Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response

Background  

The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease) is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis.     

Chronic fluoxetine treatment in middle-aged rats induces changes in the expression of plasticity-related molecules and in neurogenesis

Background  

Antidepressants promote neuronal structural plasticity in young-adult rodents, but little is known of their effects on older animals. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) may mediate these structural changes through its anti-adhesive properties. PSA-NCAM is expressed in immature neurons and in a subpopulation of mature interneurons and its expression is modulated by antidepressants in the telencephalon of young-adult rodents.     

GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain

Background  

Neuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl^- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.     

Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices

Background  

Anesthesia is produced by a depression of central nervous system function, however, the sites and mechanisms of action underlying this depression remain poorly defined. The present study compared and contrasted effects produced by five general anesthetics on synaptic circuitry in the CA1 region of hippocampal slices.     

Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

Background  

The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated.     

Difference in icosahedral short-range order in early and late transition metal liquids

New short-range order data are presented for equilibrium and undercooled liquids of Ti and Ni. These were obtained from in situ synchrotron x-ray diffraction measurements of electrostatically levitated droplets. While the short-range order of liquid Ni is icosahedral, consistent with Frank's hypothesis, significantly distorted icosahedral order is observed in liquid Ti. This is the first experimental observation of distorted icosahedral short-range order in any liquid, although this has been predicted by theoretical studies on atomic clusters.     

Electronic structure and glass forming ability in early and late transition metal alloys

A correlation between the change in magnetic susceptibility (Δχ_exp) upon crystallisation of Cu–Zr and Hf metallic glasses (MG) with their glass forming ability (GFA) observed recently, is found to apply to Cu–Ti and Zr–Ni alloys, too. In particular, small Δχ_exp, which reflects similar electronic structures, ES, of glassy and corresponding crystalline alloys, corresponds to high GFA. Here, we studied Δχ_exp for five Cu–Ti and four Cu–Zr and Ni–Zr MGs. The fully crystalline final state of all alloys was verified from X-ray diffraction patterns. The variation of GFA with composition in Cu–Ti, Cu–Zr and Cu–Hf MGs was established from the variation of the corresponding critical casting thickness, d_c. Due to the absence of data for d_c in Ni–Zr MGs their GFA was described using empirical criteria, such as the reduced glass transition temperature. A very good correlation between Δχ_exp and d_c (and/or other criteria for GFA) was observed for all alloys studied. The correlation between the ES and GFA showed up best for Cu–Zr and NiZr₂ alloys where direct data for the change in ES (ΔES) upon crystallisation are available. The applicability of the Δχ_exp (ΔES) criterion for high GFA (which provides a simple way to select the compositions with high GFA) to other metal-metal MGs (including ternary and multicomponent bulk MGs) is briefly discussed.     

Effects of synaptic noise and filtering on the frequency response of spiking neurons

Noise can have a significant impact on the response dynamics of a nonlinear system. For neurons, the primary source of noise comes from background synaptic input activity. If this is approximated as white noise, the amplitude of the modulation of the firing rate in response to an input current oscillating at frequency omega decreases as 1/square root[omega] and lags the input by 45 degrees in phase. However, if filtering due to realistic synaptic dynamics is included, the firing rate is modulated by a finite amount even in the limit omega-->infinity and the phase lag is eliminated. Thus, through its effect on noise inputs, realistic synaptic dynamics can ensure unlagged neuronal responses to high-frequency inputs.     

Fragile X astrocytes induce developmental delays in dendrite maturation and synaptic protein expression

Background  

Fragile X syndrome is the most common inherited form of mental impairment characterized by cognitive impairment, attention deficit and autistic behaviours. The mouse model of Fragile X is used to study the underlying neurobiology associated with behavioral deficiencies. The effect of Fragile X glial cells on the development of neurons has not been studied. We used a co-culture technique in combination with morphometrics on immunostained neurons to investigate the role of astrocytes in the development delays associated with hippocampal neuron development.     

A new definition of boundary point between early reflections and late reverberation in room impulse responses

The early reflections in the room impulse response are usually defined as those observed within the initial 80 ms after the arrival of the direct sound, after which time the sound field is called reverberant. This number was chosen from measurements of other functions in a limited number of halls. In order to give an objective foundation to this time separation and to establish a physical indicator for it, a new method is proposed that defines a "transition time t(L)," which is the time at which the energy correlation between the direct plus initial sound and the subsequent decaying sound first achieves a specified low value. For various halls this number is shown and its relevance as a new parameter is discussed.     

Spontaneous dynamics and response properties of a Hodgkin-Huxley-type neuron model driven by harmonic synaptic noise

We study statistical properties, response dynamics, and information transmission in a Hodgkin-Huxley–type neuron system, modeling peripheral electroreceptors in paddlefish. In addition to sodium and potassium currents, the neuron model includes fast calcium and slow afterhyperpolarization (AHP) potassium currents. The synaptic transmission from sensory epithelium is modeled by a Poission process with a rate modulated by narrow-band noise, mimicking stochastic epithelial oscillations observed experimentally. We study how the interplay of parameters of AHP current and synaptic noise affects the statistics of spontaneous dynamics and response properties of the system. In particular, we confirm predictions made earlier with perfect integrate and fire and phase neuron models that epithelial oscillations enhance stimulus–response coherence and thus information transmission in electroreceptor system. In addition, we consider a strong stimulus regime and show that coherent epithelial oscillations may reduce variability of electroreceptor responses to time-varying stimuli.     

Sex-dependent gene expression in early brain development of chicken embryos

Background  

Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.     

Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats

Background  

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.     

早晚期混响划分对理想比值掩蔽在语音识别性能上的影响

真实环境中存在的噪声和混响会降低语音识别系统的性能。封闭空间中的混响包括直达声、早期反射和后期混响3部分,它们对语音识别系统具有不同的影响.我们研究了早期反射和后期混响的不同划分方法,以其中的早期反射为目标语音,计算出了不同的理想比值掩蔽并研究了它们对语音识别系统性能的影响;在此基础上,利用双向长短时记忆网络(BLSTM)估计理想比值掩蔽,测试它们对语音识别系统性能的影响.实验结果表明,基于Abel早期反射和后期混响的划分方法,理想比值掩蔽能够降低词错误率约2.8%;基于BLSTM的估计方法过低估计了理想比值掩蔽,未能有效提高语音识别系统的性能。     

Sodium and proton diffusion MRI as biomarkers for early therapeutic response in subcutaneous tumors

The ability to quantitate early effects of tumor therapeutic response using noninvasive imaging would have a major impact in clinical oncology. One area of active research interest is the ability to use MR techniques to detect subtle changes in tumor cellular density. In this study, sodium and proton diffusion MRI were compared for their ability to detect early cellular changes in tumors treated with a cytotoxic chemotherapy. Subcutaneous 9L gliosarcomas were treated with a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea. Both sodium and diffusion imaging modalities were able to detect changes in tumor cellularity as early as 2 days after treatment, which continued to evolve as increased signal intensities reached a maximum approximately 8 days posttreatment. Early changes in tumor sodium and apparent diffusion coefficient values were predictive of subsequent tumor shrinkage, which occurred approximately 10 days later. Overall, therapeutical induced changes in sodium and diffusion values were found to have similar dynamic and spatial changes. These findings suggest that these imaging modalities detected similar early cellular changes after treatment. The results of this study support the continued clinical testing of diffusion MRI for evaluation of early tumor treatment response and demonstrate the complementary insights of sodium MRI for oncology applications.     

Differential expression of cancer pathway-related genes in low-versus high-dose-rate-irradiated AKR/J mice

To understand the biological effects of ionizing radiation on lymphomagenesis, we reared AKR/J mice for 130 days with exposure to either high-dose-rate (HDR, 0.8 Gy/min, a single dose of 4.5 Gy) or low-dose-rate (LDR, 0.7 mGy/h, a cumulative dose of 2.1 Gy) irradiation. After 130 days, we compared the mean thymus weight, analyzed the histological changes, and measured apoptotic cell numbers using the terminal deoxynucleotidyl transferase-mediated dUTP-end labeling (TUNEL) assay. We also used microarrays and quantitative polymerase chain reaction analysis (qPCR) to analyze the expression profiles of cancer pathway-related genes in the thymuses of the mice. The mean thymus weight of the LDR-irradiated mice decreased relative to Sham- and HDR-irradiated mice. Histopathological examination revealed that the neoplastic cells in the thymuses of the Sham- and HDR-irradiated mice were pleomorphic, with marked anisocytosis and anisokaryosis, whereas the cells and their nuclei were relatively small and uniform in size in the LDR-irradiated mice. Furthermore, TUNEL assays showed that the number of apoptotic cells was higher in the LDR-irradiated mice than in the Sham- and HDR-irradiated mice. Microarray analysis showed differentially expressed genes according to carcinogenic stage (DNA repair/genomic instability, DNA damage signaling pathway, cell cycle, cancer pathway, p53 signaling pathway, apoptosis, and T- and B-cell activation). qPCR data for cancer pathway-related genes showed that Cds1 gene expression was upregulated in the LDR-irradiated mice, whereas expression of the Itga4, Myc, and Itgb1 genes was upregulated in the irradiated mice. However, the functions of cancer pathway-related genes require further study and validation.     

Identification of a set of genes showing regionally enriched expression in the mouse brain

Background

We have recorded responses from single neurons in murine visual cortex to determine the effectiveness of the input from the two murine cone photoreceptor mechanisms and whether there is any unique selectivity for cone inputs at this higher region of the visual system that would support the possibility of colour vision in mice. Each eye was stimulated by diffuse light, either 370 (strong stimulus for the ultra-violet (UV) cone opsin) or 505 nm (exclusively stimulating the middle wavelength sensitive (M) cone opsin), obtained from light emitting diodes (LEDs) in the presence of a strong adapting light that suppressed the responses of rods.

Results

Single cells responded to these diffuse stimuli in all areas of striate cortex. Two types of responsive cells were encountered. One type (135/323 – 42%) had little to no spontaneous activity and responded at either the on and/or the off phase of the light stimulus with a few impulses often of relatively large amplitude. A second type (166/323 – 51%) had spontaneous activity and responded tonically to light stimuli with impulses often of small amplitude. Most of the cells responded similarly to both spectral stimuli. A few (18/323 – 6%) responded strongly or exclusively to one or the other spectral stimulus and rarely in a spectrally opponent manner.

Conclusion

Most cells in murine striate cortex receive excitatory inputs from both UV- and M-cones. A small fraction shows either strong selectivity for one or the other cone mechanism and occasionally cone opponent responses. Cells that could underlie chromatic contrast detection are present but extremely rare in murine striate cortex.     

Anticancer activity and evaluation of apoptotic genes expression of 2-azetidinones containing anthraquinone moiety

Molecular Diversity - Nowadays, one of the principal causes of death in the world is cancer. A series of 2-azetidinones containing anthraquinone moiety with various substituents were synthesized...