The nuclear oxysterol receptors liver X receptor-alpha LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regulate genes involved in cholesterol homeostasis. Although both LXR subtypes are expressed ...in the brain, their roles in this tissue remain largely unexplored. In this report, we show that LXR agonists have marked effects on gene expression in murine brain tissue both in vitro and in vivo. In primary astrocyte cultures, LXR agonists regulated several established LXR target genes, including ATP binding cassette transporter A1, and enhanced cholesterol efflux. In contrast, little or no effect on gene expression or cholesterol efflux was detected in primary neuronal cultures. Treatment of mice with a selective LXR agonist resulted in the induction of several LXR target genes related to cholesterol homeostasis in the cerebellum and hippocampus. These data provide the first evidence that the LXRs regulate cholesterol homeostasis in the central nervous system. Because dysregulation of cholesterol balance is implicated in central nervous system diseases such as Alzheimer's and Niemann-Pick disease, pharmacological manipulation of the LXRs may prove beneficial in the treatment of these disorders.
Antisense RNA is a versatile tool for reducing gene expression. It was used to determine if ahpC, a gene that is involved in defence against oxidative stress and isoniazid (INH) resistance, is ...important for virulence of Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex. Antisense RNA constructs of ahpC were made using different strength promoters in front of a reversed coding sequence of ahpC. These constructs were electroporated into a virulent wild-type M. bovis strain and a moderately virulent INH-resistant M. bovis strain that was catalase/peroxidase-negative. Down-regulation of protein synthesis occurred and this was visualized by immunoblotting. All strains containing antisense RNA were markedly less virulent than their parent strains in guinea pigs. M. bovis with an up-regulated ahpC gene was more resistant to cumene hydroperoxide than its parent strain, which had a wild-type ahpC promoter. These results agree with a model of INH resistance in which overexpression of AhpC compensates in some INH-resistant strains for loss of catalase/peroxidase by maintaining the ability to defend against oxidative stress mediated through organic peroxides. In addition, normal expression of AhpC is crucial for maintaining the virulence of wild-type M. bovis, which has normal catalase/peroxidase levels.
A rice (Oryza sativa L.) crop functions as a population of tillers produced at different times and possessing specific growth characteristics. The objective of this study was to characterize the ...contribution of cultivar tillering ability to dry matter accumulation, yield components, and grain yield. Field experiments were conducted over a 2‐yr period using a completely randomized plot design at Beaumont, TX, grown under a pin‐point flood system, with a China clay soil (fine, smectitic, hyperthermic Oxyaquic Dystrudert). Three cultivars were chosen (Gulfmont, Rosemont, and Teqing), to represent moderate to high tillering abilities, and three plant densities were chosen (56, 112, and 169 plants m−2), to produce differential competition for light and nutrients. Teqing had the highest tillering ability and partitioned more mass to tillers, especially at the lowest plant density, with 77% of the total mass represented by tillers, compared with 71 and 69% for Gulfmont and Rosemont, respectively. However, total dry mass per unit area at harvest was not significantly different, contrasting the plant density treatments (1618, 1725, and 1744 g m−2 for the 56, 112, and 169 plants m−2 treatments, respectively, when averaged across cultivars). Both cultivar and plant density significantly affected a number of yield components, but not kernel weight. The higher yield of Teqing (918 g m−2), contrasted with the lower‐yielding Gulfmont (791 g m−2) and Rosemont (729 g m−2), appears largely to have resulted from its greater tillering ability, higher spikelet density, and longer maturation period, which makes greater use of the relatively long growing season length at Beaumont.
The improved characterisation of risk factors for rheumatoid arthritis (RA) suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be ...evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA). Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs) and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA)-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls); UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls). HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC) value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG). Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001); ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively.
Objective To examine the effect of bladder infusion before catheter removal on patients' readiness for discharge and the day of discharge after transurethral resection of the prostate (TURP).
...Patients and methods The study comprised 75 consecutive patients undergoing TURP who were randomized to either have their catheter removed in the standard manner (38 patients), or to undergo bladder infusion before a trial of voiding (ToV) on the second day after TURP (37 patients).
Results In those undergoing bladder infusion, seven (19%) patients were discharged on the same day as their ToV, compared with five (13%) in the standard group. Of the 75 patients, 15 (68%) were discharged by the third day after TURP whether or not the bladder had been filled. In the infusion group, 23 (62%) were ready for discharge on the same day as their TOV, compared with only 14 (37%) in the standard group (P < 0.05).
Conclusion Bladder infusion before a ToV after TURP significantly increases the rate of readiness for discharge, allowing an early decision to discharge on the second day in a large proportion of patients.
The MICs of 13 antimicrobial agents including seven fluoroquinolones (ciprofloxacin, levofloxacin, sparfloxacin, grepafloxacin, gatifloxacin, moxifloxacin and clinafloxacin) for Streptococcus ...pneumoniae isolates obtained from all regions of Hong Kong in the year 2000 were determined by the Etest. Overall, 39.4% of 180 isolates were susceptible to penicillin, 11.7% were intermediate and 48.9% were resistant. The overall prevalence of fluoroquinolone non-susceptibility (levofloxacin MIC 4 mg/L) was 13.3% but increased to 27.3% among the penicillin-resistant isolates. For the fluoroquinolone non-susceptible isolates, within-class cross-resistance was common. For the fluoroquinolone non-susceptible isolates, the median MICs of clinafloxacin, gatifloxacin, moxifloxacin, sparfloxacin and grepafloxacin were, respectively, six-, 24-, 32- 84- and 128-fold higher than those for the susceptible isolates. All fluoroquinolone non-susceptible strains were derived from adults. The prevalence of fluoroquinolone resistance was higher in isolates from older patients (17.1% among those 65 years of age versus 9.1% among those 18–64 years of age, P < 0.001) and from adults with chronic obstructive pulmonary disease (24.6% versus 9.3%, P = 0.01). All fluoroquinolone non-susceptible strains were non-susceptible to penicillin (MIC range 2–4 mg/L), cefotaxime (MIC range 1–4 mg/L) and erythromycin (MIC range 4–256 mg/L). The fluoroquinolone non-susceptible isolates were genetically related to the Spain23F-1 clone when analysed by pulse-field gel electrophoresis and multilocus sequence typing. In conclusion, a rapid increase in the prevalence of fluoroquinolone resistance among S. pneumoniae was found in Hong Kong. Typing analysis suggests that this is due to the pan-regional dissemination of a fluoroquinolone-resistant variant (designated Hong Kong23F-1) of the globally distributed Spain23F-1 clone.
The DIRC particle identification system for the BaBar experiment Aleksan, R.; Amerman, L.; Aston, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2005, Volume:
538, Issue:
1-3
Journal Article
Peer reviewed
Open access
A new type of ring-imaging Cherenkov detector is being used for hadronic particle identification in the BABAR experiment at the SLAC B Factory (PEP-II). This detector is called DIRC, an acronym for ...Detection of Internally Reflected Cherenkov (Light). This paper will discuss the construction, operation and performance of the BABAR DIRC in detail.
Here, we present evidence for the exotic charged charmoniumlike state Z±c(3900) decaying to J/ψπ± in semi-inclusive weak decays of b-flavored hadrons. The signal is correlated with a parent J/ψπ+π- ...system in the invariant-mass range 4.2–4.7 GeV that would include the exotic structure Y(4260). The study is based on 10.4 fb-1 of pp¯ collision data collected by the D0 experiment at the Fermilab Tevatron collider.
DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to ...date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.
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