• 1 DNA methylation and development. 复制标题 收藏 收藏

    【DNA甲基化和发育。】 复制标题 收藏 收藏
    DOI:10.1016/0167-4781(90)90076-e 复制DOI
    作者列表:Cedar H,Razin A
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【公牛睾丸促性腺激素受体,血清促性腺激素和睾丸激素浓度的产后变化以及睾丸的功能发育。】 复制标题 收藏 收藏
    DOI:10.1530/rep.1.00768 复制DOI
    作者列表:Bagu ET,Cook S,Gratton CL,Rawlings NC
    BACKGROUND & AIMS: :The primary objectives of this study were to follow the temporal patterns of testicular LH and FSH receptor (LH-R and FSH-R) concentrations and affinity (Ka) during sexual maturation in bulls and to see if such patterns could help explain the control of rapid testicular growth that occurs after 25 weeks of age, when serum gonadotropin concentrations are low. Separate groups of Hereford x Charolais calves (n = 6) were castrated every 4 weeks from 5 to 33 weeks of age and at 56 weeks of age. A week prior to castrations, from 5 to 33 weeks of age, blood was collected every 15 min for 10 h. The transition from indifferent supporting cells to Sertoli cells in seminiferous tubules was rapid between 13 and 25 weeks and rapid testis growth occurred after 25 weeks of age. Serum LH and FSH concentrations were transiently elevated at 12 weeks of age (P < 0.05). LH-R concentrations decreased from 13 to 25 weeks of age and increased to 56 weeks of age (P < 0.05). LH-RKa decreased from 9 to 17 weeks of age, increased to 29 weeks of age and declined to 33 weeks of age (P < 0.05). FSH-R concentrations declined from 17 to 25 weeks of age then increased to 56 weeks of age (P < 0.05). FSH-RKa increased from 17 to 25 weeks of age (P < 0.05). High concentrations of gonadotropins and their receptors may be critical to initiate testis growth postnatally and support it after 25 weeks of age in the face of low serum gonadotropin concentrations.
    背景与目标: : 这项研究的主要目的是跟踪公牛性成熟过程中睾丸LH和FSH受体 (lh-r和fsh-r) 浓度和亲和力 (Ka) 的时间模式,并观察这种模式是否有助于解释25周龄后睾丸快速生长的控制,当血清促性腺激素浓度较低时。从5到33周龄和56周龄,每4周对不同的Hereford x Charolais小牛 (n = 6) 进行cast割。阉割前一周,从5到33周龄,每15分钟收集一次血液,持续10小时。在13至25周之间,生精小管中从冷漠的支持细胞向Sertoli细胞的过渡迅速,并且在25周龄后睾丸迅速生长。血清LH和FSH浓度在12周龄时短暂升高 (P <0.05)。Lh-r浓度从13至25周龄降低,并增加至56周龄 (P <0.05)。Lh-rka从9周龄下降到17周龄,增加到29周龄,下降到33周龄 (P <0.05)。Fsh-r浓度从17至25周龄下降,然后增加至56周龄 (P <0.05)。Fsh-rka从17周增加到25周龄 (P <0.05)。面对低血清促性腺激素浓度,高浓度的促性腺激素及其受体对于启动出生后睾丸生长并在25周龄后支持睾丸生长可能至关重要。
  • 【神经元巨自噬: 从发育到退化。】 复制标题 收藏 收藏
    DOI:10.1016/j.mam.2006.08.009 复制DOI
    作者列表:Boland B,Nixon RA
    BACKGROUND & AIMS: :Macroautophagy, a lysosomal pathway responsible for the turnover of organelles and long-lived proteins, has been regarded mainly as an inducible process in neurons, which is mobilized in states of stress and injury. New studies show, however, that macroautophagy is also constitutively active in healthy neurons and is vital to cell survival. Neurons in the brain, unlike cells in the periphery, are protected from large-scale autophagy induction because they can use several different energy sources optimally, receive additional nutrients and neurotrophin support from glial cells, and benefit from hypothalamic regulation of peripheral nutrient supplies. Due to its exceptional efficiency, constitutive autophagy in healthy neurons proceeds in the absence of easily detectable autophagic vacuole intermediates. These intermediates can accumulate rapidly, however, when late steps in the autophagic process are blocked. Autophagic vacuoles also accumulate abnormally in affected neurons of several major neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, where they have been linked to various aspects of disease pathogenesis including neuronal cell death. The build-up of autophagic vacuoles in these neurological disorders and others may reflect either heightened autophagy induction, impairment in later digestive steps in the autophagy pathway, or both. Determining the basis for AV accumulation is critical for understanding the pathogenic significance of autophagy in a given pathologic state and for designing possible therapies based on modulating autophagy. In this review, we discuss the special features of autophagy regulation in the brain, its suspected roles in neurodevelopment and plasticity, and recent progress toward understanding how dysfunctional autophagy contributes to neurodegenerative disease.
    背景与目标: : 巨自噬是一种负责细胞器和长寿命蛋白质更新的溶酶体途径,主要被认为是神经元的诱导型过程,在应激和损伤状态下动员。然而,新的研究表明,巨自噬在健康神经元中也具有组成性活性,对细胞存活至关重要。与外围细胞不同,大脑中的神经元受到保护,免受大规模自噬诱导,因为它们可以最佳地使用几种不同的能量来源,从神经胶质细胞中获得额外的营养物质和神经营养蛋白支持,并受益于下丘脑对周围营养物质供应的调节。由于其出色的效率,健康神经元中的组成型自噬在没有易于检测的自噬液泡中间体的情况下进行。但是,当自噬过程中的后期步骤被阻止时,这些中间体可以迅速积累。自噬液泡也在几种主要神经退行性疾病 (包括阿尔茨海默氏病和帕金森氏病) 的受影响神经元中异常积累,它们与疾病发病机理的各个方面 (包括神经元细胞死亡) 有关。在这些神经系统疾病和其他疾病中,自噬液泡的积累可能反映了自噬诱导的增强,自噬途径后期消化步骤的损害,或两者兼而有之。确定AV积累的基础对于理解在给定病理状态下自噬的致病意义以及基于调节自噬设计可能的疗法至关重要。在这篇综述中,我们讨论了大脑中自噬调节的特殊特征,其在神经发育和可塑性中的可疑作用,以及了解功能失调的自噬如何导致神经退行性疾病的最新进展。
  • 【神经元活动的同步促进单个大鼠新皮层神经元在早期发育中的存活。】 复制标题 收藏 收藏
    DOI:10.1111/j.1460-9568.1997.tb01449.x 复制DOI
    作者列表:Voigt T,Baier H,Dolabela de Lima A
    BACKGROUND & AIMS: Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.

    背景与目标: 神经活动被认为在大脑皮层发育过程中起着重要作用。在这项研究中,我们研究了整体活动阻滞或增强的影响以及图案化放电对培养的大鼠新皮层神经元在体外第二周 (突触开始后) 存活的能力的影响。通过添加河豚毒素 (TTX) 和增加培养基中的镁浓度来阻断神经元活性,从而大大降低了皮质细胞的存活。通过提高外部钾浓度来增加神经元活性,显着改善了皮质神经元的存活。我们推测,在发育中的神经元网络中,神经细胞的存活受到突触介导的事件的调节,这些事件涉及细胞内钙浓度的变化。为了进一步研究这个问题,我们通过同时光学记录许多神经元的细胞内钙信号来监测发育网络的活动。这些记录表明,在低镁的新皮层神经元中,其细胞内钙浓度表达同步振荡。在培养的第二周,网络使多个细胞的细胞内钙的变化同步的能力逐渐出现,同时突触密度增加和存活神经元数量减少。通过在记录过程几天后检查已识别细胞的命运,我们发现与其他神经元共同激活的神经细胞比不参与同步事件的细胞存活的机会要高得多。这些实验表明,在早期皮质网络发育过程中,皮质神经元显示出同步的放电活动,并且神经元的存活至少部分取决于这种神经元活动模式。
  • 【T(2) 加权的显微mri和视觉系统的诱发电位在低髓转基因小鼠的发育过程中测量。】 复制标题 收藏 收藏
    DOI:10.1007/s11064-006-9121-z 复制DOI
    作者列表:Martin M,Reyes SD,Hiltner TD,Givogri MI,Tyszka JM,Fisher R,Campagnoni AT,Fraser SE,Jacobs RE,Readhead C
    BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.
    背景与目标: : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术,跟踪畸形疾病的过程,然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠,该小鼠经过工程改造以过表达golli J37,Golli-mbp基因复合物的产物,特别是在少突胶质细胞中。从21天到75天大,在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹,我们认为这是同类研究中的首次纵向研究。microMRI数据表明,在髓鞘形成峰值期间 (21-42天),明显的整体髓鞘减少,与对照组相比,JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处具有很好的相关性。In: Ransom B,Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社,伦敦,pp 555-570] 髓磷脂染色,[Campagnoni AT,macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤,在以后的年龄减弱,并且 [Lees MB,Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社,pp 197-224] VEPs,所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。总体而言,这些非侵入性技术能够在空间上解决正常发育和发育延迟的小鼠大脑中髓鞘形成的增加。
  • 【“唱歌” 的孩子: 喉科医生的视角 -- 1995。】 复制标题 收藏 收藏
    DOI:10.1016/s0892-1997(97)80066-5 复制DOI
    作者列表:Reilly JS
    BACKGROUND & AIMS: :A survey of pediatric otolaryngologists about voice disorders in children suggests that approximately 1% of children examined were noted to have voice problems, and in only one fifth of these children (0.2%) were the voice problems related to professional use of the voice, such as singing. Direct flexible laryngoscopy was the sole method of examination for 80% of the children examined by these pediatric specialists. Voice therapy for 6 months was generally recommended (88%). The survey represents an estimated clinical experience of > 160,000 children per year, and it achieved a response rate of 40% of pediatric otolaryngologists (48/120). Results suggest that the use of video and stroboscopy for examination of the pediatric voice would enhance understanding and assure correct diagnosis and treatment.
    背景与目标: : 对儿童耳鼻喉科医生进行的一项关于儿童语音障碍的调查表明,大约1% 的被检查儿童有语音问题,其中只有5分之1儿童 (0.2%) 的语音问题与专业使用语音有关,例如唱歌。直接柔性喉镜检查是由这些儿科专家检查的80% 儿童的唯一检查方法。通常建议语音治疗6个月 (88%)。该调查代表了每年> 160,000名儿童的估计临床经验,并且达到了小儿耳鼻喉科医生的40% (48/120)。结果表明,使用视频和频闪镜检查小儿语音将增强理解并确保正确的诊断和治疗。
  • 【胎儿小脑发育的磁共振成像。】 复制标题 收藏 收藏
    DOI:10.1080/14734220600589210 复制DOI
    作者列表:Triulzi F,Parazzini C,Righini A
    BACKGROUND & AIMS: :In the last few years fetal magnetic resonance imaging (MRI) has been proposed as a second level technique in the evaluation of fetal brain anomalies. It has been demonstrated that MRI is highly accurate in illustrating the morphologic changes of developing brain and fetal brain abnormalities being a useful procedure when ultrasonography is inconclusive or doubtful. Starting from the 19-20 weeks gestational age (GA), MRI can reliably depict fetal brain anatomy and locating pathology, offering a robust and reliable tool in the assessment of fetal CNS diseases. In this review both in vivo MRI quantitative and qualitative data about fetal cerebellar development are presented and compared with ultrasonography data. Fetal cerebellar development is gradual, steady, and largely comparable to the development of the supratentorial brain. Archicerebellar (flocculo-nodular lobe) and paleocerebellar (vermis) structures develop first, whereas neocerebellum (cerebellar hemispheres) develop slowly and largely after birth.
    背景与目标: : 在过去的几年中,胎儿磁共振成像 (MRI) 已被提议作为评估胎儿大脑异常的第二级技术。已经证明,当超声检查不确定或可疑时,MRI在说明发育中的大脑和胎儿大脑异常的形态变化方面非常准确,这是一种有用的方法。从19-20周的胎龄 (GA) 开始,MRI可以可靠地描述胎儿的大脑解剖结构和定位病理,为评估胎儿中枢神经系统疾病提供了可靠可靠的工具。在这篇综述中,介绍了有关胎儿小脑发育的体内MRI定量和定性数据,并将其与超声检查数据进行了比较。胎儿小脑的发育是渐进的,稳定的,并且在很大程度上与幕上大脑的发育相当。小脑 (小脑结节叶) 和古小脑 (ver) 结构首先发育,而新脑 (小脑半球) 在出生后缓慢且大部分发育。
  • 【口服多糖凝胶包衣微丸的研制1.物理机械性能。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2006.07.004 复制DOI
    作者列表:Sriamornsak P,Burton MA,Kennedy RA
    BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.
    背景与目标: : 将含有茶碱,醋酸钙和微晶纤维素的球形颗粒挤出并球形化,然后通过界面络合用六种不同的果胶或藻酸盐包被。这项研究的目的是发现涂层对物理机械性能的影响,这对于确定颗粒作为持续释放系统的效用至关重要。在核心颗粒周围形成不溶性,光滑且均匀厚的钙多糖涂层。设计了析因实验,以研究颗粒大小,多糖类型和浓度对包封效率,机械性能和其他物理特性的影响。通过扫描电子显微镜观察到包被的颗粒,根据所用的特定多糖,发现干涂层的厚度为30-80微米。颗粒的大小,多糖的类型和浓度影响包衣颗粒中茶碱的产量。尽管通过施加任何凝胶涂层可以改善颗粒的机械性能,但使用具有高含量古罗糖醛酸的藻酸盐或酰胺化的果胶涂层可提供最佳结果。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。
  • 【对象偏好对自闭症儿童任务表现和刻板印象的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0891-4222(96)00046-7 复制DOI
    作者列表:Morrison K,Rosales-Ruiz J
    BACKGROUND & AIMS: The relationship between preferred objects associated with stereotypy, stereotypic behavior, and accuracy of responding during a counting task by a child with autism was analyzed. Object preference was determined by presenting the child with different sets of objects and asking him to choose one. His choices were then rank ordered into three groupslow, medium, and high preference objects. Counting performance within each of the three object groups was then analyzed in a multi-element design, alternating preference groups. Teaching with high-preference objects occasioned more stereotypic behavior and less accurate counting than teaching with medium- and low-preference objects. Thus, there exists the possibility that teaching may be less successful with certain teaching materials, especially if those materials evoke high rates of incompatible behaviors.

    背景与目标: 分析了与自闭症儿童在计数任务中与刻板印象相关的首选对象,刻板行为和响应准确性之间的关系。对象偏好是通过向孩子展示不同的对象集并要求他选择一个来确定的。然后将他的选择排序为三个慢,中和高偏好对象。然后,在多元素设计 (交替的偏好组) 中分析了三个对象组中每个对象组的计数性能。与中低偏好对象的教学相比,高偏好对象的教学产生了更多的刻板行为和更不准确的计数。因此,存在使用某些教材进行教学可能不太成功的可能性,尤其是如果这些教材引起高度的不相容行为。
  • 【兔DQ52和DH基因在早期b细胞发育中的表达。】 复制标题 收藏 收藏
    DOI:10.1016/s0161-5890(96)00107-1 复制DOI
    作者列表:Chen HT,Alexander CB,Chen FF,Mage RG
    BACKGROUND & AIMS: Rabbits predominantly rearrange the most 3'VH gene (VH1); thus combinatorial diversity is very limited. In man and mouse, the most 3'DH gene, DQ52, is preferentially rearranged early in B-cell development. To test whether this preference for rearranging a DH gene segment based on 3' end proximity exists in rabbit, we cloned and sequenced the rabbit DQ52 gene. The 11 base pair coding region sequence is identical to a published mouse DQ52, and 81.8% similar to the human sequence. It is localized approximately 805 bp upstream of the JH1 gene. However, the 3' recombination signal sequence has an atypical nonamer. We prepared mRNA from 15- to 28-day fetal rabbits and amplified expressed VDJ sequences of mu mRNA by RT-PCR. The PCR products with VDJ rearrangements were cloned and sequenced. As expected, 44 of 45 VDJ sequences reflected use of the 3' VH1a2 gene, but the DQ52 gene was utilized very infrequently, if at all. We found only one VDJ sequence from 28-day fetal liver B-cells with 8 bp that matched the germline DQ52 sequence. Instead of expressing DQ52, another DH gene, Df was frequently expressed. We cloned the genomic Df gene and localized it about 32 kb upstream of the JH region. Thus, in contrast to man and mouse, rabbits preferentially express a DH gene located in the middle of the DH region early in B cell ontogeny. This may correlate with more frequent initial rearrangement of VH to DH in rabbit B cells.

    背景与目标: 兔子主要重排最3'VH基因 (VH1); 因此组合多样性非常有限。在人和小鼠中,最3'DH基因DQ52在b细胞发育的早期优先重排。为了测试兔子中是否存在基于3' 末端邻近度重新排列DH基因片段的偏好,我们克隆并测序了兔子DQ52基因。11个碱基对编码区序列与已发表的小鼠DQ52相同,并且81.8% 类似于人序列。它位于JH1基因上游约805 bp。但是,3' 重组信号序列具有非典型的非amer。我们从15至28天的胎兔中制备了mRNA,并通过rt-pcr扩增了mu mRNA的VDJ表达序列。克隆并测序具有VDJ重排的PCR产物。正如预期的那样,在45个VDJ序列中,有44个反映了3'vh1a2基因的使用,但是DQ52基因很少被使用 (如果有的话)。我们从28天的胎儿肝b细胞中发现只有一个VDJ序列,其8 bp与种系DQ52序列匹配。Df不表达另一个DH基因DQ52,而是经常表达。我们克隆了基因组Df基因,并将其定位在JH区域上游约32 kb。因此,与人和小鼠相比,兔子在b细胞个体发育早期优先表达位于DH区域中部的DH基因。这可能与兔b细胞中VH到DH的更频繁的初始重排有关。
  • 【功能性精子发生的发展需要早期大量的生发细胞凋亡。】 复制标题 收藏 收藏
    DOI:10.1093/emboj/16.9.2262 复制DOI
    作者列表:Rodriguez I,Ody C,Araki K,Garcia I,Vassalli P
    BACKGROUND & AIMS: Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.

    背景与目标: 在雄性生发细胞中表达高水平BclxL或Bcl2蛋白的转基因小鼠显示出高度异常的成年精子发生并伴有不育。这似乎是由于防止了睾丸中早期大量的凋亡波,而这种凋亡波在第一轮精子发生期间发生在生发细胞中。相反,在成年转基因小鼠中,不能阻止正常成年睾丸中发生的精原细胞间的零星凋亡。睾丸中的生理性早期凋亡波在时间和定位上是重合的,与促凋亡蛋白Bax的暂时高表达,该蛋白在性成熟时消失。BclxL和Bax蛋白 (Bcl2显然在正常小鼠睾丸中未表达) 的细胞内平衡 (可能受激素控制) 在这种早期凋亡波中起关键作用,这表现为在小鼠中出现类似的睾丸综合征。bax基因。凋亡波似乎是正常成熟精子发生发展所必需的,可能是因为它在某些生发细胞阶段和支持细胞之间保持了临界的细胞数比,支持细胞的正常功能和分化涉及复杂的通讯网络。
  • 【N1-Benzoyl-N2-[1-(1-萘基) 乙基]-trans-1,2-二氨基环己烷: 4-氯苯基甲酰胺 (calhex 231) 作为新的钙感应受体配体的开发,证明了有效的钙分解活性。】 复制标题 收藏 收藏
    DOI:10.1021/jm051233+ 复制DOI
    作者列表:Kessler A,Faure H,Petrel C,Rognan D,Césario M,Ruat M,Dauban P,Dodd RH
    BACKGROUND & AIMS: :A structure-activity relationship (SAR) study was performed principally at the N1 position of N1-arylsulfonyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes, a new family of calcilytics acting at the calcium sensing receptor (CaSR). The most active compound in this series was the 4-(trifluoromethoxy)benzenesulfonyl derivative 7e, which displayed an IC50 of 5.4 +/- 0.5 microM with respect to the inhibition of calcium-induced tritiated inositol phosphate ([3H]IP) accumulation in Chinese hamster ovarian (CHO) cells expressing the CaSR. Replacement of the sulfonamide linkage of this compound by a carboxamide led to a 6-fold increase in activity (7m, IC50 = 0.9 +/- 0.2 microM). Among the carboxamides synthesized, one of the most active compounds was the 4-chlorophenylcarboxamide (1S,2S,1'R)-7n (Calhex 231, IC50 = 0.33 +/- 0.02 microM). The absolute configuration of (1S,2S,1'R)-7n was deduced from an X-ray crystallographic study of one of the diastereomers of compound 7d. The stereochemical preference for the (1S,2S,1'R)-isomers can be rationalized on the basis of a three-dimensional model of the calcilytic binding pocket of the CaSR. Removal of the C-1' methyl group or replacement of the 1-naphthyl group by a 2-naphthyl or biphenyl moiety led to appreciable loss of calcilytic activity. Compounds 7e, 7m, and Calhex 231 did not stimulate [3H]IP accumulation in CHO cells expressing or not expressing the CaSR.
    背景与目标: : 主要在N1-arylsulfonyl-N2-[1-(1-萘基) 乙基]-trans-1,2-二氨基环己烷的N1位置进行了构效关系 (SAR) 研究,作用于钙感应受体 (CaSR) 的新的钙离子家族。该系列中最具活性的化合物是4-(三氟甲氧基) 苯磺酰基衍生物7e,在表达CaSR的中国仓鼠卵巢 (CHO) 细胞中,对钙诱导的tri化肌醇磷酸 ([3H]IP) 积累的抑制作用显示出5.4/- 0.5微米的IC50。用甲酰胺代替该化合物的磺酰胺键导致6倍活动增加 (7m,IC50 = 0.9 +/- 0.2微米)。在合成的甲酰胺中,最具活性的化合物之一是4-氯苯基甲酰胺 (1S,2S,1'R)-7n (Calhex 231,IC50 = 0.33 +/- 0.02微米)。(1S,2S,1'R)-7n是根据对化合物7d的非对映异构体之一的x射线晶体学研究得出的。(1S,2S,1'R)-异构体可以在CaSR的煅烧结合袋的三维模型的基础上合理化。C-1甲基的去除或2-萘基或联苯部分取代1-萘基导致煅烧活性的明显损失。化合物7e,7m,并且Calhex 231不刺激表达或不表达CaSR的CHO细胞中的 [3H]IP积累。
  • 【来自UT-7亚系UT-7/GM的红系和巨核细胞的体外发育。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Komatsu N,Kirito K,Shimizu R,Kunitama M,Yamada M,Uchida M,Takatoku M,Eguchi M,Miura Y
    BACKGROUND & AIMS: UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT-7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO-treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4 and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically mature megakaryocytic characteristics such as a developed demarcation membrane in the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a bipotential cell line that can be induced to differentiate into erythroid and megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT-7/GM cells acquired a high hemoglobin concentration by treatment with TPO, suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM cells. These results support the hypothesis that cytokines influence the programming of gene expression required for lineage commitment or differentiation.

    背景与目标: UT-7是一种人类巨核细胞白血病细胞系,其生长和存活绝对依赖于interleukin-3,粒细胞-巨噬细胞集落刺激因子 (gm-csf) 或促红细胞生成素 (EPO)。在用gm-csf长期培养UT-7后,我们分离了一个新的子系UT-7/GM。在EPO处理的UT-7/GM细胞中,血红蛋白浓度以及 γ-珠蛋白和EPO受体mRNA水平显着高于未处理的细胞。相比之下,血小板生成素 (TPO) 处理的UT-7/GM细胞中的血小板因子4和糖蛋白IIb mRNA水平远高于未处理的细胞。某些经TPO处理的细胞具有形态成熟的巨核细胞特征,例如细胞质和多小叶核中的分界膜发达。这些发现表明,UT-7/GM是一种双能细胞系,可以分别通过EPO和TPO诱导分化为红系和巨核细胞系。此外,少数UT-7/GM细胞通过用TPO处理获得高血红蛋白浓度,表明TPO部分诱导了UT-7/GM细胞的红系分化。有趣的是,gm-csf抑制EPO或TPO诱导的红细胞分化和TPO诱导的UT-7/GM细胞的巨核细胞分化。这些结果支持以下假设: 细胞因子会影响谱系承诺或分化所需的基因表达编程。
  • 【通过选择性阻断cd28预防NZB/NZW小鼠狼疮性肾炎的发展。】 复制标题 收藏 收藏
    DOI:10.1002/eji.201746923 复制DOI
    作者列表:Laurent L,Le Fur A,Bloas RL,Néel M,Mary C,Moreau A,Poirier N,Vanhove B,Fakhouri F
    BACKGROUND & AIMS: :Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4+ T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG. The effect of CD28 blockade on lupus nephritis onset, survival, production of anti-ds DNA antibodies and costimulatory molecules was evaluated. CD28 blockade prevented the development of lupus nephritis and prolonged survival during the 3-month treatment and 12 weeks after. Furthermore, the production of anti-ds DNA autoAbs was decreased. Lastly, the protective effect of CD28 blockade was associated with increased intrarenal expression of the immunoregulatory molecule, Indoleamine 2, 3-dioxygenase, of the co-inhibitory receptor programmed cell-Death - 1 (PD-1) and of its ligand programmed death ligand - 1 (PDL-1).In conclusion, CD28 blockade prevented the development of lupus nephritis in NZB/NZW F1 mice. This immunomodulatory strategy is a promising candidate for SLE therapy in humans.
    背景与目标: 系统性红斑狼疮 (SLE) 是一种慢性全身性炎症性疾病。抗狼疮标志双链DNA (ds DNA) 的自身抗体 (autoAbs) 是通过自身反应性b细胞和CD4 T细胞之间的相互作用产生和维持的。该相互作用由CD28/CD80-86/CTLA-4轴控制。在这里,我们研究了在SLE的鼠模型中,选择性阻断CD28-CD80/86共刺激相互作用是否可以缓解狼疮性肾炎的发展。为此,用anti-CD28 Fab' 片段或对照Fab'-IgG处理NZB/nzwf1小鼠3个月。评估了CD28阻断对狼疮性肾炎发作,存活,抗ds DNA抗体和共刺激分子产生的影响。CD28阻断可防止狼疮性肾炎的发展,并在3个月的治疗和12周后延长生存期。此外,抗ds DNA autoAbs的产生减少了。最后,CD28阻断的保护作用与免疫调节分子吲哚胺2,3-双加氧酶,共抑制性受体程序性细胞死亡-1 (PD-1) 及其配体程序性死亡配体-1 (PDL-1) 的肾内表达增加有关。总之,CD28阻断阻止了NZB/NZW F1小鼠狼疮性肾炎的发展。这种免疫调节策略是人类SLE治疗的有希望的候选者。
  • 【蛋氨酸腺苷转移酶2A在牛植入前发育及其相关基因组区域中的作用。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-04003-1 复制DOI
    作者列表:Ikeda S,Kawahara-Miki R,Iwata H,Sugimoto M,Kume S
    BACKGROUND & AIMS: :Methionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development.
    背景与目标: : 蛋氨酸腺苷转移酶 (MAT) 参与叶酸介导的单碳代谢,这对于植入前胚胎的短期围术期发展和围术期以后的长期表型编程都是必不可少的。在这里,我们对牛卵母细胞和植入前胚胎的免疫荧光分析揭示了在此期间MAT2A (MAT同工酶普遍表达类型的催化亚基) 的一致表达。在牛植入前胚胎的培养基中添加MAT2A抑制剂FIDAS会降低其胚泡发育,从而揭示了MAT2A在成功胚泡发育中的特殊重要性。使用染色质免疫沉淀和测序 (ChIP-seq) 探索牛囊胚中的MAT2A-associated基因组区域,确定了候选MAT2A-associated基因,不仅涉及短期内胚胎发育,而且还涉及在此期间生长,代谢和免疫功能方面的长期表型编程。这些结果表明,MAT2A在围手术期的关键参与了健康和疾病的终生规划以及成功的植入前发展。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录