分类： 生物学 >> 生物物理学 提交时间： 2016-05-15
Zhang, Shaodan
Zhang, Chun
Zhang, Shaodan
Wang, Bo
Zhu, SenHua
Xie, Yuan
Qing, Guoping
Wang, Ningli
Thomas, Ravi
Thomas, Ravi
摘要： PURPOSE. To assess the cortical structure and cerebral blood flow changes in the brain of patients with primary open-angle glaucoma (POAG). METHODS. High-resolution anatomical magnetic resonance imaging (MRI) and arterial spin labeling (ASL)-MRI were performed in 23 POAG patients and 29 controls. Patients were further divided into early-moderate and advanced groups based on mean deviation (MD) cutoff of 12 dB. A baseline scan was obtained and repeated during visual stimulation to the central preserved visual field in the more affected eye of POAG patients and a randomly selected eye of controls. Gray matter volume (GMV) and cerebral blood flow (CBF) throughout the whole brain were compared between patients and controls. RESULTS. Compared to controls, a region with significant reduction of GMV was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 503, 1698 mm3). Patients with early-moderate POAG had resting CBF similar to that of controls. However, a region with marked CBF decrease was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 1687, 13,496 mm(3)). The region with CBF reduction in advanced POAG showed good colocalization with the region with GMV decrease in this group. Following visual stimulation, patients with advanced POAG showed significantly lower increase in CBF in the occipital lobes (P < 0.001, voxels = 112, 896 mm(3)) as compared to controls (P < 0.001, voxels = 1880, 15,040 mm(3)) and early-moderate POAG (P < 0.001, voxels = 2233, 17,864 mm(3)). CONCLUSIONS. Primary open-angle glaucoma patients demonstrate a disease severity-dependent retinotopic pattern of cortical atrophy and CBF abnormalities in the visual cortex. Cerebral blood flow may be a potential biomarker for the brain involvement in glaucoma.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Qi, Renli
Qi, Renli
Li, Minghong
Ma, Yuanye
Chen, Nanhui
Li, Minghong
Ma, Yuanye
Ma, Yuanye
Chen, Nanhui
摘要： Sensory gating is a process in which the brain's response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject's behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP) can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM) sleep and Non-REM (NREM) sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Wen, Wen
Liu, Tingting
Zhang, Ting
Sun, Xinghuai
Wen, Wen
Sun, Xinghuai
Wen, Wen
Sun, Xinghuai
Zhang, Peng
He, Sheng
Gao, Jian
Sun, Xinghuai
He, Sheng
摘要： PURPOSE. This study investigated a novel motion-on-color paradigm to functionally isolate the magnocellular pathway and evaluate its diagnostic value in preperimetric glaucoma patients. METHODS. Thirty patients with preperimetric primary open-angle glaucoma and 30 controls participated in this study. They were tested in both the foveal and peripheral locations. Contrast sensitivity was assessed for the direction discrimination of a moving luminance-modulated grating presented on top of a red/green isoluminant grating. The moving test grating was designed to target the magnocellular pathway, while the background red/green isoluminant grating was designed to saturate the parvocellular pathway. The luminance-modulated grating was presented at spatial frequency of 0.5 cyc/deg, moving horizontally at four temporal frequencies (3 Hz, 8 Hz, 15 Hz, 25 Hz). Participants were asked to indicate the direction of motion for the luminance grating. As a comparison condition, frequency-doubling stimuli were also presented in the periphery and participants were asked to detect the occurrence of the frequency-doubled pattern. Two-way repeated-measures analysis of variance was performed with temporal frequency modulations as within-subject factor and group as between-subject factor, while contrast sensitivity was the dependent variable. Receiver operating characteristic (ROC) analysis was used to characterize diagnostic performance of the new procedure in comparison with the frequency-doubling tests for preperimetric glaucoma. RESULTS. The contrast sensitivity function in both the fovea and the periphery showed an inverted "V" shape with highest sensitivity in the intermediate temporal frequencies, consistent with physiological properties of the magnocellular pathway. At the fovea, compared to the control group, the sensitivity for the glaucoma patients was slightly but not significantly reduced (P > 0.05), and there was no significant interaction between groups and temporal frequency (P > 0.05). In the periphery, patients' sensitivity was significantly lower (P < 0.001) than that of normal participants, especially in high temporal frequencies, as supported by a statistically significant interaction between groups and temporal frequency (P < 0.001). The areas under ROC curves (AUROC) obtained for the motion-on-color paradigm in the periphery were 0.957 (25 Hz), 0.870 (15 Hz), 0.758 (8 Hz), and 0.561 (3 Hz) and were 0.761 for the traditional frequency-doubling test. CONCLUSIONS. The motion-on-color paradigm revealed a loss of contrast sensitivity in the peripheral visual field in preperimetric glaucoma. When applied with stimuli at high temporal frequency, the new paradigm had higher diagnostic sensitivity and specificity than the traditional frequency-doubling test. The findings also support the viewpoint that selective evaluation of magnocellular pathway function could facilitate the earlier detection of functional defects in glaucoma before visual field defects by standard perimetry.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-12
Huang, Zhaohui
Zhang, Binbin
Quan, Cao
Bian, Zehua
Hua, Dong
Huang, Zhaohui
Cheng, Haipeng
Chen, Xiaoping
Fushimi, Kazuo
Wu, Jane Y.
Wen, Pushuai
Kong, Ruirui
Chen, Mengmeng
Liu, Jianghong
Zhu, Li
Wu, Jane Y.
Zhang, Zhenfeng
Du, Xiang
摘要： Originally discovered in neuronal guidance, the Slit-Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues. Extensive promoter hypermethylation of the Slit2 gene has been observed in CRC cells, which provides a mechanistic explanation for the Slit2 downregulation in CRC. Functional studies showed that Slit2 inhibits CRC cell migration in a Robo-dependent manner. Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1. USP33 expression is downregulated in CRC samples, and reduced USP33 mRNA levels are correlated with increased tumor grade, lymph node metastasis and poor patient survival. Taken together, our data reveal USP33 as a previously unknown tumor-suppressing gene for CRC by mediating the inhibitory function of Slit-Robo signaling on CRC cell migration. Our work suggests the potential value of USP33 as an independent prognostic marker of CRC.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-11
Wu, Qiong
Xi, Sisi
Wu, Yanhong
Chang, Chi-Fu
Huang, I-Wen
Juan, Chi-Hung
Liu, Zuxiang
Wu, Yanhong
Wu, Yanhong
Fan, Jin
Fan, Jin
Fan, Jin
Fan, Jin
摘要： Information processing can be biased toward behaviorally relevant and salient stimuli by top-down (goal-directed) and bottom-up (stimulus-driven) attentional control processes respectively. However, the neural basis underlying the integration of these processes is not well understood. We employed functional magnetic resonance imaging (fMRI) and transcranial direct-current stimulation (tDCS) in humans to examine the brain mechanisms underlying the interaction between these two processes. We manipulated the cognitive load involved in top-down processing and stimulus surprise involved in bottom-up processing in a factorial design by combining a majority function task and an oddball paradigm. We found that high cognitive load and high surprise level were associated with prolonged reaction time compared to low cognitive load and low surprise level, with a synergistic interaction effect, which was accompanied by a greater deactivation of bilateral temporoparietal junction (TPJ). In addition, the TPJ displayed negative functional connectivity with right middle occipital gyrus, which is involved in bottom-up processing (modulated by the interaction effect), and the right frontal eye field (FEF), which is involved in top-down control. The enhanced negative functional connectivity between the TPJ and right FEF was accompanied by a larger behavioral interaction effect across subjects. Application of cathodal tDCS over the right TPJ eliminated the interaction effect. These results suggest that the TPJ plays a critical role in processing bottom-up information for top-down control of attention. Hum Brain Mapp 36:4317-4333, 2015. (c) 2015 Wiley Periodicals, Inc.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-11
Wu, Beibei
Wei, Yan
Wang, Yujing
Su, Tao
Liu, Ying
He, Rongqiao
He, Rongqiao
He, Rongqiao
Wu, Beibei
Wang, Yujing
Zhou, Lei
摘要： In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. A beta-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates A beta-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for agerelated cognitive impairment and diabetic encephalopathy.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
摘要： Humidity is one of the most important factors that determines the geographical distribution and survival of terrestrial animals. The ability to detect variation in humidity is conserved across many species. Here, we established a novel behavioral assay that revealed the thirsty Drosophila exhibits strong hygrotactic behavior, and it can locate water by detecting humidity gradient. In addition, exposure to high levels of moisture was sufficient to elicit proboscis extension reflex behavior in thirsty flies. Furthermore, we found that the third antennal segment was necessary for hygrotactic behavior in thirsty flies, while arista was required for the avoidance of moist air in hydrated flies. These results indicated that two types of hygroreceptor cells exist in Drosophila: one located in the third antennal segment that mediates hygrotactic behavior in thirst status, and the other located in arista which is responsible for the aversive behavior toward moist air in hydration status. Using a neural silencing screen, we demonstrated that synaptic output from the mushroom body alpha/beta surface and posterior neurons was required for both hygrotactic behavior and moisture-aversive behavior.
分类： 生物学 >> 生物物理学 >> 基因表达调控与表观遗传学 提交时间： 2016-05-11
Deng, Jianwen
Yang, Mengxue
Liu, Jianghong
Sun, Shufeng
Zhu, Li
Wu, Jane Y.
Deng, Jianwen
Yang, Mengxue
Yang, Mengxue
Chen, Yanbo
Chen, Xiaoping
Cheng, Haipeng
Li, Yang
Fushimi, Kazuo
Wu, Jane Y.
Chen, Yanbo
Xu, Qi
Chen, Yanbo
Xu, Qi
Li, Yang
摘要： FUS-proteinopathies, a group of heterogeneous disorders including ALS-FUS and FTLD-FUS, are characterized by the formation of inclusion bodies containing the nuclear protein FUS in the affected patients. However, the underlying molecular and cellular defects remain unclear. Here we provide evidence for mitochondrial localization of FUS and its induction of mitochondrial damage. Remarkably, FTLD-FUS brain samples show increased FUS expression and mitochondrial defects. Biochemical and genetic data demonstrate that FUS interacts with a mitochondrial chaperonin, HSP60, and that FUS translocation to mitochondria is, at least in part, mediated by HSP60. Down-regulating HSP60 reduces mitochondrially localized FUS and partially rescues mitochondrial defects and neurodegenerative phenotypes caused by FUS expression in transgenic flies. This is the first report of direct mitochondrial targeting by a nuclear protein associated with neurodegeneration, suggesting that mitochondrial impairment may represent a critical event in different forms of FUS-proteinopathies and a common pathological feature for both ALS-FUS and FTLD-FUS. Our study offers a potential explanation for the highly heterogeneous nature and complex genetic presentation of different forms of FUS-proteinopathies. Our data also suggest that mitochondrial damage may be a target in future development of diagnostic and therapeutic tools for FUS-proteinopathies, a group of devastating neurodegenerative diseases.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Kong, Ruirui
Wen, Pushuai
Liu, Jianghong
Zhu, Li
Wu, Jane Y.
Yi, Fengshuang
Ren, Jinqi
Feng, Wei
Yi, Fengshuang
Chen, Xiaoping
Wu, Jane Y.
Li, Xiaofei
Nie, Yongzhan
Wu, Kaichun
Fan, Daiming
Zhu, Li
Nie, Yongzhan
Wu, Kaichun
Fan, Daiming
Zhu, Li
摘要： Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated in several types of cancer, including lung cancer; however, it is not clear how SLIT functions in lung cancer. Here, our data show that SLIT inhibits cancer cell migration by activating RhoA and that myosin 9b (Myo9b) is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that specifically recognizes RhoA. We also determined that the ROBO Intracellular domain interacts with the Myo9b RhoGAP domain and inhibits its activity; therefore, SLIT-dependent activation of RhoA is mediated by ROBO inhibition of Myo9b. In a murine model, compared with control lung cancer cells, SLIT-expressing cells had a decreased capacity for tumor formation and lung metastasis. Evaluation of human lung cancer and adjacent nontumor tissues revealed that Myo9b is upregulated in the cancer tissue. Moreover, elevated Myo9b expression was associated with lung cancer progression and poor prognosis. Together, our data identify Myo9b as a key player in lung cancer and as a ROBO-interacting protein in what is, to the best of our knowledge, a newly defined SLIT/ROBO/Myo9b/RhoA signaling pathway that restricts lung cancer progression and metastasis. Additionally, our work suggests that targeting the SLIT/ROBO/Myo9b/RhoA pathway has potential as a diagnostic and therapeutic strategy for lung cancer.
分类： 生物学 >> 生物物理学 >> 神经科学 提交时间： 2016-05-11
Liu, Huilang
Bai, Fan
Ma, Yuanye
Wang, Jianhong
Liu, Huilang
Bai, Fan
Ma, Yuanye
Wang, Jianhong
Liu, Huilang
Bai, Fan
Ma, Yuanye
Wang, Jianhong
Liu, Cirong
Liu, Cirong
Liu, Cirong
Tian, Xiaoguang
Tian, Xiaoguang
Mo, Yin
Zhao, Xudong
Ma, Yuanye
摘要： Early brain development is a complex and rapid process, the disturbance of which may cause the onset of brain disorders. Based on longitudinal imaging data acquired from 6 to 16 months postnatal, we describe a systematic trajectory of monkey brain development during late infancy, and demonstrate the influence of phencyclidine (PCP) on this trajectory. Although the general developmental trajectory of the monkey brain was close to that of the human brain, the development in monkeys was faster and regionally specific. Gray matter volume began to decrease during late infancy in monkeys, much earlier than in humans in whom it occurs in adolescence. Additionally, the decrease of gray matter volume in higher-order association regions (the frontal, parietal and temporal lobes) occurred later than in regions for primary functions (the occipital lobe and cerebellum). White matter volume displayed an increasing trend in most brain regions, but not in the occipital lobe, which had a stable volume. In addition, based on diffusion tensor imaging, we found an increase in fractional anisotropy and a decrease in diffusivity, which may be associated with myelination and axonal changes in white matter tracts. Meanwhile, we tested the influence of 14-day PCP treatment on the developmental trajectories. Such treatment tended to accelerated brain maturation during late infancy, although not statistically significant. These findings provide comparative information for the understanding of primate brain maturation and neurodevelopmental disorders. (C) 2014 Elsevier Inc. All rights reserved.
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