BACKGROUND & AIMS: :Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.

背景与目标： ：Protein通常以二进制方式分类为结构化或无序。但是，这种方法存在一些缺陷。首先，蛋白质折叠总是以物理化学环境为条件。在某些情况下结构化的蛋白质在其他情况下会变得无序。其次，它掩盖了行为的基本不对称性。虽然所有结构化蛋白质都可以通过环境变化来展开，但并非所有无序蛋白质都具有折叠能力。无法适应这些复杂性会混淆蛋白质结构域和内在无序区域的定义。我们通过对腮腺炎病毒及其近亲的RNA聚合酶绘制的一系列小结合域的实验研究说明了这些观点。按面值评估，这些域位于结构连续体上，具有折叠，部分折叠和接近非结构化的成员。然而，该家族中存在的病症是有条件的，并且这些紧密相关的多肽可以在适当的条件下进入相同的折叠状态。强调构象稳定性的蛋白质结构域的任何启发式定义都将该结构域家族分为两部分，这是没有生物学意义的。结构域可以采用特定的三级结构的能力来更好地定义：根据情况，该结构可能会实现，也可能不会实现。这明确地允许蛋白质折叠的条件性质，并且更清楚地从可能无折叠而起作用的内在无序的区域划定结构域。

BACKGROUND & AIMS: :In his commentary on Varni et al.'s (Qual Life Res. doi: 10.1007/s11136-013-0370-4 , 2013) article, McIntosh (Qual Life Res. doi: 10.1007/s11136-013-0465-y , 2013) has two main arguments. First, we should have paid more attention to statistical tests (i.e., χ 2 values) instead of approximate fit indexes for our analysis, especially with the baseline model. Second, Bayesian methods are better than the frequentist methods we used in determining the model's invariance across age and gender groups. We believe that statistical tests do have a place in assessing model fit, but overemphasis on them, especially with larger sample sizes, can lead to errant decisions. Second, while we agree that Bayesian methods have the potential to contribute much to the field of assessing invariance, more development needs to be conducted before they can be widely utilized in assessing factorial invariance across groups.

背景与目标： ：在对Varni等人（Qual Life Res。doi：10.1007 / s11136-013-0370-4，2013）文章的评论中，McIntosh（Qual Life Res。doi：10.1007 / s11136-013-0465-y， 2013年）有两个主要论点。首先，我们应该更加重视统计检验（即χ2值），而不是近似拟合指标来进行分析，尤其是对于基线模型。其次，贝叶斯方法要比我们用来确定模型在年龄和性别组中的不变性的常用方法更好。我们认为统计测试确实可以在评估模型拟合度中占有一席之地，但是过分强调它们（尤其是在样本量较大的情况下）可能会导致错误的决策。其次，虽然我们同意贝叶斯方法有可能在评估不变性方面做出很大贡献，但在将其广泛用于评估各组的因式不变性之前，还需要进行更多的开发。

BACKGROUND & AIMS: :Cooperation declines in repeated public good games because individuals behave as conditional cooperators. This is because individuals imitate the social behaviour of successful individuals when their payoff information is available. However, in human societies, individuals cooperate in many situations involving social dilemmas. We hypothesize that humans are sensitive to both success (payoffs) and how that success was obtained, by cheating (not socially sanctioned) or good behaviour (socially sanctioned and adds to prestige or reputation), when information is available about payoffs and prestige. We propose and model a repeated public good game with heterogeneous conditional cooperators where an agent's donation in a public goods game depends on comparing the number of donations in the population in the previous round and with the agent's arbitrary chosen conditional cooperative criterion. Such individuals imitate the social behaviour of role models based on their payoffs and prestige. The dependence is modelled by two population-level parameters: affinity towards payoff and affinity towards prestige. These affinities influence the degree to which agents value the payoff and prestige of role models. Agents update their conditional strategies by considering both parameters. The simulations in this study show that high levels of cooperation are established in a population consisting of heterogeneous conditional cooperators for a certain range of affinity parameters in repeated public good games. The results show that social value (prestige) is important in establishing cooperation.

背景与目标： ：在反复的公益活动中，合作减少了，因为个人表现为有条件的合作者。这是因为，当可获得他们的回报信息时，个人会模仿成功人士的社交行为。但是，在人类社会中，个人在许多涉及社会困境的情况下进行合作。我们假设人们对成功（收益）以及成功与否（无论是通过作弊（未受到社会制裁）还是良好行为（受到社会认可并会增加声望或声誉））都非常敏感，只要他们可以获得有关收益和声望的信息。我们提出了一个具有异类条件合作者的重复公共物品博弈并对其进行建模，其中代理在公共物品博弈中的捐赠取决于将前一轮中人口捐赠的数量与代理的任意选择的条件合作标准进行比较。这些人根据他们的回报和声望来模仿榜样的社会行为。依赖关系由两个总体级别的参数建模：对收益的亲和力和对声望的亲和力。这些亲和力会影响代理人重视榜样的回报和声望的程度。代理通过考虑两个参数来更新其条件策略。本研究中的模拟显示，在重复的公益游戏中，对于特定范围的亲和力参数，在由异质条件合作者组成的群体中建立了高水平的合作。结果表明，社会价值（信誉）在建立合作中很重要。

BACKGROUND & AIMS: :Fe-Mn-C-Al alloy is a new steel grade of TWIP steel developed in recent years. It has an excellent combination of elongation and tensile strength, as well as good anti-delayed fracture property. However, the crack sensitivity of this new TWIP steel has not been reported yet. In this study, differential thermal analysis (DTA) method was used, combined with professional thermodynamic software ThermoCalc to analyze the solidification behavior for Fe-Mn-C-Al alloys with different chemical compositions. Based on this, the crack sensitivity of TWIP steel is further determined. Through this study, it was found that Fe-Mn-C-Al TWIP steel may have a solidification sequence with high crack sensitivity, belonging to hypo-peritectic steel. Moreover, it was found that the carbon content has a large influence on the solidification behavior, and the manganese content also affects the solidification sequence. It can make the phase transition sequence of the solidification process change significantly, which may avoid the solidification behavior of hypo-peritectic reaction. The analysis results by thermodynamic software ThermoCalc are in good agreement with the experimental results. It displays thermoCalc can be a cost-effective way to develop Fe-Mn-C-Al TWIP steel. It is of great significance for shortening the development period of new Fe-Mn-C-Al steel grades.

背景与目标： ：Fe-Mn-C-Al合金是近年来开发的TWIP钢的新钢种。它具有优异的伸长率和拉伸强度组合，以及良好的抗延迟断裂性能。但是，尚未报道这种新的TWIP钢的裂纹敏感性。在这项研究中，使用差热分析（​​DTA）方法，结合专业的热力学软件ThermoCalc分析具有不同化学成分的Fe-Mn-C-Al合金的凝固行为。基于此，进一步确定了TWIP钢的裂纹敏感性。通过这项研究，发现Fe-Mn-C-Al TWIP钢可能具有高裂纹敏感性的凝固序列，属于低晶包晶钢。此外，发现碳含量对凝固行为具有很大的影响，并且锰含量也影响凝固顺序。它可以使凝固过程的相变顺序发生显着变化，从而可以避免低包晶反应的凝固行为。热力学软件ThermoCalc的分析结果与实验结果吻合良好。它显示thermoCalc是开发Fe-Mn-C-Al TWIP钢的一种经济有效的方式。对于缩短新型Fe-Mn-C-Al钢的开发周期具有重要意义。

BACKGROUND & AIMS: :Change in References list order. [...].

背景与目标： ：更改参考列表的顺序。 [...]。

BACKGROUND & AIMS: OBJECTIVES:The aim of this study was to derive longitudinal reference values of fetal growth (estimated fetal weight [EFW] and abdominal circumference [AC]) during the third trimester and to develop coefficients for conditional growth assessment. PATIENTS AND METHODS:A prospective cohort study was conducted involving consecutive singleton pregnancies in a low-risk population for a routine third-trimester scan at 30+0-34+6 weeks and follow-up at 37+0-38+6 weeks for an additional ultrasound. Statistical analysis was based on multilevel modeling using MLwiN software. Unconditional centiles were calculated from z-values at each gestational age, and conditional centiles were calculated from z-values at a given measurement (30-34 weeks) and the expected measurement (37-38 weeks). RESULTS:At 30-34 weeks, 8 and 9.3% of the fetuses had an unconditional EFW below the 10th and above the 90th centile, respectively. At 37-38 weeks, these figures were 10.3 and 9.3%, respectively. Regarding the unconditional AC, at the first scan, 8.9 and 9.6% had values below the 10th and above the 90th centile, while at the second scan 10.5 and 10.5% had values below the 10th and above the 90th centile, respectively. The proportion with a conditional EFW below the 10th and above the 90th centile was 10.2 and 9.4% at the second scan, respectively. For conditional AC, these figures were 10.7 and 10.3%, respectively. CONCLUSION:We have produced reference centiles for EFW and AC growth during the third trimester as a useful tool for quantifying growth.

背景与目标： 目的：本研究的目的是得出妊娠中期胎儿生长的纵向参考值（估计的胎儿体重[EFW]和腹围[AC]），并建立条件生长评估的系数。
患者和方法：进行了一项前瞻性队列研究，涉及低危人群中连续单胎妊娠，在30 0-34 6周进行常规的孕中期扫描，并在37 0-38 6周进行随访，以进行额外的超声检查。统计分析基于使用MLwiN软件的多级建模。根据每个胎龄的z值计算无条件的百分位数，根据给定的测量值（30-34周）和预期的测量值（37-38周）的z值计算条件的百分位。
结果：在30-34周时，分别有8％和9.3％的胎儿在第10个百分位以下和第90个百分位以上有无条件的EFW。在第37-38周时，这些数字分别为10.3和9.3％。对于无条件AC，在第一次扫描时，8.9和9.6％的值低于第10个百分位，在第90个百分点之上，而在第二次扫描中，10.5和10.5％的值分别在第10个百分位数和第90个百分率以上。在第二次扫描时，条件EFW低于第10个百分位和高于第90个百分位的比例分别为10.2％和9.4％。对于有条件的AC，这些数字分别为10.7％和10.3％。
结论：我们为妊娠晚期的EFW和AC增长绘制了参考百分位，作为量化增长的有用工具。

BACKGROUND & AIMS: :1. The strain M 5 al of Klebsiella pneumoniae grows excellently with starches. We were able to show that besides the pullulanase associated with the external membrane of the cells the bacterium produces an inducible, extracellular cyclodextrin glucanotransferase [1,4-alpha-D-glucan-4-alpha-(1,4-alpha-glucano)-transferase (cyclising) (EC 2.4.1.19)]. Potato starch and cyclohexaamylose or cycloheptaamylose were found to be the best "inducing" carbon sources for the synthesis of the enzyme. When the bacteria are grown batchwise, maltose is a poorly "inducing" carbon source; larger quantities of the enzyme are synthesized by continuous cultivation with maltose as growth limiting factor. 2. For the determination of the cyclodextrin glucanotransferase-activity an assay method wsa worked out. 3. The enzyme could be separated from the culture filtrate and purified to more than 90% in few steps. At a total yield of 61.2% related to the activity of the culture filtrate employed we received an enzyme solution with the specific activity of 26.6 units/mg protein. Some properties of the enzyme are described. 4. The products formed from amylopectin by the enzyme were analyzed. Somewhat more than half the amylopectin was found as cyclodextrins. 29.3% of the cyclodextrin fraction were cycloheptaamylose, 47.2% cyclohexaamylose and 10.7% exo-branched cyclohexaamylose. 12.8% of cyclohexaamylose were obtained from a cyclodextrin glucanotransferase-limit dextrin after debranching by pullulanase and exposing the product to the action of the glucanotransferase again. 5. The importance of the cyclodextrin glucanotransferase for the utilization of starches by this strain of Klebsiella pneumoniae is discussed. After a first characterization the enzyme is compared to the amylase of Bacillus macerans.

背景与目标： ：1。肺炎克雷伯菌的菌株M 5 al与淀粉一起生长良好。我们能够证明，除与细胞外膜相关的支链淀粉酶外，细菌还产生诱导型胞外环糊精葡聚糖转移酶[1,4-α-D-葡聚糖-4-α-（1,4-α-葡聚糖） -转移酶（环化）（EC 2.4.1.19）]。发现马铃薯淀粉和环己淀粉或环庚淀粉是合成该酶的最佳“诱导”碳源。当细菌分批生长时，麦芽糖是不良的“诱导”碳源。通过以麦芽糖为生长限制因子的连续培养来合成大量的酶。 2.为了测定环糊精的葡糖基转移酶活性，制定了一种测定方法。 3.可以从培养滤液中分离出酶，并通过几个步骤将其纯化至90％以上。与所使用的培养滤液的活性有关的总产率为61.2％，我们获得了比活性为26.6单位/ mg蛋白质的酶溶液。描述了酶的一些特性。 4.分析了由支链淀粉通过酶形成的产物。发现大约一半以上的支链淀粉是环糊精。 29.3％的环糊精级分是环庚直链淀粉，47.2％的环己直链淀粉和10.7％的外分支支化的环己直链淀粉。在通过支链淀粉酶脱支并且使产物再次暴露于葡聚糖转移酶的作用之后，从环糊精葡聚糖转移酶-极限糊精中获得12.8％的环己糖。 5.讨论了环糊精葡聚糖转移酶对于该肺炎克雷伯氏菌菌株利用淀粉的重要性。在首次鉴定后，将该酶与马氏芽孢杆菌的淀粉酶进行比较。

BACKGROUND & AIMS: :Buck and Duffy (1980) and Borod et al. (1985) found evidence of deficits in spontaneous expressiveness in right brain-damaged (RBD) patients relative to LBD patients and controls. Using FACS, Mammucari et al. (1988) failed to replicate this result and questioned our methods and findings. This paper replies (a) that Mammucari et al. (1988)'s review of our work is selective and misleading; (b) that there are aspects of their study that can account for their null results, including the insufficient sensitivity of FACS for the measurement of spontaneous expressiveness; and (c) that the results of Mammucari et al. (1988) regarding "aversive eye movements" to a negative film in LBD and control, but not RBD, patients are in fact compatible with our findings. This paper also suggests a general strategy for the objective and comprehensive analysis of spontaneous emotional expressiveness.

背景与目标： ：Buck and Duffy（1980）和Borod等。 （1985年）发现相对于LBD患者和对照组，右脑损伤（RBD）患者自发性表达缺乏的证据。 Mammucari等人使用FACS。 （1988）未能复制这个结果，并质疑我们的方法和发现。本文答复（a）Mammucari等。 （1988）对我们工作的评论是有选择性和误导性的； （b）他们研究的某些方面可以解释其无效的结果，包括流式细胞仪对自发表达能力的敏感性不足； （c）Mammucari等人的结果。 （1988年）关于在LBD和对照组（而非RBD）中使负片“平均眼球运动”，患者实际上与我们的发现相符。本文还提出了一种客观和全面分析自发情绪表达能力的一般策略。

BACKGROUND & AIMS: :The International Physical Activity Questionnaire (IPAQ) has been widely used to assess physical activity in healthy populations. The present study compared physical activity assessed by the long, self-administrated version of the International Physical Activity Questionnaire with physical activity assessed by accelerometry in patients with fibromyalgia. A total of 99 (five men) participants with fibromyalgia completed the International Physical Activity Questionnaire and wore an accelerometer for nine consecutive days. We analysed the correlations of physical activity expressed as min · day(-1) of light, moderate, vigorous, and moderate to vigorous (MVPA) intensity, as well as time spent sitting, by the International Physical Activity Questionnaire and accelerometry by Spearman correlations. Bland and Altman plots were performed to verify the agreements between both instruments. The results showed weak yet significant correlations (Rs = 0.15-0.39, all P < 0.05) in all physical activity intensities between the two instruments, except for sedentary time. The highest correlations were observed for physical activity at home or in garden (Rs = 0.297, P < 0.01). The results suggest that the long self-administrated International Physical Activity Questionnaire is a questionable instrument to assess physical activity in patients with fibromyalgia. Therefore, physical activity measurement in fibromyalgia patients should not be limited solely to self-reported measures.

背景与目标： ：国际体育锻炼问卷（IPAQ）已被广泛用于评估健康人群的体育锻炼。本研究比较了通过长期自我管理的《国际体力活动问卷》评估的体力活动与通过加速计评估的纤维肌痛患者的体力活动。共有99名（五名男性）纤维肌痛参与者参加了《国际体育锻炼问卷》，并连续9天佩戴了加速度计。我们通过国际体育活动问卷和Spearman相关性分析了表示为轻度，中度，剧烈和中度至剧烈（MVPA）强度的min·day（-1）的体育活动的相关性，以及坐着花费的时间。 。进行了Bland和Altman绘图以验证两种仪器之间的一致性。结果表明，除了久坐时间外，两种器械之间所有身体活动强度之间的相关性均较弱（Rs = 0.15-0.39，所有P <0.05）。在家中或花园里进行体育锻炼的相关性最高（Rs = 0.297，P <0.01）。结果表明，长期自我管理的《国际身体活动量表》是评估纤维肌痛患者身体活动量的可疑工具。因此，纤维肌痛患者的身体活动测量不应仅局限于自我报告的测量。

BACKGROUND & AIMS: :The authors wish to make a correction to Section 2 [...].

背景与目标： ：作者希望对第2节[...]进行更正。

BACKGROUND & AIMS: OBJECTIVE:To investigate the functions of Fibroblast Growth Factor Receptor-2 (FGFR2) at different stages of cell differentiation. The engineered murine embryonic stem (ES) cells with conditional knockout of FGFR2 were developed depending on Cre-loxP. METHODS:Cre-loxP system was used in a conditional targeting vector. The competent AM-1 bacteria, which expressed Cre-recombinase, was used to confirm the Cre-mediated deletion of the floxed exons 7 and 8 of FGFR2. The targeting vector was electroporated into the ES cells, and the transfected ES cells were screened with G418 and Ganciclovir. Finally, the ES clones with correct targeting events were identified by Southern Blot and PCR. RESULTS:The targeting vector with conditional knockout of murine FGFR2 was successfully constructed and confirmed by PCR and digestion analysis in bacteria. 86 ES clones were collected by selective culture with G418 and Ganciclovir. Four of the 86 ES clones were found containing the targeting gene sequence in genomic DNA proved by Southern Blot with a 5'-end flank probe. Two of the four ES clones had the correct targeting events that included the insertion of the targeting gene sequence in genomic DNA and were checked by Southern Blot with a 3'-end flanking probe. Finally, the insertion of loxP (loxP3) between exons 8 and 9 in genomic DNA was identified in one of the two ES clones by Southern Blot and PCR. CONCLUSION:FGFR2 conditional knockout depending on Cre-loxP can be successfully used in ES cells.

背景与目标： 目的：探讨成纤维细胞生长因子受体2（FGFR2）在不同分化阶段的功能。根据Cre-loxP，开发了具有条件敲除FGFR2的工程鼠胚胎干（ES）细胞。
方法：将Cre-loxP系统用于条件靶向载体。表达Cre重组酶的感受态AM-1细菌用于确认Cre介导的FGFR2外显子7和8的缺失。将靶向载体电穿孔到ES细胞中，并用G418和更昔洛韦筛选转染的ES细胞。最后，通过Southern印迹和PCR鉴定具有正确靶向事件的ES克隆。
结果：成功构建了有条件敲除鼠FGFR2的靶向载体，并通过PCR和酶切分析鉴定。通过用G418和更昔洛韦选择性培养收集了86个ES克隆。发现86个ES克隆中有四个在基因组DNA中包含靶向基因序列，该DNA由Southern Blot用5'端侧翼探针证实。四个ES克隆中的两个具有正确的靶向事件，包括在基因组DNA中插入了靶向基因序列，并使用3'端侧翼探针通过Southern Blot检测。最后，通过Southern印迹和PCR在两个ES克隆之一中鉴定出loxP（loxP3）在基因组DNA的外显子8和9之间的插入。
结论：依赖于Cre-loxP的FGFR2条件敲除可成功用于ES细胞。

BACKGROUND & AIMS: :A recent publication in Biophysical Journal by Bianco et al. ("Interaction forces between F-actin and titin PEVK domain measured with optical tweezers") shows that the PEVK domain of titin molecules interacts with F-actin. This newly discovered behavior could influence the mechanical properties of striated muscles, and Bianco et al. suggest that the interactions between actin and titin could modulate thixotropic behavior. In this Comment to the Editor, we suggest that the thixotropic properties of striated muscles in vivo are more likely to reflect dynamic changes in the proportion of myosin cross-bridges bound between the myofilaments.

背景与目标： ：Bianco等人在《生物物理杂志》上的最新出版物。 （“用光镊测量的F-肌动蛋白和肌动蛋白PEVK结构域之间的相互作用力”）表明，肌动蛋白分子的PEVK结构域与F-肌动蛋白相互作用。这种新发现的行为可能会影响横纹肌的机械性能，Bianco等人。提示肌动蛋白和肌动蛋白之间的相互作用可以调节触变行为。在此给编辑的评论中，我们建议体内横纹肌的触变特性更可能反映出肌丝之间束缚的肌球蛋白横桥比例的动态变化。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :G protein-coupled receptors (GPCRs) coupled to activation of Gs, such as the PTH1 receptor (PTH1R), have long been known to regulate skeletal function and homeostasis. However, the role of GPCRs coupled to other G proteins such as Gi is not well established. We used the tet-off system to regulate the expression of an activated Gi-coupled GPCR (Ro1) in osteoblasts in vivo. Skeletal phenotypes were assessed in mice expressing Ro1 from conception, from late stages of embryogenesis, and after weaning. Long bones were assessed histologically and by microcomputed tomography. Expression of Ro1 from conception resulted in neonatal lethality that was associated with reduced bone mineralization. Expression of Ro1 starting at late embryogenesis resulted in a severe trabecular bone deficit at 12 wk of age (>51% reduction in trabecular bone volume fraction in the proximal tibia compared with sex-matched control littermates; n = 11; P < 0.01). Ro1 expression for 8 wk beginning at 4 wk of age resulted in a more than 20% reduction in trabecular bone volume fraction compared with sex-matched control littermates (n = 16; P < 0.01). Bone histomorphometry revealed that Ro1 expression is associated with reduced rates of bone formation and mineral apposition without a significant change in osteoblast or osteoclast surface. Our results indicate that signaling by a Gi-coupled GPCR in osteoblasts leads to osteopenia resulting from a reduction in trabecular bone formation. The severity of the phenotype is related to the timing and duration of Ro1 expression during growth and development. The skeletal phenotype in Ro1 mice bears some similarity to that produced by knockout of Gs-alpha expression in osteoblasts and thus may be due at least in part to Gi-mediated inhibition of adenylyl cyclase.

背景与目标： 长期以来，已知与Gs激活偶联的：G蛋白偶联受体（GPCR）可调节骨骼功能和体内平衡。但是，与其他G蛋白（例如Gi）偶联的GPCR的作用尚不明确。我们使用tet-off系统来调节体内成骨细胞中激活的Gi偶联GPCR（Ro1）的表达。从受孕，胚胎发生的后期以及断奶后评估表达Ro1的小鼠的骨骼表型。通过组织学和微计算机断层扫描对长骨进行评估。从受孕中表达Ro1会导致新生儿致死性，这与减少的骨矿化有关。 Ro1的表达始于胚胎晚期，导致在12周龄时出现严重的小梁骨缺损（胫骨近端的小梁骨体积分数与性别匹配的对照同窝仔相比减少了51％以上； n = 11； P <0.01）。与性别匹配的对照同窝仔相比，从4周龄开始的8周Ro1表达导致小梁骨体积分数减少了20％以上（n = 16； P <0.01）。骨组织形态计量学表明，Ro1表达与成骨率和矿物质沉积率降低相关，而成骨细胞或破骨细胞表面无明显变化。我们的结果表明，成骨细胞中通过Gi偶联GPCR进行的信号传导导致骨小梁减少，其原因是小梁骨形成减少。表型的严重性与Ro1表达在生长发育过程中的时机和持续时间有关。 Ro1小鼠的骨骼表型与成骨细胞中Gs-α表达的敲除产生的相似，因此可能至少部分是由于Gi介导的对腺苷酸环化酶的抑制。

BACKGROUND & AIMS: :Hippocampal CA1 pyramidal neurons are normally quiescent but can fire spontaneously when stimulated by muscarinic agonists. In brain slice recordings from mouse CA1 pyramidal neurons, we examined the ionic basis of this activity using interleaved current-clamp and voltage-clamp experiments. Both in control and after muscarinic stimulation, the steady-state current-voltage curve was dominated by inward TTX-sensitive persistent sodium current (I(NaP)) that activated near -75 mV and increased steeply with depolarization. In control, total membrane current was net outward (hyperpolarizing) near -70 mV so that cells had a stable resting potential. Muscarinic stimulation activated a small nonselective cation current so that total membrane current near -70 mV shifted to become barely net inward (depolarizing). The small depolarization triggers regenerative activation of I(NaP), which then depolarizes the cell from -70 mV to spike threshold. We quantified the relative contributions of I(NaP), hyperpolarization-activated cation current (I(h)), and calcium current to pacemaking by using the cell's own firing as a voltage command along with specific blockers. TTX-sensitive sodium current was substantial throughout the entire interspike interval, increasing as the membrane potential approached threshold, while both Ih and calcium current were minimal. Thus, spontaneous activity is driven primarily by activation of I(NaP) in a positive feedback loop starting near -70 mV and providing increasing inward current to threshold. These results show that the pacemaking "engine" from I(NaP) is an inherent property of CA1 pyramidal neurons that can be engaged or disengaged by small shifts in net membrane current near -70 mV, as by muscarinic stimulation.

背景与目标： ：海马CA1锥体神经元通常是静止的，但在受到毒蕈碱激动剂刺激时会自发放电。在小鼠CA1锥体神经元的脑切片记录中，我们使用交错的电流钳和电压钳实验检查了这种活动的离子基础。在对照和毒蕈碱刺激后，稳态电流-电压曲线都由向内TTX敏感的持续钠电流（I（NaP））控制，该电流在-75 mV附近激活，并随着去极化而急剧增加。在对照中，总膜电流在-70 mV附近呈净向外（超极化）状态，因此细胞具有稳定的静息电位。毒蕈碱刺激激活了一个小的非选择性阳离子电流，因此-70 mV附近的总膜电流发生了移动，几乎变为净净向内（去极化）。小的去极化触发I（NaP）的再生激活，然后使细胞从-70 mV极化到尖峰阈值。我们通过使用电池自身的放电作为电压指令以及特定的阻滞剂，量化了I（NaP），超极化激活阳离子电流（I（h））和钙电流对起搏的相对贡献。对TTX敏感的钠电流在整个尖峰间隔期间都很大，随着膜电位接近阈值而增加，而Ih和钙电流均最小。因此，自发活动主要由激活正反馈回路中的I（NaP）驱动，该正反馈回路开始于-70 mV并提供增加的内向电流至阈值。这些结果表明，来自I（NaP）的起搏“引擎”是CA1锥体神经元的固有特性，可以通过毒蕈碱刺激使接近-70 mV的净膜电流发生微小变化而参与或脱离。