分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-18
Chen, Juan
He, Yingchen
Zhu, Ziyun
Peng, Yujia
Zhang, Xilin
Fang, Fang
Chen, Juan
He, Yingchen
Zhu, Ziyun
Peng, Yujia
Zhang, Xilin
Fang, Fang
Fang, Fang
Fang, Fang
Zhou, Tiangang
摘要：Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-15
摘要：A widely appreciated aspect of developmental robustness is pattern formation in proportion to size. But how such scaling features emerge dynamically remains poorly understood. Here we generate a data set of the expression profiles of six gap genes in Drosophila melanogaster embryos that differ significantly in size. Expression patterns exhibit size-dependent dynamics both spatially and temporally. We uncover a dynamic emergence of under-scaling in the posterior, accompanied by reduced expression levels of gap genes near the middle of large embryos. Simulation results show that a size-dependent Bicoid gradient input can lead to reduced Kruppel expression that can have long-range and dynamic effects on gap gene expression in the posterior. Thus, for emergence of scaled patterns, the entire embryo may be viewed as a single unified dynamic system where maternally derived size-dependent information interpreted locally can be propagated in space and time as governed by the dynamics of a gene regulatory network.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要：What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要：Vesicle recycling is pivotal for maintaining reliable synaptic signaling, but its basic properties remain poorly understood. Here, we developed an approach to quantitatively analyze the kinetics of vesicle recycling with exquisite signal and temporal resolution at the calyx of Held synapse. The combination of this electrophysiological approach with electron microscopy revealed that similar to 80% of vesicles (similar to 270,000 out of similar to 330,000) in the nerve terminal are involved in recycling. Under sustained stimulation, recycled vesicles start to be reused in tens of seconds when similar to 47% of the preserved vesicles in the recycling pool (RP) are depleted. The heterogeneity of vesicle recycling as well as two kinetic components of RP depletion revealed the existence of a replenishable pool of vesicles before the priming stage and led to a realistic kinetic model that assesses the size of the subpools of the RP. Thus, our study quantified the kinetics of vesicle recycling and kinetically dissected the whole vesicle pool in the calyceal terminal into the readily releasable pool (similar to 0.6%), the readily priming pool (similar to 46%), the premature pool (similar to 33%), and the resting pool (similar to 20%).
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
Wei, Yan
Han, Chanshuai
Wang, Yujing
Wu, Beibei
Su, Tao
Liu, Ying
He, Rongqiao
Wang, Yujing
Wu, Beibei
Liu, Ying
He, Rongqiao
摘要：Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Song, Qinghe
Mao, Beibei
Cheng, Jinbo
Gao, Yuhao
Yuan, Zengqiang
Song, Qinghe
Gao, Yuhao
Yuan, Zengqiang
Jiang, Ke
Meng, Songshu
Chen, Jun
摘要：The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor suppressor pathway, functions as an oncoprotein in a variety of cancers. However, its contribution to breast cancer remains controversial. This study investigated the role of YAP in breast cancer cells under nutrient deprivation (ND). Here, we show that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. Furthermore, in response to ND, YAP increased the autolysosome degradation, thereby enhancing the cellular autophagic flux in breast cancer cells. Of note, autophagy is crucial for YAP to protect MCF7 cells from apoptosis under ND conditions. In addition, the TEA domain (TEAD) family of growth-promoting transcription factors was indispensable for YAP-mediated regulation of autophagy. Collectively, our data reveal a role for YAP in promoting breast cancer cell survival upon ND stress and uncover an unappreciated function of YAP/TEAD in the regulation of autophagy.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-12
摘要：The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The beneficial effects of clozapine on behavioral impairment might be a specific indicator of schizophrenia-related cognitive impairment.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要：The neural correlates of associative memory in healthy older adults were investigated by examining the correlation of associative memory performance with spontaneous brain oscillations. Eighty healthy older adults underwent a resting-state functional MRI and took a paired-associative learning test (PALT). Correlations between the amplitude of low-frequency fluctuations (ALFF) as well as fractional ALFF (fALFF) in the whole brain and PALT scores were calculated. We found that spontaneous activity as indexed by both ALFF and fALFF in the parahippocampal gyrus (PHG) was significantly positively correlated with associative memory performance, suggesting that the PHG plays a critical role in associative memory in older people.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-12
摘要：The human LGN and SC consist of distinct layers, but their layer-specific response properties remain poorly understood. In this fMRI study, we characterized visual response properties of the magnocellular (M) and parvocellular (P) layers of the human LGN, as well as at different depths in the SC. Results show that fMRI is capable of resolving layer-specific signals from the LGN and SC. Compared to the P layers of the LGN, the M layers preferred higher temporal frequency, lower spatial frequency stimuli, and their responses saturated at lower contrast. Furthermore, the M layers are colorblind while the P layers showed robust response to both chromatic and achromatic stimuli. Visual responses in the SC were strongest in the superficial voxels, which showed similar spatiotemporal and contrast response properties as the M layers of the LGN, but were sensitive to color and responded strongly to isoluminant color stimulus. Thus, the non-invasive fMRI measures show that the M and P layers of human LGN have similar response properties as that observed in non-human primates and the superficial layers of the human SC prefer transient inputs but are not colorblind. (C) 2015 Elsevier Inc. All rights reserved.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
摘要：The Hippo signaling pathway restricts organ size by inactivating the Yorkie (Yki)/Yes-associated protein (YAP) family proteins. The oncogenic Yki/YAP transcriptional coactivator family promotes tissue growth by activating target gene transcription, but the regulation of Yki/YAP activation remains elusive. In mammalian cells, we identified Brg1, a major subunit of chromatin-remodeling SWI/SNF family proteins, which interacts with YAP. This finding led us to investigate the in vivo functional interaction of Yki and Brahma (Brm), the Drosophila homolog of Brg1. We found that Brm functions at the downstream of Hippo pathway and interacts with Yki and Scalloped (Sd) to promotes Yki-dependent transcription and tissue growth. Furthermore, we demonstrated that Brm is required for the Crumbs (Crb) dysregulation-induced Yki activation. Interestingly, we also found that crb is a downstream target of Yki-Brm complex. Brm physically binds to the promoter of crb and regulates its transcription through Yki. Together, we showed that Brm functions as a critical regulator of Hippo signaling during tissue growth and plays an important role in the feedback loop between Crb and Yki. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
分类： 生物学 >> 生物物理学 >> 细胞生物学 提交时间： 2016-05-12
Yu, Zhouliang
Zhou, Xiang
Wang, Wenjing
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Wang, Zichen
Cui, Lei
Shen, Jing
Ou, Guangshuo
Yang, Na
Chen, Ping
Xu, Rui-Ming
Li, Guohong
Yu, Zhouliang
Deng, Wenqiang
Fang, Junnan
Hu, Hao
Peng, Shengyi
Li, Shangze
摘要：The H3 histone variant CENP-A is an epigenetic marker critical for the centromere identity and function. However, the precise regulation of the spatiotemporal deposition and propagation of CENP-A at centromeres during the cell cycle is still poorly understood. Here, we show that CENP-A is phosphorylated at Ser68 during early mitosis by Cdk1. Our results demonstrate that phosphorylation of Ser68 eliminates the binding of CENP-A to the assembly factor HJURP, thus preventing the premature loading of CENP-A to the centromere prior to mitotic exit. Because Cdk1 activity is at its minimum at the mitotic exit, the ratio of Cdk1/PP1 alpha activity changes in favor of Ser68 dephosphorylation, thus making CENP-A available for centromeric deposition by HJURP. Thus, we reveal that dynamic phosphorylation of CENP-A Ser68 orchestrates the spatiotemporal assembly of newly synthesized CENP-A at active centromeres during the cell cycle.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Shang, Congping
Liu, Zhihui
Chen, Zijun
Shi, Yingchao
Wang, Qian
Liu, Su
Li, Dapeng
Cao, Peng
Shang, Congping
Chen, Zijun
Shi, Yingchao
摘要：The fear responses to environmental threats play a fundamental role in survival. Little is known about the neural circuits specifically processing threat-relevant sensory information in the mammalian brain. We identified parvalbumin-positive (PV+) excitatory projection neurons in mouse superior colliculus (SC) as a key neuronal subtype for detecting looming objects and triggering fear responses. These neurons, distributed predominantly in the superficial SC, divergently projected to different brain areas, including the parabigeminal nucleus (PBGN), an intermediate station leading to the amygdala. Activation of the PV+ SC-PBGN pathway triggered fear responses, induced conditioned aversion, and caused depression-related behaviors. Approximately 20% of mice subjected to the fear-conditioning paradigm developed a generalized fear memory.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-12
摘要：The brain constantly creates perceptual predictions about forthcoming stimuli to guide perception efficiently. Abundant studies have demonstrated that perceptual predictions modulate sensory activities depending on whether the actual inputs are consistent with one particular prediction. In real-life contexts, however, multiple and even conflicting predictions might concurrently exist to be tested, requiring a multiprediction coordination process. It remains largely unknown how multiple hypotheses are conveyed and harmonized to guide moment-by-moment perception. Based on recent findings revealing that multiple locations are sampled alternatively in various phase of attentional rhythms, we hypothesize that this oscillation-based temporal organization mechanism may also underlie the multiprediction coordination process. To address the issue, we used well established priming paradigms in combination with a time-resolved behavioral approach to investigate the fine temporal dynamics of the multiprediction harmonization course in human subjects. We first replicate classical priming effects in slowly developing trends of priming time courses. Second, after removing the typical priming patterns, we reveal a new theta-band (similar to 4 Hz) oscillatory component in the priming behavioral data regardless of whether the prime was masked. Third, we show that these theta-band priming oscillations triggered by congruent and incongruent primes are in an out-of-phase relationship. These findings suggest that perceptual predictions return to low-sensory areas not continuously but recurrently in a theta-band rhythm (every 200-300 ms) and that multiple predictions are dynamically coordinated in time by being conveyed in different phases of the theta-band oscillations to achieve dissociated but temporally organized neural representations.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-12
摘要：Tandem-arranged PDZ [PSD-95 (postsynaptic density-95), Dlg (discs large homologue) and ZO-1 (zonula occludens-1)] domains often form structural and functional supramodules with distinct target-binding properties. In the present study, we found that the two PDZ domains within the PDZ34 tandem of Scribble, a cell polarity regulator, tightly pack in a 'front-to-back' mode to form a compact supramodule. Although PDZ4 contains a distorted alpha B/beta B pocket, the attachment of PDZ4 to PDZ3 generates an unexpected interdomain pocket that is adjacent to and integrates with the canonical aB/aB pocket of PDZ3 to form an expanded target-binding groove. The structure of the PDZ34-target peptide complex further demonstrated that the peptide binds to this expanded target-binding groove with its upstream residues anchoring into the interdomain pocket directly. Mutations of the interdomain pocket and disruptions of the PDZ34 supramodule both interfere with its target-binding capacity. Therefore, the interdomain interface between the PDZ34 supramodule is intrinsically required for its target recognition and determines its target-binding specificity. This interdomain interface-mediated specific recognition may represent a novel mode of target recognition and would broaden the target-binding versatility for PDZ supramodules. The supramodular nature and target recognitionmode of the PDZ34 tandem found in the present study would also help to identify the new binding partners of Scribble and thus may direct further research on the PDZ domain-mediated assembly of Scribble polarity complexes.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Rao, Jia-Sheng
Zhao, Can
Liu, Zuxiang
Yang, Zhao-Yang
Li, Xiao-Guang
Ma, Manxiu
Liu, Zuxiang
Yang, Zhao-Yang
Li, Xiao-Guang
摘要：Purpose: To investigate the longitudinal brain regional homogeneity (ReHo) changes in nonhuman primate after spinal cord injury (SCI) by resting-state functional magnetic resonance imaging (fMRI). Methods: Three adult female rhesus monkeys underwent unilateral thoracic cord injury. A resting-state fMRI examination was performed in the healthy stage and 4, 8, and 12 weeks after the injury. The ReHo value of each voxel in the monkey brain was calculated and compared between pre- and post-SCI monkeys with paired t test. The regions of interest (ROIs) in the significantly changed ReHo regions were set. The correlations between the ReHo change and the time after injury were also determined. Results: Compared with those in healthy period, the ReHo values of the left premotor cortex and the anterior cingulate cortex (ACC) in post-SCI rhesus monkeys significantly increased in 4-week follow-up examinations. The ReHo values of posterior cingulate cortex, left precuneus, left temporal parietooccipital area, and bilateral superior parietal lobules decreased at 8-week follow-up examinations. In 12-week follow-up examinations, the ReHo values of the left postcentral gyrus, right caudate nucleus, and superior temporal gyrus increased. Correlation analysis showed positive correlations between left ACC and the postoperative time. Conclusion: SCI can change the regional synchronism of brain activity in sensorimotor system and the default mode network. These findings may help us to understand the potential pathophysiological changes in the central nervous system after SCI. (C) 2015 Elsevier Inc. All rights reserved.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-12
Guo, Chao
Du, Yifei
Yuan, Deliang
Li, Meixia
Gong, Haiyun
Gong, Zhefeng
Liu, Li
Guo, Chao
Du, Yifei
Yuan, Deliang
Liu, Li
摘要：Orientation, the spatial organization of animal behavior, is an essential faculty of animals. Bacteria and lower animals such as insects exhibit taxis, innate orientation behavior, directly toward or away from a directional cue. Organisms can also orient themselves at a specific angle relative to the cues. In this study, using Drosophila as a model system, we established a visual orientation conditioning paradigm based on a flight simulator in which a stationary flying fly could control the rotation of a visual object. By coupling aversive heat shocks to a fly's orientation toward one side of the visual object, we found that the fly could be conditioned to orientate toward the left or right side of the frontal visual object and retain this conditioned visual orientation. The lower and upper visual fields have different roles in conditioned visual orientation. Transfer experiments showed that conditioned visual orientation could generalize between visual targets of different sizes, compactness, or vertical positions, but not of contour orientation. Rut-Type I adenylyl cyclase and Dnc-phosphodiesterase were dispensable for visual orientation conditioning. Normal activity and scb signaling in R3/R4d neurons of the ellipsoid body were required for visual orientation conditioning. Our studies established a visual orientation conditioning paradigm and examined the behavioral properties and neural circuitry of visual orientation, an important component of the insect's spatial navigation.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
He, Jing
Wei, JingKuan
Rizak, Joshua D.
Wang, JianHong
Hu, XinTian
Ma, YuanYe
Wei, JingKuan
Rizak, Joshua D.
Chen, YanMei
Hu, XinTian
Ma, YuanYe
Hu, XinTian
Ma, YuanYe
摘要：Odor detection applications are needed by human societies in various circumstances. Rodent offers unique advantages in developing biologic odor detection systems. This report outlines a novel apparatus designed to train maximum 5 mice automatically to detect odors using a new olfactory, relative go no-go, operant conditioning paradigm. The new paradigm offers the chance to measure real-time reliability of individual animal's detection behavior with changing responses. All of 15 water-deprivation mice were able to learn to respond to unpredictable delivering of the target odor with higher touch frequencies via a touch sensor. The mice were continually trained with decreasing concentrations of the target odor (n-butanol), the average correct percent significantly dropped when training at 0.01% solution concentration; the alarm algorithm showed excellent recognition of odor detection behavior of qualified mice group through training. Then, the alarm algorithm was repeatedly tested against simulated scenario for 4 blocks. The mice acted comparable to the training period during the tests, and provided total of 58 warnings for the target odor out of 59 random deliveries and 0 false alarm. The results suggest this odor detection method is promising for further development in respect to various types of odor detection applications.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Wang, Ying
Yang, Lizhuang
Gu, Feng
Li, Xiaoming
Zha, Rujing
Wei, Zhengde
Pei, Yakun
Zhou, Yifeng
Zhang, Xiaochu
Wang, Ying
Yang, Lizhuang
Gu, Feng
Li, Xiaoming
Zha, Rujing
Wei, Zhengde
Pei, Yakun
Zhou, Yifeng
Zhang, Xiaochu
Liu, Ying
Li, Xiaoming
摘要：Novelty seeking (NS) is a personality trait reflecting excitement in response to novel stimuli. High NS is usually a predictor of risky behaviour such as drug abuse. However, the relationships between NS and risk-related cognitive processes, including individual risk preference and the brain activation associated with risk prediction, remain elusive. In this fMRI study, participants completed the Tridimensional Personality Questionnaire to measure NS and performed a probabilistic decision making task. Using a mathematical model, we estimated individual risk preference. Brain regions associated with risk prediction were determined via fMRI. The NS score showed a positive correlation with risk preference and a negative correlation with the activation elicited by risk prediction in the right posterior insula (r-PI), left anterior insula (l-AI), right striatum (r-striatum) and supplementary motor area (SMA). Within these brain regions, only the activation associated with risk prediction in the r-PI showed a correlation with NS after controlling for the effect of risk preference. Resting-state functional connectivity between the r-PI and r-striatum/l-AI was negatively correlated with NS. Our results suggest that high NS may be associated with less aversion to risk and that the r-PI plays an important role in relating risk prediction to NS.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
摘要：Normal aging is associated with greater decline in associative memory relative to item memory due to impaired recollection. Familiarity may also contribute to associative recognition when stimuli are perceived as a 'unitized' representation. Given that familiarity is relatively preserved in older adults, we explored whether age-related associative memory deficits could be attenuated when associations were unitized (i.e., compounds) compared with those non-unitized (i.e., unrelated word pairs). Young and older adults performed an associative recognition task while electroencephalogram (EEG) was recorded. Behavioral results showed that age differences were smaller for recognition of compounds than for unrelated word pairs. ERP results indicated that only compounds evoked an early frontal old/new effect in older adults. Moreover, the early frontal old/new effect was positively correlated with associative discrimination accuracy. These findings suggest that reduced age-related associative deficits under unitized condition may be associated with the presence of familiarity-based retrieval of compounds in older adults. (C) 2015 Elsevier Inc. All rights reserved.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-12
Chen, Nihong
Li, Sheng
Fang, Fang
Chen, Nihong
Li, Sheng
Fang, Fang
Chen, Nihong
Li, Sheng
Fang, Fang
Chen, Nihong
Fang, Fang
Bi, Taiyong
Bi, Taiyong
Zhou, Tiangang
Liu, Zili
摘要：Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decisionmaking area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. (C) 2015 Elsevier Inc. All rights reserved.
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