Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Except for a small fraction of persisters, 10(-6) to 10(-5), Escherichia coli K-12 is killed by prolonged inhibition of murein synthesis. The progeny of persisters are neither more resistant to inhibition of murein synthesis nor more likely to persist than normal cells. Mutants have been isolated in which a larger fraction, 10(-2), persists. The persistent response of the mutants, Hip (high persistence), is to inhibition of murein synthesis at early or late steps by antibiotics (phosphomycin, cycloserine, and ampicillin) or by metabolic block (starvation for diaminopimelic acid). Killing of the parent strain by each of the four inhibitors has two phases: The first is rapid and lasts about 30 min; the second is slower, but still substantial, and lasts 3 to 4 h. The first phase also occurs in the Hip mutants, but then viability of the mutants remains constant after about 30 min. Neither tolerance, resistance, impaired growth, nor reversion of spheroplasts accounts for high-frequency persistence. Two of the mutations map at 33.8 min in a region containing few other recognized functions. This position and the phenotypes define hipA as a newly recognized gene. Transposons Tn5 and Tn10 have been inserted close to hipA making it possible to explore the molecular genetics of persistence, a long recognized but poorly understood phenomenon.
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PMID:hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. 634 26

A novel design of polyurethane compliant layer acetabular cup has been developed through a series of friction, creep and wear tests. Friction tests were initially conducted on ABG standard form, polyurethane acetabular cups and an ABG standard form, UHMWPE acetabular cup for comparison. The polyurethane cups showed lower friction than the UHMWPE cup with maximum friction factors between 0. 008 and 0.02 compared with 0.035 for the UHMWPE cup. This indicated that, in the polyurethane cups, more of the load across the joint was carried by the fluid entrapped in the joint space rather than with asperity contact, compared with the UHMWPE cup. The inherent compliance of the polyurethane is used to promote elasto-hydrodynamic lubrication. However, this compliance raised concerns over excessive creep, which may in turn adversely affect tribological performance. Therefore, creep tests were undertaken on the ABG standard form, polyurethane acetabular cups followed by further friction tests. Small amounts of creep occurred in the polyurethane cups at ambient temperature, which reduced the friction slightly (maximum friction factors of 0.009) due to increased conformity between the head and the cup. However, at 37 degrees C, greater creep occurred causing pinching of the femoral head by the acetabular cup resulting in lubricant starvation and higher friction (maximum friction factors of 0.035). The design of the polyurethane cups was subsequently modified to incorporate a flared rim to eliminate the possibility of fluid starvation through pinching. Creep in polyurethane acetabular cups is also affected by the method of fixation of the cups, due to the conformity with and the stiffness of the cup backing. Hence, a one-million-cycle wear test was performed on five ABG flared form, polyurethane acetabular cups on the Mk. I Durham Hip Joint Wear Simulator to evaluate the best method of fixation for the polyurethane cups. The smallest amount of penetration, due to creep and wear, was found with cement fixation (0.30 mm penetration with cement fixation, 0.44 mm with polyethylene holder mounting, and 0.52 mm with metal shell mounting). A 4. 25-million-cycle wear test was then conducted on a further five ABG flared form, polyurethane acetabular cups with cement fixation. Five ABG standard form, UHMWPE acetabular cups were also wear-tested to 5. 0-million cycles. The mean and standard error of the wear rate for the polyurethane cups were 14.1 +/- 4.3 mg/10(6) (12.0 +/- 3.6 mm(3)/10(6)), cycles compared with 44.8 +/- 3.4 mg/10(6) (48.2 +/- 3. 7 mm(3)/10(6)), cycles for the UHMWPE cups. This study showed that the novel polyurethane-compliant layer acetabular cup with cement fixation was tribologically superior to the ABG standard form UHMWPE design currently being used clinically.
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PMID:A tribological study of UHMWPE acetabular cups and polyurethane compliant layer acetabular cups. 1107 31

Tumor suppressor protein p53 aggregates in the hypoxic core of solid tumors. C terminus of Hsc70-interacting protein (CHIP) displays chaperone as well as E3 ligase activities in both stabilizing and degrading wild-type and mutant p53. In this study, we have discovered that CHIP selectively degrades aggregating mutant p53 under both normal and hypoxic conditions. Silencing of CHIP alleviates degradation of aggregating mutant p53 in both normoxia and hypoxia, but has no significant effect on the level of nonaggregating mutant p53. Although both U-box and TPR domains of CHIP are responsible for p53 degradation, the U-box domain selectively binds to aggregating mutant p53, whereas the TPR domain interacts with nonaggregating mutant p53. The degradation of mutant p53 by CHIP is shown to be via autophagy through K63-linked polyubiquitination. Both in normoxia and under physiological hypoxia, the level of aggregating mutant p53 in the presence of CHIP was reduced threefold, whereas under serum starvation, it was reduced fivefold. Interestingly, both wild-type and mutant p53 interact with and stabilize CHIP at the post-translational level, suggesting a chaperone synergy between p53 and CHIP. This finding may have strong therapeutic significance via selective degradation of oncogenic mutant p53 in regressing hypoxic tumors.
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PMID:CHIP promotes autophagy-mediated degradation of aggregating mutant p53 in hypoxic conditions. 2995 28