZnO coaxial nanoneedle heterostructures (see TEM image) have a higher secondary electron emission (SEE) yield () than thin films of AlN and GaN deposited on Si substrates. The dependence of the SEE on the incidence angle of the beam indicates that these heterostructures do not follow the power law. The value of the heterostructures is enhanced by the inherited nanostructure from the ZnO nanoneedle template.This work was supported by NTU RGM 17/04, the National Creative Research Initiative Project, and the Center for Nanostructured Materials Technology under the 21st Century Frontier R&D Program of the Ministry of Science and Technology, Korea
Evaluation of the performance of a modified Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system for critically ill patients in emergency departments in Hong Kong
Introduction
Numerous prognostic predictive models have been developed for critically ill patients, many of which are primarily designed for use in intensive care units. The objective of this study was to evaluate the accuracy of a modified Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in predicting the mortality for critically ill patients managed in emergency department (ED) resuscitation rooms in Hong Kong.
Method
A multi-centre, prospective study was conducted for patients managed in the resuscitation rooms of the EDs of four major hospitals, including one university teaching hospital. The primary outcome measure was 14 day all-cause mortality and the secondary outcome measure was the length of stay in hospital.
Results
Of 867 patients recruited between 4 and 30 April 2004, 106 (12.2%) patients died. The modified APACHE II score was found to be significantly higher in non-survivors compared to survivors (mean ± S.D.: 21.2 ± 7.7 versus 14.4 ± 7.1, p < 0.001). The area under the curve for modified APACHE II in predicting mortality was 0.743 (95% CI, 0.696–0.790).
Conclusion
The modified APACHE II score is only a moderate predictor of mortality for critically ill patients managed in the resuscitation rooms of EDs in Hong Kong. A more ED specific scoring method is required
DNA Damage during the Spindle-Assembly Checkpoint Degrades CDC25A, Inhibits Cyclin–CDC2 Complexes, and Reverses Cells to Interphase
Cell cycle checkpoints that monitor DNA damage and spindle assembly are essential for the maintenance of genetic integrity, and drugs that target these checkpoints are important chemotherapeutic agents. We have examined how cells respond to DNA damage while the spindle-assembly checkpoint is activated. Single cell electrophoresis and phosphorylation of histone H2AX indicated that several chemotherapeutic agents could induce DNA damage during mitotic block. DNA damage during mitotic block triggered CDC2 inactivation, histone H3 dephosphorylation, and chromosome decondensation. Cells did not progress into G(1) but seemed to retract to a G(2)-like state containing 4N DNA content, with stabilized cyclin A and cyclin B1 binding to Thr14/Tyr15-phosphorylated CDC2. The loss of mitotic cells was not due to cell death because there was no discernible effect on caspase-3 activation, DNA fragmentation, or viability. Extensive DNA damage during mitotic block inactivated cyclin B1-CDC2 and prevented G(1) entry when the block was removed. The mitotic DNA damage responses were independent of p53 and pRb, but they were dependent on ATM. CDC25A that accumulated during mitosis was rapidly destroyed after DNA damage in an ATM-dependent manner. Ectopic expression of CDC25A or nonphosphorylatable CDC2 effectively inhibited the dephosphorylation of histone H3 after DNA damage. Hence, although spindle disruption and DNA damage provide conflicting signals to regulate CDC2, the negative regulation by the DNA damage checkpoint could overcome the positive regulation by the spindle-assembly checkpoint
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