Isolates and their potential use in complex gene mapping efforts

Linkage disequilibrium (LD), detectable with microsatellites in disease alleles over wide genetic intervals in population isolates, has facilitated mapping and positional cloning of numerous disease genes. We, among others, have shown that the LD intervals reach up to 1 Mb in general alleles of young subisolates, and that this feature most probably offers an avenue for the initial locus positioning for complex traits. Development of efficient SNP genotyping and characterization of haploblock structure of the human genome have introduced new prospects to LD-based fine mapping and haplotype-association studies. Encouraging associations have been reported for several complex diseases. Final breakthroughs in mapping of complex disease loci have emerged on large pedigrees in population isolates. Conversely, ignoring genealogical makeup of the study population seems to disclose false negative and false positive associations, directing resources down the drain.     

Analysis of outpatient surgery center safety using an internet-based quality improvement and peer review program

Assessing the quality of care delivered in office-based outpatient surgery centers is difficult because formerly there was no central data collection system. The American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF), in its ongoing effort to assess and improve patient care, has developed an Internet-based quality improvement and peer review program to analyze outcomes for surgery centers it accredits. Reporting is mandatory for all surgeons operating in AAAASF-accredited facilities. Each surgeon must report all unanticipated sequelae and at least six random cases reviewed by an accepted peer review group biannually. A total of 411,670 procedures were analyzed during a 2-year period (from 2001 to 2002). There were 2597 sequelae reported during this period. The most common sequela was hematoma formation following breast augmentation. Infection occurred in 388 cases. Deep vein thrombosis, pulmonary embolism, and intraoperative cardiac arrhythmias were found to occur in a frequency consistent with previous reports. Significant complications (hematoma, hypertensive episode, wound infection, sepsis, and hypotension) were infrequent. A total of 1378 significant sequelae were reported for 411,670 procedures. This calculates to one unanticipated sequela in 299 procedures (an incidence of 0.33 percent). Seven deaths were reported. A death occurred in one in 58,810 procedures (0.0017 percent). The overall risk of death was comparable whether the procedure was performed in an AAAASF-accredited office surgery facility or a hospital surgery facility.This study documents an excellent safety record for surgical procedures performed in accredited office surgery facilities by board-certified surgeons.     

转基因技术与大豆品质改良

大豆是重要的食用油、食用蛋白和饲用蛋白原料。应用转基因技术对调节大豆品质形成的关键基因进行定向操作,可大大加速优质大豆品种的选育进程,培育出适合不同消费需求的多样化优质大豆品种。文章主要综述了近年来转基因技术在大豆品质性状改良方面的应用进展,同时也简要介绍了目前已经发展起来的安全转基因技术。     

p-CPA enhances growth and quality of muskelon fruits

The effects of para-chlorophenoxyacetic acid(p-CPA) application in improving the reduction in growthrate and sugar accumulation, and on the peel color and firmness ofparthenocarpic fruit, and its residual content in the treated fruit wereexamined. p-CPA application to parthenocarpic fruit duringthe rapid growth stage [5 or 10 days after anthesis (DAA)] enhanced the fruitweight, but was ineffective when applied at 40 DAA. p-CPA– promoting of fruit growth increased as the applied concentration rose,so the weight of fruit treated by p-CPA at 500 mgL^–1 (the highest level) was the greatest in all plots;however the peel was considerably softer and abnormal swelling occurred in thenet. p-CPA applied to parthenocarpic fruit from 5 to 25DAAincreased sucrose content, the most effective application time being justbeforethe onset of sucrose accumulation (25 DAA). Fructose and glucose contents wereconsiderably lower than that of sucrose, and were not affected byp-CPA. p-CPA promoted sucroseaccumulation when applied to pollinated fruit, which showed the highest levelofenhancement in all plots. During the maturation period, the peel ofparthenocarpic fruit was a darker green color and the netting did not fullydevelop compared to pollinated fruit. p-CPA applicationsat10 or 25 DAA improved the peel color and netting of parthenocarpic fruits;therefore, the L value was similar to that of seeded fruit and the hue angledeclined. Applications of p-CPA during the early growthstage reduced the firmness of the mesocarp concomitant with increases in theapplied concentrations. p-CPA was present in the fruit atharvest, when applied from 10 to 25 DAA, even at 20 mgL^–1. The residue level increased as the appliedconcentration rose, but p-CPA was not detected in thenon-treated plot.     

Pharmacokinetics and safety of epinephrine use in liposuction

Patients are routinely exposed to high-dose epinephrine infiltration during large-volume liposuction. Because of the serious cardiovascular side-effect profile of catecholamine overdose, the authors examined the safety of larger-volume liposuction by assessing epinephrine pharmacokinetics. Five female volunteers with American Society of Anesthesiologists physical status of I or II, aged 29 to 40 years and weighing 75.9 to 95 kg, underwent liposuction. The wetting solution contained 7.3 mg (SEM, 0.7 mg) of epinephrine, corresponding to 0.09 mg/kg (0.04 mg/kg). Total plasma epinephrine and norepinephrine concentrations were assessed by high-performance liquid chromatography. Approximate exogenous epinephrine absorption was calculated after correction for estimated endogenous epinephrine production. Pharmacokinetic assessments were performed using standard equations. The total plasma epinephrine peak occurred at the final intraoperative reading (5 hours after induction) and was 323 pg/ml (24.8 pg/ml), three to four times maximum baseline resting levels. The norepinephrine level was slightly elevated throughout the study period, with a reversal of the normal epinephrine/norepinephrine ratio (<0.5:1) demonstrated intraoperatively (>5:1). Estimated time to peak exogenous epinephrine level ranged from 1 to 4 hours from the start of infiltration. Area under the plasma concentration versus time curve was approximately 2089 to 2610 pg x hour/ml. Peak exogenous epinephrine concentration was estimated to be 286 to 335 pg/ml. Clearance was 764,508 ml/hour and volume of distribution was 0.4 liter/kg (0.006 liter/kg). Total absorbed epinephrine was estimated, 1.8 mg to 2.2 mg, equivalent to 25 to 32 percent of the infiltrated dose. The reversal of the normal epinephrine/norepinephrine ratio and the fact that norepinephrine levels were within normal range implied that the majority of plasma epinephrine measured was exogenously infiltrated and not endogenously synthesized. On the basis of these observations, pharmacokinetic analyses were performed. Although unequivocal toxic epinephrine levels were not demonstrated, epinephrine peaks were three to four times the maximum observed in normal resting patients. Peak levels were comparable to those observed during major physiologic stresses, such as exercising to exhaustion, open abdominal surgery, or cross-clamping the aorta during surgical repair. Furthermore, epinephrine has been associated with myocardial infarction, arrhythmias, and fatal asystole in susceptible patients at these levels. Patients should be carefully screened for clinical evidence of hemodynamic and cardiac pathology before larger-volume liposuction is undertaken, as it may result in unnecessary high risk for patients who have preexisting cardiovascular disorders. Healthy American Society of Anesthesiologists physical status I or II patients should have sufficient cardiac reserve to tolerate these catecholamine levels.     

油菜品质育种现状及展望

国际油菜品质改良始于20世纪60年代,以降低油菜籽中芥酸和硫代葡萄糖苷为主要目标.随着历史的不断发展,油菜的品质改良已不再局限于这两个指标.在食用油方面,已将提高油酸、亚油酸含量,降低饱和脂肪酸和亚麻酸含量作为今后的主攻方向,使之成为最健康的食用油;在工业用油方面,高芥酸和中等长度的脂肪酸改良已逐渐展开.今后常规育种、杂种优势利用和生物技术的有机结合,将使油菜品种的改良进入到一个新的阶段.     

A 3-year experience of quality control and quality assurance in the multisite delivery of a lymphocyte-based cellular therapy for renal cell carcinoma

Autolymphocyte therapy (ALT) is outpatient-based adoptive immunotherapy using ex vivo-activated memory T-cells. To support the safe and reproducible delivery of ALT at three cell processing facilities (Boston, MA; Atlanta, GA; Orange, CA) we created a comprehensive quality assurance/quality control program compliant with recent FDA guidance relevant to activated lymphocytes and somatic cell therapies. Each facility performed extensive QC testing to ensure sterility, viability, and proper cell yield. Additonally, several QC tests were performed at Cellocr's centralized reference laboratory to monitor cell potency and identity of the ex vivo-processed lymphocytes. We report here the successful implementation of this QA/QC program for ALT which has resulted in the safe preparation and delivery of cell infusion products amounting to over 3600 treatments at seven clinical sites nationwide. We believe this program will serve as a model for other cellular therapies.     

大气质量提高与农业中的硫肥需求

论述了植物对硫素的生理需求,大气中含硫化合物的来源、组成与含量以及对植物生态系统的硫素补充作用,植物对气态硫化物的吸收、同化能力及适宜浓度等．近年来由于人类健康与生态环境的需要,世界各国纷纷通过法律体制对工业含硫废气的排放标准进行了严格控制,却导致了作物缺硫现象的频繁发生,在某些地区硫已成为限制农业生产的最重要肥料限制因素．为此,全球农业中硫肥的需求量猛增且有效性范围不断扩大,进而对硫肥的研究与开发利用提出了新的要求     

Microbiological quality and safety of zoo food

Two types of commercial products for feeding zoo animals (a frozen meat product, referred to as zoo food, and a dry product, referred to as dry food) were microbiologically examined for spoilage organisms (aerobic, psychrotrophic, coliform, Escherichia coli, mold, and yeasts) and pathogens (Salmonella spp., Listeria monocytogenes, and Campylobacter jejuni). Levels of microorganisms in frozen ground zoo food were compared with those in frozen ground beef and frozen ground turkey meat. The level of microbial contaminants in frozen ground zoo meat was found to be similar to that in frozen ground beef and higher than that in frozen ground turkey meat. Sixty percent of the frozen zoo meat samples were Salmonella positive, and all of the samples were L. monocytogenes positive. Dry zoo food was documented to have microbial levels lower than those in frozen zoo meat; the pathogen levels were less than 1/25 g of food. Defrosting zoo meat at 10, 25, and 37 degrees C for 24 h showed that 10 degrees C is the best temperature for defrosting frozen ground zoo meat loaves (length, 9 in. [22.8 cm]; radius, 2 in. [5.1 cm]) without affecting the microbiological quality or safety of the product.     

State legislative efforts to regulate use and potential misuse of genetic information.

The purpose of this study was to review existing and proposed legislation specifically intended to regulate the collection, use, and potential misuse of genetic data. The study encompasses laws relating to confidentiality, informed consent, discrimination, and related issues. It excludes from consideration legislation relating to medical records generally that may bear indirectly on genetic information. It also excludes both legislation relating to the regulation of DNA data collection for law enforcement purposes and state laws relating to the confidentiality of data collected by newborn-screening programs. While relatively few laws that explicitly regulate the treatment of genetic information have been enacted to date, a considerable amount of activity is currently underway in the nation's legislatures. Although most of the bills under consideration are not comprehensive in scope, they reflect a growing societal awareness that the uncontrolled dissemination and use of genetic data entails significant risks.     

Group living enhances individual resources discrimination: the use of public information by cockroaches to assess shelter quality

In group-living organisms, consensual decision of site selection results from the interplay between individual responses to site characteristics and to group-members. Individuals independently gather personal information by exploring their environment. Through social interaction, the presence of others provides public information that could be used by individuals and modulates the individual probability of joining/leaving a site. The way that individual's information processing and the network of interactions influence the dynamics of public information (depending on population size) that in turn affect discrimination in site quality is a central question. Using binary choice between sheltering sites of different quality, we demonstrate that cockroaches in group dramatically outperform the problem-solving ability of single individual. Such use of public information allows animals to discriminate between alternatives whereas isolated individuals are ineffective (i.e. the personal discrimination efficiency is weak). Our theoretical results, obtained from a mathematical model based on behavioral rules derived from experiments, highlight that the collective discrimination emerges from competing amplification processes relying on the modulation of the individual sheltering time without shelters comparison and communication modulation. Finally, we well demonstrated here the adaptive value of such decision algorithm. Without any behavioral change, the system is able to shift to a more effective strategy when alternatives are present: the modification of the spatio-temporal distributions of individuals leading to the collective selection of the best resource. This collective discrimination implying such parsimonious and widespread mechanism must be shared by many group living-species.     

Unisite and multisite catalysis in the ArsA ATPase

The ars operon of plasmid R773 encodes an As(III)/Sb(III) extrusion pump. The catalytic subunit, the ArsA ATPase, has two homologous halves, A1 and A2, each with a consensus nucleotide-binding sequence. ATP hydrolysis is slow in the absence of metalloid and is accelerated by metalloid binding. ArsA M446W has a single tryptophan adjacent to the A2 nucleotide-binding site. Tryptophan fluorescence increased upon addition of ATP, ADP, or a nonhydrolyzable ATP analogue. Mg(2+) and Sb(III) produced rapid quenching of fluorescence with ADP, no quenching with a nonhydrolyzable analogue, and slow quenching with ATP. The results suggest that slow quenching with ATP reflects hydrolysis of ATP to ADP in the A2 nucleotide-binding site. In an A2 nucleotide-binding site mutant, nucleotides had no effect. In contrast, in an A1 nucleotide-binding mutant, nucleotides still increased fluorescence, but there was no quenching with Mg(2+) and Sb(III). This suggests that the A2 site hydrolyzes ATP only when Sb(III) or As(III) is present and when the A1 nucleotide-binding domain is functional. These results support previous hypotheses in which only the A1 nucleotide-binding domain hydrolyzes ATP in the absence of activator (unisite catalysis), and both the A1 and A2 sites hydrolyze ATP when activated (multisite catalysis).     

Nicotinamide enhances mitochondria quality through autophagy activation in human cells

Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential (ΔΨ m ) by accelerating autophagic degradation of mitochondria. In the NAM-treated cells, the level of LC3-II as well as the number of LC3 puncta and lysosomes co-localizing with mitochondria substantially increased. Furthermore, in the NAM-treated cells, the levels of Fis1, Drp1, and Mfn1, proteins that regulate mitochondrial fission and fusion, increased and mitochondria experienced dramatic changes in structure from filaments to dots or rings. This structural change is required for the decrease of mitochondrial mass indicating that NAM accelerates mitochondrial autophagy, at least in part, by inducing mitochondrial fragmentation. The decrease in mitochondria mass was attenuated by treatment with cyclosporine A, which prevents the loss of mitochondrial membrane potential by blocking the mitochondrial permeability transition, suggesting autophagic degradation selective for mitochondria with low ΔΨ m . All these changes were accompanied by and dependent on an increase in the levels of GAPDH, and are blocked by inhibition of the cellular conversion of NAM to NAD⁺. Taken together with our previous findings, these results suggest that up-regulation of GAPDH activity may prolong healthy lifespan of human cells through autophagy-mediated mitochondria quality maintenance.     

Daidzein enhances intramuscular fat deposition and improves meat quality in finishing steers

An experiment was conducted to determine the effects of soy isoflavone daidzein on carcass characteristics, fat deposition, meat quality, and blood metabolites in finishing steers. Fourteen crossbred steers were used in a 120-d finishing study. These steers were stratified by weight into groups and randomly allotted by group to one of two dietary treatments: (1) control and (2) daidzein (500 mg/kg concentrate). The steers were fed a 90% concentrate diet. Supplemental daidzein did not affect slaughter weight, hot carcass weight, and dressing percentage, but tended to reduce fat proportion (not including intramuscular fat) in carcass and backfat thickness of steers. The carcass bone proportion was greater in steers fed daidzein diets than those fed control diets. Daidzein supplementation reduced pH at 24 h after slaughtered and moisture content and increased isocitrate dehydrogenase activity, fat content (16.28% and 7.94%), marbling score (5.29 and 3.36), redness (a*), and chroma (C*) values in longissimus muscle relative to control treatment. The concentrations of blood metabolites including glucose, blood urea nitrogen, triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were all lower in steers fed daidzein diets than those fed control diets. Current results suggest that supplemental daidzein can affect lipid metabolism, increase intramuscular fat content and marbling score, and improve meat quality in finishing steers. Daidzein should be a promising feed additive for production of high-quality beef meat.     

Lactic acid bacteria in the quality improvement and depreciation of wine

The winemaking process includes two main steps: lactic acid bacteria are responsible for the malolactic fermentation which follows the alcoholic fermentation by yeasts. Both types of microorganisms are present on grapes and on cellar equipment. Yeasts are better adapted to growth in grape must than lactic acid bacteria, so the alcoholic fermentation starts quickly. In must, up to ten lactic acid bacteria species can be identified. They belong to the Lactobacillus, Pediococcus, Leuconostoc and Oenococcus genera. Throughout alcoholic fermentation, a natural selection occurs and finally the dominant species is O. oeni, due to interactions between yeasts and bacteria and between bacteria themselves. After bacterial growth, when the population is over 10⁶CFU/ml, malolactic transformation is the obvious change in wine composition. However, many other substrates can be metabolized. Some like remaining sugars and citric acid are always assimilated by lactic acid bacteri a, thus providing them with energy and carbon. Other substrates such as some amino acids may be used following pathways restricted to strains carrying the adequate enzymes. Some strains can also produce exopolysaccharides. All these transformations greatly influence the sensory and hygienic quality of wine. Malic acid transformation is encouraged because it induces deacidification. Diacetyl produced from citric acid is also helpful to some extent. Sensory analyses show that many other reactions change the aromas and make malolactic fermentation beneficial, but they are as yet unknown. On the contrary, an excess of acetic acid, the synthesis of glucane, biogenic amines and precursors of ethylcarbamate are undesirable. Fortunately, lactic acid bacteria normally multiply in dry wines; moreover some of these activities are not widespread. Moreover, the most striking trait of wine lactic acid bacteria is their capacity to adapt to a hostile environment. The mechanisms for this are not yet c ompletely elucidated . Molecular biology has provided some explanations for the behaviour and the metabolism of bacteria in wine. New tools are now available to detect the presence of desirable and undesirable strains. Even if much remains unknown, winemakers and oenologists can nowadays better control the process. By acting upon the diverse microflora and grape musts, they are more able to produce healthy and pleasant wines.     

微生物改善烟叶品质研究进展

从微生物缩短烟叶发酵时间、降低烟叶有害成分、增加烟叶香气等方面概述了微生物在改善烟叶品质方面的研究进展,并对其在烟叶上的应用前景作了分析。