Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP), thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta deposits at the same age; however, relative to JNPL3 mice, the double mutants exhibited neurofibrillary tangle pathology that was substantially enhanced in the limbic system and olfactory cortex. These results indicate that either APP or Abeta influences the formation of neurofibrillary tangles. The interaction between Abeta and tau pathologies in these mice supports the hypothesis that a similar interaction occurs in Alzheimer's disease.     

The analgesic and sedative effects of GV20 pharmacopuncture with low-dose hydromorphone in healthy dogs undergoing ovariohysterectomy

This study evaluates the analgesic efficacy of low-dose hydromorphone administered via pharmacopuncture at Governing Vessel 20 (GV20) for postoperative pain management following canine ovariohysterectomy. Fifty clinically healthy female dogs undergoing ovariohysterectomy were allocated to receive hydromorphone [0.1 mg/kg body weight (BW)] intramuscularly (IM, n = 25) or hydromorphone (0.01 mg/kg BW) pharmacopuncture at GV20 (GV, n = 25) following extubation. This was a prospective, blinded, randomized clinical trial. Pain and sedation scores were evaluated using the Glasgow Composite Measure Pain Scale Short Form (CMPS-SF) at 1, 2, 3, 4, and 12 hours following study treatment. Time of treatment failure (CMPS-SF ≥ 6/24) was recorded and analyzed using Kaplan-Meier survival analysis. Patient demographics and duration of surgery and anesthesia were analyzed using the appropriate unpaired Student’s t-test. The Glasgow CMPS-SF and sedation score were analyzed using a repeated measures 2-way analysis of variance (ANOVA) followed by Bonferroni post-test where appropriate. Significance was set a P < 0.05. There were no significant differences in patient demographics, anesthesia and surgery duration, and study treatment failure. The Glasgow CMPS-SF scores were significantly higher for IM compared with GV [2 (0 to 8) versus 1 (0 to 6), respectively; P = 0.044] at 4 hours. Sedation scores were significantly higher for IM compared with GV at 2 [2 (1 to 3) and 1 (1 to 3), respectively; P = 0.0004] and 4 [1 (1 to 3) and 1 (1 to 2), respectively; P = 0.03] hours. Pharmacopuncture with low-dose hydromorphone provided adequate postoperative analgesia in dogs undergoing ovariohysterectomy with reduced sedative effects. Pharmacopuncture is a good alternative in dogs when reduced dosing of opioids is recommended.     

Linkage of plasma Abeta42 to a quantitative locus on chromosome 10 in late-onset Alzheimer's disease pedigrees

Plasma Abeta42 (amyloid beta42 peptide) is invariably elevated in early-onset familial Alzheimer's disease (AD), and it is also increased in the first-degree relatives of patients with typical late-onset AD (LOAD). To detect LOAD loci that increase Abeta42, we used plasma Abeta42 as a surrogate trait and performed linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma Abeta. Here, we report linkage to chromosome 10 with a maximal lod score of 3.93 at 81 centimorgans close to D10S1225. Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase Abeta.     

肉鸡生产管理

鸡的需要 　　肉鸡的生物需要与其它畜禽相似：环境保护、饲料和水。另外，养殖肉鸡必须把饲料尽可能有效地转化成动物蛋白。当肉鸡的需要得到满足后，肉鸡生产效率就达到最佳。然而，典型的生产企业是否能持续稳定地保证肉鸡最佳生产的需要 ?答案是否定的。 　　实际生产中很少能完全达到肉鸡的遗传潜力。因此问题就变成，实际生产条件下能够实现多少 ?一般来讲，最好的养殖企业能达到的水平应是所有养殖者都能达到的，虽然它们的肉鸡生产性能仍显著地低于肉鸡的遗传潜力。今天美国肉鸡场一般都可提供环境保护、饲料和水，但为什么同样品系…     

Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria

Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.     

Planetary Contamination II: Soviet and U.S. Practices and Policies

The accompanying article of Horo witz et al. concluded with the view that the COSPAR recommendations re garding Mars should be adjusted to re flect new environmental information. Specifically, it was concluded that viable terrestrial microorganisms which are transported to Mars inside solid components in sealed spaces have a low probability of being released to the sur face or atmosphere, and that, if any are released, they are not likely to in fect the planet. We suggest, in addition, that both the COSPAR recommenda tions and U.S. planetary quarantine policy should be altered to take into account past and continuing Soviet prac tice regarding the. exploration of Mars and Venus. No amount of analysis by COSPAR, or of costly, self-imposed restrictions by the U.S. on its own planetary exploration program, can reduce the probability of contamination of either Venus or Mars below what the Soviets have already made it, or will make it as they continue their large planetary effort. All that U.S. policy can accomplish is to insure that U.S. efforts do not significantly increase the probability above that level. Any rec ommended policy which would require the U.S. to apply significantly more stringent restrictions is illogical in that, in effect, the U.S. would be asked to increase greatly the cost and complexity of its planetary program without achieving any significant reduction in the probability of actual contamination. There exists some parallelism be tween the problem of planetary quaran tine and that of radioactive fallout from atmospheric nuclear testing, al though the desirable solution to the quarantine problem is not merely to stop all activity. Both are multilateral problems, and individual national policy necessarily must reflect the policy of other nations. Thus, the real questions that must be faced by COSPAR, and by the U.S., are, (i) What is the prob able number of viable terrestrial micro organisms alreadyr transported to Venus and to Mars? and (ii) What is the to tal number to be expected in the next decade or so from foreseeable Soviet efforts alone? Then COSPAR can rec ommend, and the U.S. can decide, that the total U.S. contribution should be equal to some specified fraction of the total present and future Soviet contribu tion. This approach in turn suggests that every effort should be made to induce the Soviets to supply additional de tails on the Zond 2 and Venus 3 mis sion and trajectory and, particularly, on the procedure used for sterilizing the components and assembly of both space craft. With such information, the proba ble number of viable terrestrial microor ganisms deposited on Venus and Mars could be estimated well enough to per mit a. realistic quantitative analysis of what U.S. policy and practice should be. However, if more complete informa tion on Soviet practice cannot be ob tained, then, it seems to us, the U.S. has no logical alternative but to per mit greater engineering freedom in lander delivery technique and to ac cept gaseous and other nonthermal sterilization procedures, where neces sary, in its own program. By relying on the demonstrated U.S. spacecraft reliability to insure that the U.S. con tribution to planetary contamination will remain significantly less than the Soviet contribution, we could reduce significantly the cost and time required to carry out serious scientific investiga tions of the surfaces of Venus and Mars.