The impact of lagging strand replication mutations on the stability of CAG repeat tracts in yeast

We have examined the stability of long tracts of CAG repeats in yeast mutants defective in enzymes suspected to be involved in lagging strand replication. Alleles of DNA ligase (cdc9-1 and cdc9-2) destabilize CAG tracts in the stable tract orientation, i.e., when CAG serves as the lagging strand template. In this orientation nearly two-thirds of the events recorded in the cdc9-1 mutant were tract expansions. While neither DNA ligase allele significantly increases the frequency of tract-length changes in the unstable orientation, the cdc9-1 mutant produced a significant number of expansions in tracts of this orientation. A mutation in primase (pri2-1) destabilizes tracts in both the stable and the unstable orientations. Mutations in a DNA helicase/deoxyribonuclease (dna2-1) or in two RNase H activities (rnh1Delta and rnh35Delta) do not have a significant effect on CAG repeat tract stability. We interpret our results in terms of the steps of replication that are likely to lead to expansion and to contraction of CAG repeat tracts.     

Endoscopic approach for the resection of forehead masses

Over the past several years, surgery aided by the endoscope has come into favor for a number of reasons. Because it is minimally invasive surgery, it has less morbidity, thus, reduced postoperative pain and complications. It results in earlier mobilization and shorter hospitalization, and most importantly, it contributes to an improved cosmetic appearance as a result of a shortened incision line concealed within the hairline in most cases. We have proposed an alternative approach to the surgical resection of forehead masses by means of the endoscope, which has proven to be useful not only for diagnosis but also as a therapeutic tool for the removal of forehead lesions. This report described the clinical experience with the removal of forehead masses in four patients. The cases illustrated the feasibility and ease of resecting a variety of forehead masses with excellent cosmetic results. We hope that more plastic surgeons will use the proposed technique and will continue to explore the safe limits of endoscopic plastic surgery.     

556例多发伤患者的急诊救治临床分析

目的探讨多发伤患者的救治策略。方法回顾分析我科2000年1月至2008年5月急诊抢救的556例多发伤患者的临床资料。结果 16例患者经抢救无效死亡,死亡率2.88%;其余患者均经紧急抢救及行必要实验室检查,病情稳定,好转率达97.12%。平均抢救时间为(1.37±1.05)h。结论强化多发伤的急诊科早期救治,树立创伤急救"黄金1 h"观念,是提高多发伤患者生存率及降低死亡率的关键。     

Altruism,tit for tat and ‘outlaw’ genes

Summary In a prior study we combined game theory and inclusive fitness models to examine whether the guarded altruism that can evolve among non-relatives (tit for tat, TFT) might also evolve among close relatives, supplanting unconditional altruism. In most cases, TFT replaced unconditional altruism in family-structured models. Even when TFT is selected at a single locus, however, by withholding altruism from non-reciprocating relatives it may qualify as an outlaw from the standpoint of modifier genes at other loci. Here we examine this possibility with a series of haploid, two-locus models in which a modifier gene transforms TFT into unconditional altruism. The modifier allele spreads to fixation whenever Hamilton's Rule is satisfied, resulting in an unconditional altruist replacing the TFT strategy. As such, TFT may be regarded as an outlaw vulnerable to suppression by alleles at other loci.     

A novel method for characterisation of microbial growth kinetics on volatile organic compounds

A novel method for the determination of microbial growth kinetics on hydrophobic volatile organic compounds (VOC) has been developed. A stirred tank reactor was operated as a fed-batch system to which the VOC was continuously fed via the gas phase, assuring a constant VOC concentration in the mineral medium. A flow of air was saturated with the VOC, and then mixed with a further flow of air, to obtain a predetermined VOC concentration. Thus, different VOC concentrations in the mineral medium could be obtained by altering the VOC concentration in the feed gas. The growth kinetics of Xanthobacter autotrophicus GJ10 on 1,2-dichloroethane (DCE) and of Pseudomonas sp. strain JS150 on MonoChloroBenzene (MCB) were assessed using this method. The growth of strain JS150 was strongly inhibited at MCB concentrations higher than 160 mg l⁻¹, and the results were fitted using a piecewise function. The growth kinetics of strain GJ10 were described by the Luong model where maximum growth rate μ_max = 0.12 h⁻¹, substrate saturation constant K _S = 7.8 mg l⁻¹, and maximum substrate concentration S _m (above which growth is completely inhibited) = 1080 mg l⁻¹. Varying nitrogen and oxygen flows enabled the effect of oxygen concentration on the growth kinetics of Pseudomonas JS150 to be determined. Received: 30 November 1998 / Received revision: 19 March 1999 / Accepted: 20 March 1999     

Apoplastic Sugars, Fructans, Fructan Exohydrolase, and Invertase in Winter Oat: Responses to Second-Phase Cold Hardening

Changes in apoplastic carbohydrate concentrations and activities of carbohydrate-degrading enzymes were determined in crown tissues of oat (Avena sativa L., cv Wintok) during cold hardening. During second-phase hardening (−3°C for 3 d) levels of fructan, sucrose, glucose, and fructose in the apoplast increased significantly above that in nonhardened and first-phase-hardened plants. The extent of the increase in apoplastic fructan during second-phase hardening varied with the degree of fructan polymerization (DP) (e.g. DP3 and DP4 increased to a greater extent than DP7 and DP > 7). Activities of invertase and fructan exohydrolase in the crown apoplast increased approximately 4-fold over nonhardened and first-phase-hardened plants. Apoplastic fluid extracted from nonhardened, first-phase-hardened, and second-phase-hardened crown tissues had low levels, of symplastic contamination, as determined by malate dehydrogenase activity. The significance of these results in relation to increases in freezing tolerance from second-phase hardening is discussed.     

A polyvalent vaccine for high-risk prostate patients: “are more antigens better?”

We have shown the immunogenicity and safety of synthetic carbohydrate vaccines when conjugated to the carrier keyhole limpet hemocyanin (KLH) and given with the adjuvant, QS-21, in patients with biochemically relapsed prostate cancer. To determine whether immune response could be further enhanced with stimulation by multiple antigens, a hexavalent vaccine was prepared using previously determined doses and administered in a Phase II setting to 30 high-risk patients. The hexavalent vaccine included GM2, Globo H, Lewis^y, glycosylated MUC-1-32mer and Tn and TF in a clustered formation, conjugated to KLH and mixed with QS-21. Eight vaccinations were administered over 13 months. All 30 patients had significant elevations in antibody titers to at least two of the six antigens; 22 patients had increased reactivity with FACS. These serologic responses were lower than that seen previously in patients treated with the respective monovalent vaccines. The reciprocal median combined IgM and IgG antibody titers with ELISA against MUC1, Tn, TF, globo H and GM2 for these 30 patients were 640, 80, 120, 40 and 0, compared to 1280, 640, 1280, 320 and 160 seen in patients receiving individual monovalent vaccines. This hexavalent vaccine of synthetic “self” antigens broke immunologic tolerance against two or more antigens in all 30 vaccinated patients, was safe, but antibody titers against several of the antigens were lower than those seen in individual monovalent trials. No impact on PSA slope was detected. We address the relevance of the multivalent approach for prostate cancer treatment. Supported by the Prostate Cancer Foundation, The PepsiCo Foundation, The Sharon Hels and Brad Reed Fund, Swim Across America, The Sara Chait Foundation. Dr. Philip Livingston is a consultant for and shareholder in Progenics Pharmaceuticals, Inc.