BACKGROUND & AIMS: :Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.

背景与目标： : 各种因素，包括实验动物与人类之间的系统发育距离，当前的体外系统与人体之间的差异以及计算机模拟的限制，都需要新的解决方案来解决全球范围内不断增长的难题。物质测试。这篇评论提供了关于这一困境加剧的历史草图，并强调了迄今为止采取的对策的根本局限性。它描述了最近引入的微系统在 “芯片上的器官” 设备中模拟人体器官的潜力。最后，它着重于对旨在模仿 “芯片上的人” 系统中人体全身器官相互作用的第一批设备的深入分析。讨论了它们替代动物急性全身毒性测试的潜力，以及它们无法提供重复剂量长期测试的替代方法。受人类生物学，组织工程和微系统技术的最新发现的启发，这篇评论提出了一种范式转变，以克服明显的挑战。概述了在 “芯片上的人” 系统中创建新的生物稳态水平的路线图，以便从长远来看取代动物的系统重复剂量安全性评估和疾病建模。

BACKGROUND & AIMS: :Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. The present study aims to investigate whether the ribozyme could reverse MDR in breast carcinoma cells. In this study, two GUC sites (GUC106 and GUC135) on the surface of mdr1 mRNA were selected according to the secondary structure of the 5'-region of mdrl mRNA. The ribozyme gene RZ106 and RZ135 complementary to two sides bases of the target GUC were synthesized and cloned into the plasmid pEGFP -C1 which has EGFP (Enhanced Green Fluorescence Protein) as report gene and Kan/Neo as selection gene. After transfection with the recombinant plasmid and selected by G418, the stable cell clones were produced and used for detection. The alteration of mdr1 mRNA and P-gp in the treated cells was detected by RT-PCR, flow cytometry and Rh123 retention. The reversal efficiency of the drug resistance for adriamycin was determined by MTT assay. The results showed that after transfection with RZ106 and RZ135, the amount of the mdr1 mRNA and P-gp decreased significantly and the efflux function of P-gp was inhibited accordingly. Nine-fold and 16-fold reduction of resistance for adriamycin was observed in the two groups of treated cells. These results suggested that both ribozymes can reverse the MDR phenotype by inhibiting the expression of mdr1 mRNA and P-gp, and the RZ135 showed the better cleavage efficiency. The ribozyme strategy designed according the secondary structure of the target RNA could be a useful therapy for reversal of MDR.

背景与目标： 多药耐药 (MDR) 是癌症化疗的主要障碍。本研究旨在研究核酶是否可以逆转乳腺癌细胞中的MDR。在这项研究中，根据mdrl mRNA的5 '-区的二级结构选择了mdr1 mRNA表面的两个GUC位点 (GUC106和GUC135)。合成了与目标GUC的两个碱基互补的核酶基因RZ106和RZ135，并将其克隆到质粒pEGFP -C1中，该质粒以EGFP (增强绿色荧光蛋白) 为报告基因，以Kan/Neo为选择基因。用重组质粒转染并经G418筛选后，产生稳定的细胞克隆并用于检测。通过rt-pcr，流式细胞术和Rh123保留检测处理的细胞中mdr1 mRNA和P-gp的变化。通过MTT法确定阿霉素耐药性的逆转效率。结果表明，转染RZ106和RZ135后，mdr1 mRNA和P-gp的量显着降低，P-gp的外排功能受到相应的抑制。在两组处理过的细胞中，阿霉素的耐药性降低了9倍和16倍。这些结果表明，两种核酶都可以通过抑制mdr1 mRNA和P-gp的表达来逆转MDR表型，并且RZ135显示出更好的切割效率。根据靶RNA的二级结构设计的核酶策略可能是逆转MDR的有用疗法。

BACKGROUND & AIMS: OBJECTIVE:To determine the efficiency of oocyte cryopreservation relative to IVF with unfrozen oocytes. DESIGN:Meta-analysis. SETTING:Academic assisted reproduction center. PATIENT(S):Results of all reports from January 1997 to June 2005 with the patients undergoing IVF-intracytoplasmic sperm injection (ICSI) with cryopreserved cycles between 1996 and 2004 were compared with those of patients who underwent IVF-ICSI with unfrozen oocytes in 2002 and 2003 in our program. INTERVENTION(S):Mean age and number of ET cycles originating from unfrozen oocytes was matched with those for thaw cycles originating from oocytes cryopreserved with a slow-freezing (SF) protocol. Vitrification (VF) reports were not included in the comparative analysis because of a small number of pregnancies (10) before June 2005. MAIN OUTCOME MEASURE(S):The comparison of fertilization rate, clinical pregnancy, and live-birth rates per injected oocyte, clinical pregnancy and live-birth rates per transfer, and implantation rate between IVF-ICSI cycles with frozen and unfrozen oocytes. RESULT(S):Live-birth rates per oocyte thawed were 1.9% and 2.0% for SF and VF, respectively, before June 2005. Live-birth rates per injected oocyte and ET, respectively, were 3.4% and 21.6% for SF and were 6.6% and 60.4% for IVF with unfrozen oocytes. Compared to women who underwent IVF after SF, IVF with unfrozen oocytes resulted in significantly better rates of fertilization (odds ratio [95% confidence interval]); 2.22 (1.80, 2.74), of live birth per injected oocyte; 1.5 (1.26, 1.79), and of implantation; 4.66 (3.93, 5.52). These odds ratios were lower when oocyte cryopreservation success rates from 2002-2004 were compared with those for IVF with unfrozen oocytes. When the reports after June 2005 were considered, this trend did not appear to continue. With the consideration of VF reports after June 2005, however, higher pregnancy rates were achieved. CONCLUSION(S):In vitro fertilization success rates with slow-frozen oocytes are significantly lower when compared with the case of IVF with unfrozen oocytes. Although oocyte cryopreservation with the SF method appears to be justified for preserving fertility when a medical indication exists, its value for elective applications remains to be determined. Pregnancy rates with VF appear to have improved, but further studies will be needed to determine the efficiency and safety of this technique.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Neuro-ventilatory efficiency (NVE), defined as the tidal volume to electrical diaphragm-activity ratio (VT/EAdi) at the beginning and end of the weaning process after acute hypoxaemic respiratory failure, may provide valuable information about patient recovery. METHODS:This observational study included 12 patients breathing with neurally adjusted ventilatory assist (NAVA). When a spontaneous breathing trial (SBT) with pressure support of 7 cm H2O and PEEP was unsuccessful, NAVA was used and the level was adjusted to obtain an EAdi of ∼60% of maximal EAdi during SBT. VT and EAdi were recorded continuously. We compared changes in NVE between NAVA and SBT at the first failed and first successful SBT. RESULTS:When patients were switched from NAVA to SBT, NVE was significantly reduced during both unsuccessful and successful SBT (-56 and -38%, respectively); however, this reduction was significantly lower when SBT was successful (P=0.01). Between the first and last day of weaning, we observed that NVE decreased with NAVA [40.6 (27.7-89.5) vs 28.8 (18.6-46.7); P=0.002] with a significant decrease in NAVA level, whereas it remained unchanged during SBT [15.4 (10.7-39.1) vs 19.5 (11.6-29.6); P=0.50] with significant increases in both EAdi and VT and no difference in respiratory rhythm. CONCLUSIONS:These results suggest that in patients after respiratory failure and prolonged mechanical ventilation, changes in VT and NVE, between SBTs are indicative of patient recovery. Larger clinical trials are needed to clarify whether changes in NVE reliably predict weaning in patients ventilated with NAVA.

背景与目标：

BACKGROUND & AIMS: :The effects of pre-treatment methods on saccharification and hydrogen fermentation of Chlorella pyrenoidosa biomass were investigated. When raw biomass and biomass pre-treated by steam heating, by microwave heating, and by ultrasonication were used as feedstock, the hydrogen yields were only 8.8-12.7 ml/g total volatile solids (TVS) during dark fermentation. When biomass was pre-treated by steam heating with diluted acid and by microwave heating with diluted acid, the dark hydrogen yields significantly increased to 75.6 ml/g TVS and 83.3 ml/g TVS, respectively. Steam heating with diluted acid is the preferred pre-treatment method of C. pyrenoidosa biomass to improve hydrogen yield during dark fermentation and photofermentation, which is followed by methanogenesis to increase energy conversion efficiency (ECE). A total hydrogen yield of 198.3 ml/g TVS and a methane yield of 186.2 ml/g TVS corresponding to an overall ECE of 34.0% were obtained through the three-stage process (dark fermentation, photofermentation, and methanogenesis).

背景与目标： : 研究了预处理方法对小球藻生物质糖化和氢发酵的影响。当使用通过蒸汽加热，通过微波加热和通过超声处理的原始生物质和生物质作为原料时，在黑暗发酵期间，氢产率仅为8.8-12.7毫升/g总挥发性固体 (TVS)。当通过用稀酸进行蒸汽加热和用稀酸进行微波加热对生物质进行预处理时，暗氢产量分别显著增加至75.6毫升/g TVS和83.3毫升/g TVS。用稀酸蒸汽加热是C. pyrenoidosa生物质的首选预处理方法，以提高黑暗发酵和光发酵过程中的氢产量，随后是甲烷生成以提高能量转化效率 (ECE)。通过三阶段过程 (暗发酵、光发酵和产甲烷) 获得了198.3毫升/g TVS的总氢产率和186.2毫升/g TVS的甲烷产率，对应于34.0% 的总ECE。

BACKGROUND & AIMS: BACKGROUND:Cognitive Behaviour Therapy (CBT) is the front-line psychological intervention for step 3 within UK psychological therapy services. Counselling is recommended only when other interventions have failed and its effectiveness has been questioned. METHOD:A secondary data analysis was conducted of data collected from 33,243 patients across 103 Improving Access to Psychological Therapies (IAPT) services as part of the second round of the National Audit of Psychological Therapies (NAPT). Initial analysis considered levels of pre-post therapy effect sizes (ESs) and reliable improvement (RI) and reliable and clinically significant improvement (RCSI). Multilevel modelling was used to model predictors of outcome, namely patient pre-post change on PHQ-9 scores at last therapy session. RESULTS:Counselling received more referrals from patients experiencing moderate to severe depression than CBT. For patients scoring above the clinical cut-off on the PHQ-9 at intake, the pre-post ES (95% CI) for CBT was 1.59 (1.58, 1.62) with 46.6% making RCSI criteria and for counselling the pre-post ES was 1.55 (1.52, 1.59) with 44.3% of patients meeting RCSI criteria. Multilevel modelling revealed a significant site effect of 1.8%, while therapy type was not a predictor of outcome. A significant interaction was found between the number of sessions attended and therapy type, with patients attending fewer sessions on average for counselling [M = 7.5 (5.54) sessions and a median (IQR) of 6 (3-10)] than CBT [M = 8.9 (6.34) sessions and a median (IQR) of 7 (4-12)]. Only where patients had 18 or 20 sessions was CBT significantly more effective than counselling, with recovery rates (95% CIs) of 62.2% (57.1, 66.9) and 62.4% (56.5, 68.0) respectively, compared with 44.4% (32.7, 56.6) and 42.6% (30.0, 55.9) for counselling. Counselling was significantly more effective at two sessions with a recovery rate of 34.9% (31.9, 37.9) compared with 22.2% (20.5, 24.0) for CBT. CONCLUSIONS:Outcomes for counselling and CBT in the treatment of depression were comparable. Research efforts should focus on factors other than therapy type that may influence outcomes, namely the inherent variability between services, and adopt multilevel modelling as the given analytic approach in order to capture the naturally nested nature of the implementation and delivery of psychological therapies. It is of concern that half of all patients, regardless of type of intervention, did not show reliable improvement.

背景与目标：

BACKGROUND & AIMS: CONTEXT:Hydrogels are promising polymeric network capable of sustaining the release of drug but have a major limitation for encapsulation of hydrophobic drugs. OBJECTIVE:This study was undertaken to encapsulate etoposide in poloxamer 407-based thermosensitive hydrogels with an aim to sustain its release. MATERIALS AND METHODS:Etoposide-loaded hydrogels were prepared by the cold method and optimized for encapsulation efficiency (EE) by a 3(2) factorial design. Poloxamer 407-poloxamer 188 hydrogel (E-P407-P188) and poloxamer 407-poly(ethylene glycol) (E-P407-PEG) hydrogel were characterized for SEM, swelling, sol-gel phase transition and injectability study. RESULTS AND DISCUSSION:In E-P407-P188 hydrogel the EE of 75% could be obtained and in E-P407-PEG hydrogels the EE was 84%. The SEM images showed a porous structure. The release of ETO was sustained up to 48 h by E-P407-PEG hydrogel and 24 h by E-P407-P188 hydrogel. The drug release was governed by first-order kinetics and followed Fickian diffusion mechanism in both the cases. CONCLUSION:Such injectable thermosensitive hydrogel of etoposide could be effectively used for continuous release of drug to the tumor and surrounding tissues.

背景与目标：

BACKGROUND & AIMS: CONTEXT:Diagnostic efficiency is important in daily clinical practice as doctors have to face problems within a limited time frame. To foster the clinical reasoning of students is a major challenge in medical education research. Little is known about students' diagnostic efficiency. On the basis of current theories, scaffolds for case representation (statement of the case as far as it is summarised in the mind) could be a promising approach to make the diagnostic reasoning of intermediate medical students more efficient. METHODS:Clinical case processing of 88 medical students in their fourth and fifth years was analysed in a randomised, controlled laboratory study. Cases dealing with dyspnoea were provided in an electronic learning environment (CASUS). Students could freely choose the time, amount and sequence of clinical information. During the learning phase the intervention group was asked to write down case representation summaries while working on the cases. In the assessment phase diagnostic efficiency was operationalised as the number of correct diagnoses divided by the time spent on diagnosing. RESULTS:Diagnostic efficiency was significantly improved by the representation scaffolding (M = 0.12 [SD = 0.07], M = 0.09 [SD = 0.06] correct cases/time, p = 0.045), whereas accuracy remained unchanged (M = 2.28 [SD = 1.10], M = 2.09 [SD = 1.08], p = 0.52). Both groups screened the same amount of clinical information, but the scaffolding group did this faster (M = 20.8 minutes [SD = 7.15], M = 24.6 minutes [SD = 7.42], p = 0.01; Cohen's d = 0.5). CONCLUSION:Diagnostic efficiency is an important outcome variable in clinical reasoning research as it corresponds to workplace challenges. Scaffolding for case representations significantly improved the diagnostic efficiency of fourth and fifth-year medical students, most likely because of a more targeted screening of the available information.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Gene therapy has been a hot spot in repair of bone defects in recent years. This study aimed to construct a recombinant plasmid pcDNA3.1-VEGF(165), and to observe the effect of vascular endothelial growth factor 165 (VEGF(165)) gene therapy on bone defects in rabbits. METHODS:Total RNA was extracted from rabbit bone tissues. VEGF(165) cDNA fragment was prepared by reverse transcription and the gene was cloned by polymerase chain reaction (PCR). Plasmid pMD18-T/VEGF(165) combined with pcDNA3.1 was cloned to reconstruct pcDNA3.1-VEGF(165) plasmid. Thirty New Zealand white rabbits weighing (2.50 +/- 0.13) kg were used to establish models of bone defects (1 cm in length) of the bilateral radii. The bone defects were repaired with absorbable gelatin sponge. After the operation, physiological sodium chloride solution was injected into the injured site in one of the forelegs of the rabbits as the control group, and pcDNA3.1-VEGF(165) plasmid (0.2 ml, 200 ng) was injected into the opposite foreleg as the experiment groups. At weeks 1, 2, 4, 6, 8, and 12 after the treatments, the bones were examined by X-ray, and the specimens of the bone defects were collected, stained with HE, and observed under a light microscope. The expression of VEGF(165) mRNA was examined by real-time quantitative polymerase chain reaction (RQ-PCR). RESULTS:The pcDNA3.1-VEGF(165) plasmid with a correct sequence was constructed successfully. Postoperative X-ray found no difference between the two groups at week 1. In the experiment group, callus and synostosis were observed after 2 weeks, and osteosis structure was normal at week 12; these phenomena occurred much later in the control group. In the experiment group, HE staining showed a large amount of newly formed blood vessels after 2 weeks, a number of bone trabeculae with osteoblasts proliferation at 4 weeks, and fresh bone cortex and reformed medullary cavity at 12 weeks; whereas in the control group these structures formed in later phases. The VEGF(165) mRNA in the experiment group was expressed at a low level at week 1, reached the peak at weeks 3, and then decreased to a normal level after 6 weeks. CONCLUSIONS:Local use of pcDNA3.1-VEGF(165) plasmid at bone defects can upregulate the expression of VEGF(165) and accelerate the formation of capillaries and the repair of bone defects. Angiogenesis and osteogenesis can be promoted by a combination of pcDNA3.1-VEGF(165) and gelatin sponge.

背景与目标：

BACKGROUND & AIMS: :Nitrification inhibitors (NIs) are used to retard the nitrification process and reduce nitrogen (N) losses. However, the effects of soil properties on NI efficacy are less clear. Moreover, the direct and indirect effects of soil property variations on NI efficiency in minimizing carbon dioxide (CO2) emissions have not been previously studied. An incubation experiment was conducted for 40 days with two treatments, N (200 mg N-urea kg-1) and N + dicyandiamide (DCD) (20 mg DCD kg-1), and a control group (without the N) to investigate the response of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to DCD application and the consequences for CO2, nitrous oxide (N2O) and ammonia (NH3) emissions from six soils from the Loess Plateau with different properties. The nitrification process completed within 6-18 days for the N treatment and within 30->40 days for the N + DCD treatment. AOB increased significantly with N fertilizer application, while this effect was inhibited in soils when DCD was applied. AOA was not sensitive to N fertilizer and DCD application. The nitrification rate was positively correlated with the clay (p < 0.05) and SOM contents (p < 0.01); DCD was more effective in loam soil with low SOM and high soil pH. Soil pH significantly was decreased with N fertilizer application, while it increased when DCD was applied. Moreover, DCD application decreased CO2 emissions from soils by 22%-172%; CO2 emissions were negatively correlated with the clay and SOM contents. DCD application decreased N2O emissions in each soil by 1.0- to 94-fold compared with those after N fertilizer application. In contrast, DCD application increased NH3 release from soils by 59-278%. NH3 volatilization was negatively correlated with clay (p < 0.05) and SOM (p < 0.01) contents and positively correlated with soil pH (p < 0.01). Therefore, soil texture, SOM and soil pH have significant effects on the DCD performance, nitrification process and gaseous emissions.

背景与目标： : 硝化抑制剂 (NIs) 用于延缓硝化过程并减少氮 (N) 损失。然而，土壤性质对镍功效的影响尚不清楚。此外，以前尚未研究土壤性质变化对NI效率的直接和间接影响，以最大程度地减少二氧化碳 (CO2) 排放。用N (200 mg N-ure 1千克-1) 和N + 双氰胺 (DCD) (20 mg DCD kg-1) 两种处理进行孵育实验40天，和对照组 (不含N) 研究氨氧化细菌 (AOB) 和古细菌 (AOA) 对DCD施用的响应以及六种土壤中CO2，一氧化二氮 (N2O) 和氨 (NH3) 排放的后果。黄土高原具有不同的性质。硝化过程在N处理的6-18天内完成，在N DCD处理的30->40天内完成。施用氮肥后，AOB显着增加，而施用DCD时，这种作用在土壤中受到抑制。AOA对氮肥和DCD施用不敏感。硝化率与粘土 (p < 0.05) 和SOM含量 (p < 0.01) 呈正相关。DCD在SOM低，土壤pH高的壤土中更有效。施用氮肥后，土壤ph值显着降低，而施用DCD时，土壤ph值升高。此外，施用DCD可使土壤中的CO2排放量降低22%-172%; CO2排放量与粘土和SOM含量呈负相关。与施用氮肥后相比，施用DCD可使每种土壤中的N2O排放量减少1.0至94倍。相反，施用DCD使土壤中的NH3释放增加了59-278%。NH3挥发与粘土 (p < 0.05) 和SOM (p < 0.01) 含量呈负相关，与土壤pH呈正相关 (p <0.01)。因此，土壤质地，SOM和土壤pH对DCD性能，硝化过程和气体排放有显着影响。

BACKGROUND & AIMS: :Developmental abnormalities associated with the cloning process suggest that reprogramming of donor nuclei into an embryonic state may not be fully completed in most of the cloned animals. One of the areas of interest in this regard, is the analysis of gene expression patterns in nuclear transfer (NT) embryos to dissect the processes that failed and develop means to overcome the limitations imposed by these factors. In this study, we investigated expression patterns of histone deacetylase-1, -2, -3 (HDAC-1, -2, -3), DNA methyltransferase-3a (DNMT3A), and octamer binding protein-4 gene (OCT4) in donor cells with different cloning efficiencies and NT embryos derived from these cells employing a real-time RT-PCR assay. All genes investigated followed altered expression patterns in NT embryos when compared to IVF-derived embryos. In general, expression of HDAC genes was elevated especially at the compact morula stage and comparable to in vitro fertilized (IVF) embryos at the hatched blastocyst stage. DNMT3A expression in NT embryos was lower than IVF embryos at all stages. Oct-4 transcript levels were also reduced in cloned compared to IVF embryos at the compact morula and blastocyst stages. This difference disappeared at the hatched blastocyst stage. There was a donor cell effect on the expression patterns of all genes investigated. These results demonstrate altered gene expression patterns for certain genes, in cloned cattle embryos from our donor cells of different efficiency in producing live offspring. Therefore we suggest that differences in expression of developmentally important genes during early embryo development may characterize the efficiency of donor cells in producing live offspring.

背景与目标： : 与克隆过程相关的发育异常表明，在大多数克隆动物中，供体核重编程为胚胎状态可能尚未完全完成。在这方面，感兴趣的领域之一是分析核转移 (NT) 胚胎中的基因表达模式，以剖析失败的过程，并开发克服这些因素所施加限制的手段。在这项研究中，我们研究了组蛋白deacetylase-1，-2，-3 (HDAC-1，-2，-3)，DNA methyltransferase-3a (DNMT3A)，和八聚体结合蛋白4基因 (OCT4) 在具有不同克隆效率的供体细胞中，以及使用实时rt-pcr分析从这些细胞衍生的NT胚胎。与IVF衍生的胚胎相比，所研究的所有基因均遵循NT胚胎中表达模式的改变。通常，HDAC基因的表达升高，尤其是在紧凑的桑ula阶段，与孵化的胚泡阶段的体外受精 (IVF) 胚胎相当。在所有阶段，NT胚胎中DNMT3A的表达均低于IVF胚胎。与紧凑型桑ula和胚泡期的IVF胚胎相比，克隆的10月-4转录本水平也降低。这种差异在孵化的胚泡阶段消失了。对所有研究基因的表达模式都有供体细胞影响。这些结果表明，在来自我们的供体细胞的克隆牛胚胎中，某些基因的基因表达模式发生了改变，这些基因在生产后代方面效率不同。因此，我们建议在早期胚胎发育过程中发育重要基因表达的差异可能是供体细胞产生活后代的效率的特征。

BACKGROUND & AIMS: :We showed recently that exposure to whisker vibrations enhances coding efficiency in rat barrel cortex despite increasing correlations in variability (Adibi et al., 2013). Here, to understand how adaptation achieves this improvement in sensory representation, we decomposed the stimulus information carried in neuronal population activity into its fundamental components in the framework of information theory. In the context of sensory coding, these components are the entropy of the responses across the entire stimulus set (response entropy) and the entropy of the responses conditional on the stimulus (conditional response entropy). We found that adaptation decreased response entropy and conditional response entropy at both the level of single neurons and the pooled activity of neuronal populations. However, the net effect of adaptation was to increase the mutual information because the drop in the conditional entropy outweighed the drop in the response entropy. The information transmitted by a single spike also increased under adaptation. As population size increased, the information content of individual spikes declined but the relative improvement attributable to adaptation was maintained.

背景与目标： : 我们最近表明，尽管变异性之间的相关性增加，但暴露于晶须振动仍可提高大鼠桶皮层中的编码效率 (Adibi等，2013)。在这里，为了了解适应如何实现感官表现的这种改善，我们在信息论的框架内将神经元群体活动中携带的刺激信息分解为其基本组成部分。在感官编码的上下文中，这些成分是整个刺激集的响应的熵 (响应熵) 和以刺激为条件的响应的熵 (条件响应熵)。我们发现，适应在单个神经元水平和神经元群体的合并活动上都降低了响应熵和条件响应熵。但是，适应的净效果是增加互信息，因为条件熵的下降超过了响应熵的下降。在适应的情况下，单个峰值传输的信息也会增加。随着人口规模的增加，单个峰值的信息含量下降，但归因于适应的相对改善得以保持。

BACKGROUND & AIMS: :The 3'-terminal stem-loop (3'SL) of the RNA genome of the flavivirus West Nile (WNV) harbors, in its stem, one of the sequence elements that are required for genome cyclization. As cyclization is a prerequisite for the initiation of viral replication, the 3'SL was proposed to act as a replication silencer. The lower part of the 3'SL is metastable and confers a structural flexibility that may regulate the switch from the linear to the circular conformation of the viral RNA. In the human system, we previously demonstrated that a cellular RNA-binding protein, AUF1 p45, destabilizes the 3'SL, exposes the cyclization sequence, and thus promotes flaviviral genome cyclization and RNA replication. By investigating mutant RNAs with increased 3'SL stabilities, we showed the specific conformation of the metastable element to be a critical determinant of the helix-destabilizing RNA chaperone activity of AUF1 p45 and of the precision and efficiency of the AUF1 p45-supported initiation of RNA replication. Studies of stability-increasing mutant WNV replicons in human and mosquito cells revealed that the cultivation temperature considerably affected the replication efficiencies of the viral RNA variants and demonstrated the silencing effect of the 3'SL to be temperature dependent. Furthermore, we identified and characterized mosquito proteins displaying similar activities as AUF1 p45. However, as the RNA remodeling activities of the mosquito proteins were found to be considerably lower than those of the human protein, a potential cell protein-mediated destabilization of the 3'SL was suggested to be less efficient in mosquito cells. In summary, our data support a model in which the 3'SL acts as an RNA thermometer that modulates flavivirus replication during host switching.

背景与目标： : 黄病毒西尼罗河 (WNV) 的RNA基因组的3 '末端茎环 (3'SL) 在其茎中具有基因组环化所需的序列元素之一。由于环化是启动病毒复制的先决条件，因此建议3'SL用作复制消音器。3'SL的下部是亚稳态的，并具有结构灵活性，可以调节病毒RNA从线性构象到环状构象的转换。在人类系统中，我们先前证明了细胞RNA结合蛋白AUF1 p45会破坏3'SL的稳定性，暴露环化序列，从而促进黄病毒基因组环化和RNA复制。通过研究具有增加的3'SL稳定性的突变RNA，我们显示了亚稳态元件的特定构象是AUF1 p45的螺旋不稳定RNA伴侣活性以及AUF1 p45-supported启动的精度和效率的关键决定因素RNA复制。对人和蚊子细胞中稳定性提高的突变体WNV复制子的研究表明，培养温度极大地影响了病毒RNA变体的复制效率，并证明了3'SL的沉默作用是温度依赖性的。此外，我们鉴定并鉴定了具有与AUF1 p45相似活性的蚊子蛋白。然而，由于发现蚊子蛋白的RNA重塑活性远低于人类蛋白的RNA重塑活性，因此提示潜在的细胞蛋白介导的3'SL不稳定在蚊子细胞中效率较低。总之，我们的数据支持一种模型，其中3'SL充当RNA温度计，在宿主切换过程中调节黄病毒复制。

BACKGROUND & AIMS: :Larvae of Leptinotarsa decemlineata developed faster and consumed less food under short-day (Sd, 12:12 h light:darkness) than under long-day (Ld, 18:6 h L:D) conditions. The average index of food conversion efficiency was 5.4 in the Ld (25 degrees C), and 7.2 and 11.9 (at 20 and 25 degrees C, respectively) in the Sd insects. Pupae were smaller under the Ld conditions due to a greater loss of biomass during the prepupal period that was nearly twice longer than in the Sd insects. Virgin Ld females laid eggs for 6 months and survived 13 months. The lack of oviposition, reduced food intake, and behavioural changes characterised diapause in the Sd adults. Application of 100 microg JH III to newly ecdysed adults was used to probe diapause intensity. At 25 degrees C, the treatment elicited oviposition most effectively in females that were just transferred from the Ld to the Sd conditions. A distinctly lower response occurred in insects that had been kept under Sd conditions since hatching; their transfer to Ld conditions at the time of treatment had little effect on JH sensitivity. JH application to Sd females reared at 20 degrees C caused enlargement of the germaria but no eggs were formed.

背景与目标： : Leptinotarsa decemlineata的幼虫在短日 (Sd，12:12 h光: 黑暗) 下比在长日 (Ld，18:6 h L:D) 条件下发育更快，消耗更少的食物。食物转化效率的平均指数在Ld (25 ℃) 中5.4，在Sd昆虫中7.2和11.9 (分别在20和25 ℃)。在Ld条件下，p较小，这是由于在p前时期的生物量损失更大，比Sd昆虫长近两倍。处女Ld雌性产卵6个月，存活13个月。Sd成年人缺乏产卵，食物摄入减少和行为改变是滞育的特征。将100 microg JH III应用于新蜕皮的成年人，用于探测滞育强度。在25摄氏度下，该治疗最有效地在刚从Ld转移到Sd条件的雌性中引起产卵。自孵化以来一直保持在Sd条件下的昆虫的反应明显较低; 处理时它们转移到Ld条件对JH敏感性影响不大。向在20摄氏度下饲养的Sd雌性施用JH会导致germaria增大，但没有形成卵。

BACKGROUND & AIMS: :To describe the action mechanisms of Bacteriochlorin a (BCA), a second generation photosensitizer, in phosphate buffer (PB) and in dimyristoyl phosphatidylcholine (DMPC) liposomes we carried out oxygen consumption and ESR measurements. In PB, where BCA was in a monomer-dimer equilibrium, our results suggested that the oxygen consumption was related to the BCA monomers concentration in solution. Incorporation of BCA in DMPC liposomes, by promoting the monomerization of BCA, increased 9-fold the oxygen consumption in comparison to the value in PB. The use of specific singlet oxygen quenchers (Azide and 9,10-Anthracenedipropionic acid) in ESR and oxygen consumption experiments allowed us to assert that BCA was mainly a type II sensitizer when it was incorporated in DMPC. Finally, the cell survival of WiDr cells after a PDT treatment was measured for cells incubated with BCA in cell culture medium and cells incubated with BCA in DMPC. Irrespective of the dye concentration, the cell survival was lower when liposomes were used. This effect could be the result of a better BCA monomerization and/or a different BCA uptake in cells.

背景与目标： : 为了描述第二代光敏剂细菌氯蛋白a (BCA) 在磷酸盐缓冲液 (PB) 和二肉豆蔻酰磷脂酰胆碱 (DMPC) 脂质体中的作用机理，我们进行了耗氧量和ESR测量。在PB中，BCA处于单体-二聚体平衡状态，我们的结果表明，耗氧量与溶液中BCA单体的浓度有关。通过促进BCA的单体化，将BCA掺入DMPC脂质体中，与PB相比，氧消耗增加了9倍。在ESR和耗氧实验中使用特定的单线态氧猝剂 (叠氮化物和9,10-蒽二丙酸) 使我们可以断言，当BCA掺入DMPC中时，BCA主要是II型敏化剂。最后，对于在细胞培养基中与BCA孵育的细胞和在DMPC中与BCA孵育的细胞，测量PDT处理后WiDr细胞的细胞存活率。无论染料浓度如何，使用脂质体时细胞存活率较低。这种效果可能是更好的BCA单体化和/或细胞中不同的BCA摄取的结果。