日本血吸虫感染过程抗原定位的动态变化研究

本实验用ＩＦＡ方法，用日本血吸虫感染过程中的各期兔血清进行了成虫和虫卵的抗原定位研究，以观察抗原的定位随感染进程的动态变化。结果表明，用Ｒｏｓｓｍａｎ＇ｓ固定液固定的成虫石蜡切片的抗原定位及反应强弱依次为肠管壁、间质和皮层。雄性生殖系统，如睾丸可见荧光反应。雌性生殖系统未见荧光反应。雄虫的反应强度比雌虫强，尤其在间质部位最明显。成虫冰冻切片抗原定位反应最强的部位在皮层。间质较弱，肠管壁几乎阴性。对病鼠肝内虫卵抗原定位结果显示，石蜡切片抗原从感染后第４周起可见定位在虫卵内毛蚴的顶腺、侧腺及卵黄膜、卵间隙和卵壳上。顶腺和侧腺的阳性反应最强。第五周开始可见卵周有何博礼现象。冰冻切片的抗原也在第四周开始出现，定位在卵黄膜及卵壳上。     

新生大鼠耳蜗K(o)lliker器支持细胞ATP释放的机制

目的 观察体外培养的新生大鼠耳蜗K(o)lliker器支持细胞是否存在并释放ATP,初步探讨其释放机制.方法 选取出生后ld的Sprague-Dawley大鼠,分离耳蜗膜迷路,采用机械分离与酶消化相结合的方法获得单离的K(o)lliker器支持细胞.观察膜迷路和K(o)lliker器支持细胞的喹丫因染色情况.采用生物发光法,通过影响K(o)lliker器支持细胞ATP代谢、改变细胞内外Ca2浓度、抑制细胞内磷脂酶信号通路及添加缝隙连接半通道阻断剂,观察K(o)lliker器支持细胞释放ATP浓度的变化.结果 用喹丫因染色体外培养的K(o)lliker器支持细胞,发现胞质中存在大量绿色星点状染色.采用生物发光法检测的ATP标准曲线呈明显的对数线性关系.随着巴佛洛霉素A1浓度增加,K(o)lliker 器支持细胞培养液中ATP浓度逐渐降低,而随着己二酸二癸酯浓度的增加,培养液中ATP浓度逐渐升高;在一定浓度范围内,随着细胞外Ca2浓度增加,K(o)lliker器支持细胞ATP的释放减少,而随着细胞内游离Ca2浓度增加,K(o)lliker器支持细胞释放ATP量增加;培养液中加入甘珀酸钠或乌热酸抑制半通道后可以显著的降低ATP释放.此外,抑制细胞内磷脂酶信号通路也可以减少ATP的释放.结论 体外培养的新生大鼠耳蜗K(o)lliker器支持细胞存在并释放ATP,细胞内、外液中Ca2+浓度的变化可能通过调节半通道的开放而影响其ATP的释放.     

Distinct neural ensemble response statistics are associated with recognition and discrimination of natural sound textures

The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends: the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.

What makes a sound natural, and what are the neural codes that support recognition and discrimination of real-world natural sounds? Although it is known that the early auditory system decomposes sounds along fundamental acoustic dimensions such as intensity and frequency, the higher-level neural computations that mediate natural sound recognition are poorly understood. This general lack of understanding is in part attributed to the structural complexity of natural sounds, which is difficult to study with traditional auditory test stimuli, such as tones, noise, or modulated sequences. Such stimuli can reveal details of the neural representation for relatively low-level acoustic cues, yet they don’t capture the rich and diverse statistical structure of natural sounds. Thus, they cannot reveal many of the computations associated with higher-level sound properties that facilitate auditory tasks such as natural sound recognition or discrimination. A class of stationary natural sounds termed textures, such as the random sounds emanating from a running stream, a crowded restaurant, or a chorus of birds, have been proposed as alternative natural stimuli which allow for manipulating high-level acoustic structure (1). Texture sounds are composed of spatially and temporally distributed acoustic elements that are collectively perceived as a single source and are defined by their statistical features. Identification of these natural sounds has been proposed to be mediated through the integration of time-averaged summary statistics, which account for high-level structures such as the sparsity and time-frequency correlation structure found in many natural sounds (1–3). Using a generative model of the auditory system to measure summary statistics from natural texture sounds, it is possible to synthesize highly realistic synthetic auditory textures (1). This suggests that high-order statistical cues are perceptually salient and that the brain might extract these statistical features to build internal representations of sounds.Although neural activity throughout the auditory pathway is sensitive to a variety of statistical cues such as the sound contrast, modulation power spectrum, and correlation structure (4–12), how sound summary statistics contribute toward basic auditory tasks such as recognition and discrimination of sounds is poorly understood. Furthermore, it is unclear where along the auditory pathway summary statistics are represented and how they are reflected in neural activity. The inferior colliculus (IC) is one candidate midlevel structure for representing such summary statistics. As the principal midbrain auditory nucleus, the IC receives highly convergent brainstem inputs with varied sound selectivities. Neurons in the IC are selective over most of the perceptually relevant range of sound modulations and neural activity is strongly driven by multiple high-order sound statistics (4–7, 10). In previous work, we showed the correlation statistics of natural sounds are highly informative about stimulus identity and they appear to be represented in the correlation statistics of auditory midbrain neuron ensembles (4). Correlations between neurons have also been proposed as mechanisms for pitch identification (13) and sound localization (14). This broadly supports the hypotheses that high-order sound statistics are reflected in the response statistics of neural ensembles and that these neural response statistics could potentially subserve basic auditory tasks.Here using natural and synthetic texture sounds, we test the hypothesis that statistical structure in natural texture sounds modulates the response statistics of neural ensembles in the IC of unanesthetized rabbits, and that distinct neural response statistics have the potential to contribute toward sound recognition and discrimination behaviors. By comparing the performance of neural decoders with human texture perception, we find that place rate representation of sounds (neural spectrum) accumulates evidence about the sounds on relatively fast time scales (tens of milliseconds) exhibiting decoding trends that mirror those seen for human texture discrimination. High-order statistical sound cues, by comparison, are reflected in the correlation statistics of neural ensembles, which require substantially longer evidence accumulation times (>500 ms) and follow trends that mirror those measured for human texture recognition. Collectively, the findings suggest that spectrum cues and accompanying place rate representation (neural spectrum) may contribute surprisingly little toward the recognition of auditory textures. Instead, high-order statistical sound structure is reflected in the distributed patterns of correlated activity across IC neural ensembles and such neural response structure has the potential to contribute toward the recognition of natural auditory textures.     

Osteoimmunology in orthodontic tooth movement

The skeletal and immune systems share a multitude of regulatory molecules, including cytokines, receptors, signaling molecules, and signaling transducers, thereby mutually influencing each other. In recent years, several novel insights have been attained that have enhanced our current understanding of the detailed mechanisms of osteoimmunology. In orthodontic tooth movement, immune responses mediated by periodontal tissue under mechanical force induce the generation of inflammatory responses with consequent alveolar bone resorption, and many regulators are involved in this process. In this review, we take a closer look at the cellular/molecular mechanisms and signaling involved in osteoimmunology and at relevant research progress in the context of the field of orthodontic tooth movement.     

Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non–AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4⁺ T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21–treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection.     

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer’s disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.     

血液病患者信号转导及转录激活子5和叉头状转录因子3的表达

目的观察恶性血液病患者外周血中单个核细胞磷酸化STAT5及Foxp3的表达水平及其相关性。方法采用蛋白磷酸化流式细胞术分别检测45例急性白血病患者(AL)、23例慢性白血病(CL)、29例骨髓增生异常综合征(MDS)、20例重型再生障碍性贫血(SAA)及38例对照组外周血单个核细胞磷酸化STAT5(P-STAT5)及Foxp3阳性细胞的百分率。结果PSTAT5表达AL组(2.29±0.79)%、CL组(2.45±0.88)%、MDS组(2.21±0.75)%都较对照组(0.54±0.15)%增高,差异具有统计学意义(P0.05),SAA组P-STAT5表达(0.43±0.17)%较对照组降低,差异无统计学意义(P0.05);Foxp3表达AL组(3.86±1.13)%、CL组(3.60±1.10)%、MDS组(4.01±1.19)%高于对照组(0.89±0.38)%,差异具有统计学意义(P0.05),SAA组Foxp3表达(0.57±0.21)%较对照组降低,差异具有统计学意义(P0.05)。AL、CL、MDS、SAA各组P-STAT5与Foxp3表达水平都呈正相关(P0.05)。结论 STAT5及Foxp3可能共同参与了AL、CL、MDS、SAA这几类恶性血液病的发生过程,同时测定可以提供有临床意义的实验依据。