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Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.
Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage
Development of improved inhibitors of wall teichoic acid biosynthesis with potent activity against Staphylococcus aureus
A small molecule (1835F03) that inhibits Staphylococcus aureus wall teichoic acid biosynthesis, a proposed antibiotic target, has been discovered. Rapid, parallel, solution-phase synthesis was employed to generate a focused library of analogs, providing detailed information about structure–activity relationships and leading to the identification of targocil, a potent antibiotic
Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients
Peer reviewedPublisher PD
Short-term prospective memory deficits in chronic back pain patients
Objective: Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time.
Methods: The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering.
Results: In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs.
Conclusions: These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given
HOME RANGES OF THE NILGAI ANTELOPE (\u3ci\u3eBOSELAPHUS TRAGOCAMELUS\u3c/i\u3e) IN TEXAS
Information related to home ranges of the nilgai antelope (Boselaphus tragocamelus) was needed to estimate spread of cattle-fever ticks (Riphicephalus microplus and R. annulatus) and to develop management protocols. We captured, placed telemetry collars on, and monitored 10 male and 12 female nilgai antelopes during February 2006–May 2008. We detected no difference between size of home ranges of males and females and determined maximum axes of home ranges of 16.3 and 13.8 km, respectively. The combination of large home ranges and large axes of home range indicates that if cattle-fever ticks are being maintained on nilgai antelopes, then the area in which these antelopes may spread ticks is great
HOME RANGES OF THE NILGAI ANTELOPE (\u3ci\u3eBOSELAPHUS TRAGOCAMELUS\u3c/i\u3e) IN TEXAS
Information related to home ranges of the nilgai antelope (Boselaphus tragocamelus) was needed to estimate spread of cattle-fever ticks (Riphicephalus microplus and R. annulatus) and to develop management protocols. We captured, placed telemetry collars on, and monitored 10 male and 12 female nilgai antelopes during February 2006–May 2008. We detected no difference between size of home ranges of males and females and determined maximum axes of home ranges of 16.3 and 13.8 km, respectively. The combination of large home ranges and large axes of home range indicates that if cattle-fever ticks are being maintained on nilgai antelopes, then the area in which these antelopes may spread ticks is great
Tumour inflammatory infiltrate predicts survival following curative resection for node-negative colorectal cancer
<b>Background</b>: A pronounced tumour inflammatory infiltrate is known to confer a good outcome in colorectal cancer. Klintrup and colleagues reported a structured assessment of the inflammatory reaction at the invasive margin scoring low grade or high grade. The aim of the present study was to examine the prognostic value of tumour inflammatory infiltrate in node-negative colorectal cancer.
<b>Methods</b>: Two hundred patients had undergone surgery for node-negative colorectal cancer between 1997 and 2004. Specimens were scored with Jass’ and Klintrup’s criteria for peritumoural infiltrate. Pathological data were taken from the reports at that time.
<b>Results</b>: Low-grade inflammatory infiltrate assessed using Klintrup’s criteria was an independent prognostic factor in node-negative disease. In patients with a low-risk Petersen Index (n = 179), low-grade infiltrate carried a threefold increased risk of cancer death. Low-grade infiltrate was related to increasing T stage and an infiltrating margin.
<b>Conclusion</b>: Assessment of inflammatory infiltrate using Klintrup’s criteria provides independent prognostic information on node-negative colorectal cancer. A high-grade local inflammatory response may represent effective host immune responses impeding tumour growth
Marked Campylobacteriosis Decline after Interventions Aimed at Poultry, New Zealand
A population-level food safety response successfully reduced disease incidence
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