BACKGROUND & AIMS: :Candida parapsilosis is an important cause of candidiasis, yet few molecular tools are available. We adapted a recyclable nourseothricin resistance marker gene (SAT1) originally developed for use with C. albicans in order to generate gene knockouts from C. parapsilosis. We first replaced the promoters driving expression of the FLP recombinase and the SAT1 genes with the equivalent sequences from C. parapsilosis. We then used the cassette to generate a homozygous knockout of C. parapsilosis URA3. The ura3 knockouts have altered colony morphologies. We also knocked out both alleles of an ortholog of BCR1, a gene encoding a transcription factor known to be required for biofilm development in C. albicans. We show that C. parapsilosis BCR1 is necessary for biofilm development in C. parapsilosis and for expression of the cell wall protein encoded by RBT1. Our results suggest that there are significant similarities in the regulation of biofilms between the two species, despite the fact that C. parapsilosis does not generate true hyphae and that BCR1 regulates the expression of many hypha-specific adhesins in C. albicans.

背景与目标： 念珠菌：念珠菌是念珠菌病的重要病因，但分子工具很少。我们调整了最初为白念珠菌而开发的可回收的神经丝菌素抗性标记基因（SAT1），以便从副念珠菌中产生基因敲除。我们首先用来自C. parapsilosis的等效序列替换了驱动FLP重组酶和SAT1基因表达的启动子。然后，我们使用盒式磁带产生了C. parapsilosis URA3的纯合敲除。 ura3基因敲除改变了菌落的形态。我们还敲除了BCR1直系同源基因的两个等位基因，BCR1是编码白色念珠菌生物膜发育所需的转录因子的基因。我们表明，C。parapsilosis BCR1是必要的生物膜发育在C. parapsilosis和由RBT1编码的细胞壁蛋白的表达。我们的研究结果表明，尽管事实上副寄生念珠菌并没有产生真正的菌丝，而BCR1调节了白色念珠菌中许多菌丝特异性粘附素的表达，但两种物种在生物膜的调控上却存在着显着的相似之处。

BACKGROUND & AIMS: OBJECTIVES:To investigate which characteristics of women and healthcare professionals (HCPs) were associated with changing to another combined hormonal contraceptive (CHC) method after contraceptive counselling. METHODS:CHOICE was a cross-sectional survey in which 18,787 women were counselled about combined hormonal contraceptives, during which their contraceptive methods preferred both prior to and after counselling were recorded. In this subanalysis, characteristics associated with changing the method after counselling were determined using logistic regression models. RESULTS:The probability of intending to change from the pill to another method was associated with being older; university-educated; being in a steady relationship; a prior unintended pregnancy; a younger HCP or one who recommended methods other than the pill. Changing to the patch was associated with a female HCP or a HCP who recommended the patch or an injectable. Changing to the ring was associated with being over 21 years; university-educated; being in a relationship; previous hormonal method use; and counselling by a female HCP, a HCP < 60 years old, or a HCP who recommended the ring or an implant. The country of residence influenced these changes in a complex pattern. CONCLUSIONS:Women's choice of CHC methods after contraceptive counselling are influenced by their age, educational background, relationship status, prior unplanned pregnancies and country of residence, as well as age, gender and preferences of their HCP.

背景与目标： 目的：调查在避孕咨询后，女性和医护人员（HCP）的哪些特征与改用另一种联合激素避孕（CHC）方法有关。
方法：选择是一项横断面调查，其中向18,787名妇女提供了有关联合激素避孕药的咨询，在此期间，记录了她们在咨询之前和之后首选的避孕方法。在此子分析中，使用逻辑回归模型确定与咨询后更改方法有关的特征。
结果：打算从药丸换成另一种方法的可能性与年纪大有关。受过大学教育；保持稳定的关系；先前的意外怀孕；较年轻的HCP或建议使用除药丸以外的方法的人。更换贴剂与女性HCP或推荐贴剂或注射剂的HCP有关。更换戒指的年龄超过21岁。受过大学教育；处于恋爱关系中；以前使用过的荷尔蒙方法；并由女性HCP，小于60岁的HCP或推荐环或植入物的HCP进行咨询。居住国以复杂的方式影响了这些变化。
结论：避孕咨询后，妇女选择慢性丙型肝炎的方法受到其年龄，教育背景，人际关系，先前计划外的怀孕和居住国家，年龄，性别和他们的HCP偏好的影响。

BACKGROUND & AIMS: BACKGROUND:We previously demonstrated angiotensin converting enzymes (ACE) over-expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I) treatment reduced colitis severity in this model. However, ACE-I has not been tested in more immunologically relevant colitis models. AIM:We hypothesized that ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model. METHODS:Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.) for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg for 21 days. Prednisolone (PSL) with or without enalaprilat were used as therapeutic, comparative groups. All groups were compared to a placebo treated group. Outcome measures were clinical course, histology, abundance of pro-inflammatory cytokines/chemokines, and epithelial barrier function. RESULTS:Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL: 85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups showed significantly better histological scores versus placebo mice. ACE-I and the PSL groups significantly reduced several pro-inflammatory cytokines versus placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I groups. Blood pressure was not affected in ACE-I treated mice compared to placebo mice. CONCLUSIONS:ACE-I was effective in reducing severity of colitis in an IL-10-/- model. The addition of prednisolone minimally augmented this effect. The findings suggest that appropriately dosed ACE-I with or without steroids may be a new therapeutic agent for colitis.

背景与目标： 背景：我们先前证明了在葡聚糖-硫酸钠结肠炎模型中血管紧张素转化酶（ACE）的过度表达。在该模型中，ACEI（ACE-I）抑制剂治疗可降低结肠炎的严重程度。但是，尚未在更具免疫学意义的结肠炎模型中测试ACE-1。
目的：我们假设ACE-1可以降低IL-10基因敲除（-/-）结肠炎模型中的疾病严重程度。
方法：通过给予10周龄的IL-10-/-小鼠吡罗昔康（P.O.）14天来诱发结肠炎。 ACE-1依那普利拉经鼻给药，剂量为6.25 mg / kg，持续21天。泼尼松龙（PSL）有或没有恩那普利拉被用作治疗性比较组。将所有组与安慰剂治疗组进行比较。结果指标包括临床病程，组织学，促炎细胞因子/趋化因子的含量以及上皮屏障功能。
结果：依那普利拉的生存率（91％）优于其他治疗组（PSL：85.7％，PSL ACE-1：71.4％，安慰剂：66.6％）。与安慰剂小鼠相比，ACE-1和PSL ACE-1组的组织学评分明显更高。与安慰剂小鼠相比，ACE-1和PSL组显着减少了几种促炎性细胞因子。在ACE-I和PSL ACE-I组中，FITC-葡聚糖的通透性降低。与安慰剂小鼠相比，ACE-1治疗的小鼠的血压没有受到影响。
结论：ACE-1在降低IL-10-/-模型中结肠炎的严重程度方面有效。泼尼松龙的添加最小程度地增强了这种作用。研究结果表明，适当剂量的ACE-I与或不与类固醇激素可能是结肠炎的一种新的治疗剂。

BACKGROUND & AIMS: BACKGROUND:An impairment of the intestinal barrier function is one of the major characteristics of Crohn's disease (CD). This study aimed to evaluate the impact of autophagy induction by rapamycin on the intestinal epithelial barrier function in CD model mice. METHODS:IL-10 knockout (IL-10 KO) mice were used as the human CD models in this study. All the mice were randomly assigned into four groups, (a) wild-type (WT) group; (b) IL-10 KO group; (c) IL-10 KO + rapamycin group and (d) IL-10 KO + 3-methyladenine (3-MA), containing 6 mice in each group. The disease activity index (DAI), histology, pro-inflammatory cytokines and chemotactic factors in colon tissues, intestinal and colonic permeability, distributions and expressions of tight junction (TJ) proteins, epithelial apoptosis of mice in four groups were evaluated and compared. RESULTS:Autophagy induction by rapamycin treatment ameliorated DAI and histological colitis, decreased pro-inflammatory cytokines (TNF-α, IFN-γ and IL-17) and chemotactic factors (CXCL-1 and CXCL-2), decreased intestinal and colonic permeability, improved the distribution and expression of TJ proteins in IL-10 KO mice. CONCLUSION:Autophagy induction by rapamycin significantly improved intestinal barrier function and protected IL-10 KO mice from the experimental chronic colitis.

背景与目标： 背景：肠道屏障功能的损害是克罗恩病（CD）的主要特征之一。这项研究旨在评估雷帕霉素诱导的自噬对CD模型小鼠肠上皮屏障功能的影响。
方法：以IL-10基因敲除小鼠（IL-10 KO）作为人类CD模型。将所有小鼠随机分为四组，（a）野生型（WT）组；（b）野生型（WT）组。 （b）IL-10 KO组； （c）IL-10 KO雷帕霉素组和（d）IL-10 KO 3-甲基腺嘌呤（3-MA），每组6只小鼠。评估并比较了四组小鼠的疾病活动指数（DAI），组织学，结肠组织中的促炎细胞因子和趋化因子，肠和结肠通透性，紧密连接（TJ）蛋白的分布和表达，小鼠上皮细胞凋亡。
结果：雷帕霉素诱导的自噬改善了DAI和组织性结肠炎，降低了促炎细胞因子（TNF-α，IFN-γ和IL-17）和趋化因子（CXCL-1和CXCL-2），降低了肠道和结肠的通透性，改善了IL-10 KO小鼠中TJ蛋白的分布和表达。
结论：雷帕霉素自噬诱导显着改善肠屏障功能，并保护IL-10 KO小鼠免受实验性慢性结肠炎的侵害。

BACKGROUND & AIMS: :Classically, it has been thought that high-affinity nicotinic receptors-containing beta2 subunits are the most important receptor subtypes for nicotinic involvement in cognitive function and nicotine self-administration, while low affinity alpha7-containing nicotinic receptors have not been thought to be important. In the current study, we found that knockout of either beta2 or alpha7 subunits caused significant deficits in spatial discrimination in mice. The character of the impairment in the two knockouts was different. The beta2 knockout preferentially impaired cognition in males while the alpha7 caused impairment regardless of sex. Both beta2- and alpha7-containing nicotinic receptors also are important for nicotine self-administration, also in different ways. Most animal model studies of nicotine self-administration are relatively short-term whereas the problem of tobacco addiction is considerably longer-term. To better model the impact of nicotinic receptor subtypes on nicotine self-administration over the long-term, we studied the impact of genetic knockout of low affinity alpha7 receptors vs. high-affinity beta2-containing nicotinic receptors. Mice with knockouts of either of these receptors and their wildtype counter parts were given free access to a choice of nicotine-containing and nicotine-free solution in their home cages on a continuous basis over a period of 5 months. During the first few weeks, the beta2-containing nicotinic receptor knockout mice showed a significant decrease in nicotine consumption relative to wildtype mice, whereas the alpha7 knockout mice did not significantly differ from wildtype controls at the beginning of their access to nicotine. Interestingly, in the longer-term after the first few weeks of nicotine access, the beta2 knockout mice returned to wildtype mouse levels of nicotine consumption, whereas the alpha7 knockout mice developed an emergent decrease in nicotine consumption. The alpha7 receptor knockout-induced decrease in nicotine consumption persisted for the 5-month period of the study. Both alpha7- and beta2-containing nicotinic receptors play critical roles in cognitive function and nicotine self-administration. Regarding cognitive function, beta2-containing receptors are important for maintaining normal sex differences in spatial learning and memory, whereas alpha7 receptors are important for cognitive function regardless of sex. Regarding nicotine self-administration high-affinity beta2-containing nicotinic receptors are important for consumption during the initial phase of nicotine access, but it is the alpha7 nicotinic receptors that are important for the longer-term regulation of nicotine consumption.

背景与目标： ：通常，人们一直认为，含有高亲和力烟碱受体的β2亚基是烟碱参与认知功能和尼古丁自我给药的最重要的受体亚型，而低亲和力的含α7烟碱受体尚未被认为是重要的。在当前的研究中，我们发现敲除beta2或alpha7亚基会导致小鼠的空间分辨力明显不足。两种基因敲除的损伤特征是不同的。 beta2基因敲除优先削弱男性的认知能力，而alpha7则不论性别如何均引起损害。含β2和α7的烟碱样受体对于尼古丁的自我给药也很重要，也有不同的用法。尼古丁自我管理的大多数动物模型研究都是相对短期的，而烟草成瘾的问题则是相当长期的。为了更好地模拟烟碱样受体亚型对尼古丁自我给药的长期影响，我们研究了基因敲除低亲和力α7受体与高亲和力的含β2烟碱样受体的影响。敲除这些受体及其野生型对应部分中的任一个的小鼠可在其笼子中连续5个月自由接触选择的含尼古丁和不含尼古丁的溶液。在最初的几周内，相对于野生型小鼠，含β2的烟碱样受体敲除小鼠的尼古丁消耗量显着减少，而α7敲除小鼠在接触尼古丁的初期与野生型对照无显着差异。有趣的是，在进入尼古丁的最初几周后，长期而言，β2敲除小鼠恢复了野生型小鼠的尼古丁消耗水平，而alpha7敲除小鼠出现了尼古丁消耗的突然下降。在研究的5个月中，α7受体基因敲除引起的尼古丁消耗减少一直持续。含α7和β2的烟碱样受体在认知功能和尼古丁自我给药中都起着关键作用。关于认知功能，含β2受体对于维持空间学习和记忆中的正常性别差异很重要，而alpha7受体对于无论性别如何的认知功能都很重要。关于尼古丁的自我给药，含高亲和力的含β2的尼古丁受体对于尼古丁进入初期的消耗很重要，但是α7尼古丁受体对于长期调节尼古丁的消耗很重要。

BACKGROUND & AIMS: :Metallo-β-lactamases (MBL) producing Pseudomonas aeruginosa isolates have been well characterized. Quinolones are commonly used in the treatment of carbapenem-resistant P. aeruginosa infections; however, data about PMQR in this species are scarce. The objective of this study was to report the simultaneous presence of qnrS and blaVIM-11 in P. aeruginosa, and to characterize the qnrS-harboring plasmid. Thirty-eight carbapenem-resistant P. aeruginosa isolates were recovered from a hospital in Buenos Aires during 2012. Screening for MBL was assessed by the double disk synergy test using EDTA and carbapenem discs. Plasmid DNA extraction was performed by a method using phenol-chloroform. PCR followed by sequencing was carried out to determine each MBL and PMQR allele. PCR-BseGI-RFLP was performed to detect aac-(6')-Ib-cr. The gyrA-QRDR was sequenced in those PMQR-harboring isolates. Plasmid incompatibility groups and addiction systems were characterized by PCR. The PMQR-carrying plasmid was sequenced using Illumina technology, annotated using RAST and manually curated. Eleven/38 isolates were VIM producers (blaVIM-2 and blaVIM-11) while 1/38 harbored blaIMP-13. One isolate harbored blaVIM-11 and the PMQR qnrS1; however, both markers were located in different plasmids. The qnrS1-harboring plasmid (pP6qnrS1) was 117945bp in size, presented 154 CDS and corresponded to the IncR group. In addition to qnrS1, it harbored several aminoglycoside resistance markers. Although pP6qnrS1 was non-conjugative, it presented an oriT which made it possible for this plasmid to be transferable. This is the first report on P. aeruginosa carrying both blaVIM-11 and qnrS1, plus the first detection of an IncR plasmid in Argentina.

背景与目标： 产生铜绿假单胞菌的金属β-内酰胺酶（MBL）已被很好地鉴定。喹诺酮类药物通常用于治疗对碳青霉烯耐药的铜绿假单胞菌感染。但是，有关该物种PMQR的数据很少。这项研究的目的是报告铜绿假单胞菌同时存在qnrS和blaVIM-11，并表征携带qnrS的质粒。 2012年期间，从布宜诺斯艾利斯的一家医院中回收了38株对碳青霉烯类耐药的铜绿假单胞菌分离株。通过双盘协同试验，使用EDTA和碳青霉烯圆片对MBL的筛选进行了评估。质粒DNA的提取通过使用苯酚-氯仿的方法进行。进行PCR，然后测序以确定每个MBL和PMQR等位基因。进行PCR-BseGI-RFLP以检测aac-（6'）-Ib-cr。在携带PMQR的分离物中对gyrA-QRDR进行了测序。通过PCR表征质粒不相容性组和成瘾系统。使用Illumina技术对携带PMQR的质粒进行测序，使用RAST进行注释，然后手动进行固化。 11/38个隔离株是VIM生产者（blaVIM-2和blaVIM-11），而1/38则带有blaIMP-13。一个隔离株带有blaVIM-11和PMQR qnrS1；但是，两种标记都位于不同的质粒中。携带qnrS1的质粒（pP6qnrS1）大小为117945bp，呈递154个CDS，与IncR组相对应。除qnrS1外，它还包含一些氨基糖苷抗性标记。尽管pP6qnrS1是非结合性的，但它提供了一个oriT，使得该质粒可以转移。这是关于携带blaVIM-11和qnrS1的铜绿假单胞菌的首次报道，也是阿根廷首次检测到IncR质粒的报道。

BACKGROUND & AIMS: :The fadBA operon in the fatty acid beta-oxidation pathway of P. putida KCTC1639 was blocked to induce a metabolic flux of the intermediates to the biosynthesis of medium chain-length PHA (mcl-PHA). Succinate at 150 mg l(-1) stimulated cell growth and also the biosynthesis of medium chain-length-polyhydroxyalkanoate. pH-stat fed-batch cultivation of the fadA knockout mutant P. putida KCTC1639 was carried out for 60 h, in which mcl-PHA reached 8 g l(-1) with a cell dry weight of 10.3 g l(-1).

背景与目标： ：恶臭假单胞菌KCTC1639的脂肪酸β-氧化途径中的fadBA操纵子被阻断，以诱导中间体的代谢通量，以合成中等链长的PHA（mcl-PHA）。 150 mg l（-1）的琥珀酸酯刺激细胞生长，也刺激中等链长的聚羟基链烷酸酯的生物合成。对fadA敲除突变体恶臭假单胞菌KCTC1639进行pH固定补料培养60 h，其中mcl-PHA达到8 g l（-1），细胞干重为10.3 g l（-1）。

BACKGROUND & AIMS: :Segmental duplication is a major structural variation that occurs in chromosomes. Duplication leads to the production of gene copies with increased numbers of related repeat segments, causing the global genome to be in a state of imbalance. In addition, if the added segment contains a centromeric specific DNA, the duplicated chromosome will have structural multiple centromeres. We identified a segmental duplication containing structurally tricentric regions derived from the short arm of chromosome 11 (11L∙ + 11L∙ + 11S∙11S∙11S∙11S, "∙" represents the centromeric DNA repeat loci), and analyzed its implications for cell division and genome-wide expression. In the variant, only the middle centromere of 11S∙11S∙11S∙11S is functionally active. As a result, the structurally tricentric chromosome was stable in mitosis, because it is actually a functional monocentric chromosome. However, the structurally tricentric chromosome, which usually formed a bivalent, was either arranged on the equatorial plane or was lagging, which affected its separation during meiosis. Furthermore, RNA-seq and RT-qPCR analysis showed that the segmental duplication affected genome-wide expression patterns. 34.60% of genes in repeat region showed positive dosage effect. Thus, the genes on chromosome arm 11S-2 didn't exhibit obviously dosage compensation, as illustrated by no peak around a ratio of 1.00. However, the gene dosage effect will reduce after sexual reproduction of a generation.

背景与目标： ：节段重复是发生在染色体上的主要结构变异。复制导致产生具有相关重复片段数量增加的基因拷贝，从而导致全球基因组处于失衡状态。另外，如果添加的片段包含着丝粒特异性DNA，则复制的染色体将具有多个结构着丝粒。我们鉴定出一个片段重复，该片段包含源自11号染色体短臂的结构性三中心区域（11L∙11L∙11S∙11S∙11S∙11S，“∙”代表着丝粒DNA重复基因座），并分析了其对细胞分裂和基因组的影响范围内的表达式。在变体中，只有11S∙11S∙11S∙11S的中间着丝粒起作用。结果，结构上的三中心染色体在有丝分裂中是稳定的，因为它实际上是功能性的单中心染色体。但是，通常形成二价的结构性三中心染色体要么排列在赤道平面上，要么滞后，影响了减数分裂过程中的分离。此外，RNA-seq和RT-qPCR分析表明，节段重复会影响全基因组表达模式。重复区域中34.60％的基因显示出积极的剂量效应。因此，第11S-2号染色体上的基因没有明显的剂量补偿，如1.00左右的峰没有显示。但是，一代有性繁殖后，基因剂量效应将降低。

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: :Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder for which there is no treatment. Several studies have linked the loss of MeCP2 function to alterations of brain-derived neurotrophic factor (BDNF) levels, but non-specific overexpression of BDNF only partially improves the phenotype of Mecp2-deficient mice. We and others have previously shown that huntingtin (HTT) scaffolds molecular motor complexes, transports BDNF-containing vesicles, and is under-expressed in Mecp2 knockout brains. Here, we demonstrate that promoting HTT phosphorylation at Ser421, either by a phospho-mimetic mutation or inhibition of the phosphatase calcineurin, restores endogenous BDNF axonal transport in vitro in the corticostriatal pathway, increases striatal BDNF availability and synaptic connectivity in vivo, and improves the phenotype and the survival of Mecp2 knockout mice-even though treatments were initiated only after the mice had already developed symptoms. Stimulation of endogenous cellular pathways may thus be a promising approach for the treatment of RTT patients.

背景与目标： ：X连锁的MECP2基因突变导致Rett综合征（RTT），这是一种严重的神经系统疾病，目前尚无治疗方法。几项研究已将MeCP2功能的丧失与脑源性神经营养因子（BDNF）水平的改变联系起来，但是BDNF的非特异性过表达仅部分改善了Mecp2缺陷型小鼠的表型。我们和其他人以前已经表明，亨廷顿（HTT）支架分子运动复合物，运输包含BDNF的囊泡，并在Mecp2基因敲除的大脑中表达不足。在这里，我们证明通过模仿磷酸酯酶的磷酸化突变或抑制磷酸钙调神经磷酸酶来促进Ser421处的HTT磷酸化，可在皮质口途径中体外恢复内源性BDNF轴突运输，增加纹状体BDNF的可用性和体内突触连接性，并改善表型和Mecp2基因敲除小鼠的存活-即使仅在小鼠已经出现症状后才开始治疗。因此，刺激内源性细胞途径可能是治疗RTT患者的一种有前途的方法。

BACKGROUND & AIMS: :Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consumption on cognitive performance of low-density lipoprotein receptor knockout (LDLr-/-) mice, an animal model of familial hypercholesterolemia, which display cognitive impairments since early ages. The red wine was diluted into the drinking water to a final concentration of 6% ethanol and was available for 60 days for LDLr-/- mice fed a normal or high-cholesterol diet. The results indicated that moderate red wine consumption did not alter locomotor parameters and liver toxicity. Across multiple cognitive tasks evaluating spatial learning/reference memory and recognition/identification memory, hypercholesterolemic mice drinking red wine performed significantly better than water group, regardless of diet. Additionally, immunofluorescence assays indicated a reduction of astrocyte activation and lectin stain in the hippocampus of LDLr-/- mice under consumption of red wine. These findings demonstrate that the moderate consumption of red wine attenuates short- and long-term memory decline associated with hypercholesterolemia in mice and suggest that it could be through a neurovascular action.

背景与目标： ：尽管众所周知，适量摄入红酒可以降低与高胆固醇血症相关的心血管疾病的发生率，但人们仍对其对高胆固醇血症相关认知障碍的影响存在广泛的误解。在这里，我们调查了经常喝红酒对低密度脂蛋白受体敲除（LDLr-/-）小鼠（家族性高胆固醇血症的动物模型，自幼就表现出认知功能障碍）的认知性能的推定益处。将该红酒稀释到饮用水中，使乙醇的最终浓度达到6％，并且对于喂食正常或高胆固醇饮食的LDLr-/-小鼠而言，可使用60天。结果表明，适量的红酒消费不会改变运动参数和肝毒性。在评估空间学习/参考记忆和识别/识别记忆的多个认知任务中，无论饮食如何，喝红酒的高胆固醇血症小鼠的表现均明显优于水组。另外，免疫荧光测定法表明，在喝红酒的情况下，LDLr-/-小鼠海马中的星形胶质细胞活化和凝集素染色减少。这些发现表明，适量饮用红酒可减轻小鼠高胆固醇血症相关的短期和长期记忆衰退，并表明这可能是通过神经血管作用引起的。

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: OBJECTIVE:Orthorexia is a pathological fixation about the consumption of healthy food. The present study aimed to reveal the psychometric properties of the Turkish version of ORTO-15, which was developed to evaluate orthorexia, and to investigate the relationship betweenorthorexia, and eating attitude, obsessive-compulsive symptoms, and some demographic variables. METHOD:The study included 994 participants aged between 19 and 66 years. ORTO-15, the Maudsley Obsessive-Compulsive Inventory, and the Eating Attitude Test-40 were administered to the participants. RESULTS:A 3-factor solution with varimax rotation explained 40.62% of the variance. When 4 items with factor loadings below+/- 0.50 were eliminated from ORTO-15, the Cronbach's alpha coefficient was 0.62. The remaining 11 items were thought to have statistically satisfactory properties for the Turkish version of ORTO and were collectively referred to as ORTO-11. This version was used to investigate the relationship between orthorexia, and eating attitude and obsessive-compulsive symptoms. Pathological eating attitude and obsessive-compulsive symptoms were related to orthorexia. Women exhibited more orthorexic symptoms then men. In the present study high a body mass index was an important variable for orthorexia, but only together with gender (female), pathological eating attitude, and increased obsessive-compulsive symptoms. The results, implications, and limitations of the study are discussed. CONCLUSION:ORTO-11 demonstrated statistically satisfactory properties. Orthorexia was related to pathological eating attitude and obsessive-compulsive symptoms; however, caution should be used when generalizing the reported results.

背景与目标： 目的：骨质疏松症是一种关于食用健康食品的病理学方法。本研究旨在揭示土耳其版ORTO-15的心理测量特性，该版被开发用于评估矫正症，并研究矫正症与进食态度，强迫症和某些人口统计学变量之间的关系。
方法：该研究包括994名年龄在19至66岁之间的参与者。对参与者进行ORTO-15，Maudsley强迫症量表和饮食态度测验40。
结果：3变量解的方差极大值旋转解释了40.62％的方差。当从ORTO-15中删除4个因子负载低于/-0.50的项目时，Cronbach的alpha系数为0.62。其余11项被认为具有土耳其版ORTO的统计上令人满意的性能，被统称为ORTO-11。该版本用于研究骨质疏松症与进食态度和强迫症之间的关系。病理性饮食态度和强迫症与骨质减少有关。女性比男性表现出更多的正畸症状。在本研究中，高体重指数是骨质疏松的重要变量，但仅与性别（女性），病理性饮食态度和强迫症症状增加有关。讨论了研究的结果，意义和局限性。
结论：ORTO-11具有统计学上令人满意的性能。食欲减退与病理性进食态度和强迫症有关。但是，在归纳报告结果时应格外小心。

BACKGROUND & AIMS: :A comparative mapping approach was applied in order to refine the extent and the distribution of conserved segments between human chromosome 11 (HSA11) and cattle chromosomes 15 and 29 (BTA15 and BTA29 respectively). Eight genes from HSA11 were mapped using a bovine-hamster somatic cell hybrid panel and seven represent new assignments. Adding these assignments to those present in human, mouse and cattle databases, a new conserved segment was identified between the telomeric region of HSA11 and BTA29. This brings to seven the number of conserved segments identified between HSA11 and BTA15 and 29, and our study refines their boundaries to the level of the human cytogenetic band.

背景与目标： ：为了比较人类11号染色体（HSA11）与15号和29号牛染色体（分别为BTA15和BTA29）保守区段的范围和分布，采用了比较作图法。使用牛-仓鼠体细胞杂种杂交组对来自HSA11的八个基因进行了定位，其中七个代表了新的任务。将这些分配添加到人，小鼠和牛数据库中的分配中，在HSA11和BTA29的端粒区域之间鉴定了一个新的保守区段。这使HSA11与BTA15和29之间鉴定的保守区段的数目增加到了七个，我们的研究将它们的边界改进到了人类细胞遗传学带的水平。

BACKGROUND & AIMS: :Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found in SIRT6 knockout mice, and whether a dietary intervention can rescue SIRT6 knockout mice remains unknown. In our study, we found that at the same calorie intake, a high-fat diet dramatically increased the lifespan of SIRT6 knockout mice to 26 weeks (males) and 37 weeks (females), reversed multi-organ atrophy, and reduced body weight, hypoglycemia, and premature aging. Furthermore, the high-fat diet partially but significantly normalized the global gene expression profile in SIRT6 knockout mice. Regarding the mechanism, excessive glucose uptake and glycolysis induced by the SIRT6 deficiency were attenuated in skeletal muscle through inhibition of insulin and IGF1 signaling by the high-fat diet. Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high-fatty-acid medium in vitro. Overall, the high-fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty-acid functions and supporting novel therapeutic approaches against metabolic disorders and aging-related diseases.

背景与目标： ：哺乳动物Sirtuin 6（SIRT6）参与许多基本过程的调节，尤其是代谢稳态。 SIRT6基因敲除小鼠会过早衰老，并在〜4周龄时死亡。在SIRT6基因敲除小鼠中发现了严重的糖代谢紊乱，饮食干预能否挽救SIRT6基因敲除小鼠仍是未知的。在我们的研究中，我们发现在摄入相同卡路里的情况下，高脂饮食可将SIRT6基因敲除小鼠的寿命显着延长至26周（雄性）和37周（雌性），逆转多器官萎缩并减轻体重，低血糖和过早衰老。此外，高脂饮食部分但显着地使SIRT6基因敲除小鼠的总体基因表达谱正常化。关于机制，通过高脂饮食抑制胰岛素和IGF1信号传导，减轻了SIRT6缺乏引起的过量葡萄糖摄取和糖酵解。类似地，脂肪酸而不是酮体抑制了SIRT6敲除成纤维细胞中的葡萄糖摄取，糖酵解和衰老，而PI3K的抑制作用则在体外拮抗了高脂肪酸培养基的作用。总体而言，高脂饮食可通过调节胰岛素和IGF1信号传导显着逆转SIRT6缺乏症的许多后果，为阐明SIRT6和脂肪酸功能提供了新的基础，并支持针对代谢性疾病和衰老相关疾病的新型治疗方法。