566 research outputs found

    Spinal Microglial Motility is Independent of Neuronal Activity and Plasticity in Adult Mice

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    Microglia are the resident macrophages in the central nervous system. In the spinal cord dorsal horn, microglia stay in resting condition during physiological sensory processing, and are activated under pathological conditions such as peripheral nerve injury. In cases such as this, the nearby resting microglia increase their motility and accumulate at the site of injury. However, direct evidence to support that nerve activity can enhance the motility of microglia has not yet to be reported. In this study we investigated whether the activation of spinal microglia under in vivo nerve injury may be mimicked by neuronal activity in the spinal cord slice preparation. We found that local application of spinal excitatory neurotransmitters, such as glutamate and substance P did not cause any change in the motility of microglial cells in the spinal cord dorsal horn. The motility of microglial cells is unlikely modulated by other transmitters, neuromodulators and chemokines, because similar applications such as GABA, serotonin, noradrenaline, carbachol, fractalkine or interleukin did not produce any obvious effect. Furthermore, low or high frequency stimulation of spinal dorsal root fibers at noxious intensities failed to cause any enhanced extension or retraction of the microglia processes. By contrast, focal application of ATP triggered rapid and robust activation of microglial cells in the spinal dorsal horn. Our results provide the first evidence that the activation of microglia in the spinal cord after nerve injury is unlikely due solely to neuronal activity, non-neuronal factors are likely responsible for the activation of nerve injury-related microglial cells in the spinal dorsal horn

    Characterization of intracortical synaptic connections in the mouse anterior cingulate cortex using dual patch clamp recording

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    The anterior cingulate cortex (ACC) is involved in sensory, cognitive, and executive functions. Studies of synaptic transmission and plasticity in the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions. Previous anatomic studies suggest complex local interactions among neurons within the ACC. However, there is a lack of functional studies of such synaptic connections between ACC neurons. In the present study, we characterized the neuronal connections in the superficial layers (I-III) of the mouse ACC using dual whole-cell patch clamp recording technique. Four types of synaptic connections were observed, which are from a pyramidal neuron to a pyramidal neuron, from a pyramidal neuron to an interneuron, from an interneuron to a pyramidal neuron and from an interneuron to an interneuron. These connections exist among neurons in layer II/III or between neurons located layer I and II/III, respectively. Moreover, reciprocal connections exist in all four types of paired neurons. Our results provide the first key evidence of functional excitatory and inhibitory connections in the ACC

    In vivo whole-cell patch-clamp recording of sensory synaptic responses of cingulate pyramidal neurons to noxious mechanical stimuli in adult mice

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    The anterior cingulate cortex (ACC) plays important roles in emotion, learning, memory and persistent pain. Our previous in vitro studies have demonstrated that pyramidal neurons in layer II/III of the adult mouse ACC can be characterized into three types: regular spiking (RS), intermediate (IM) and intrinsic bursting (IB) cells, according to their action potential (AP) firing patterns. However, no in vivo information is available for the intrinsic properties and sensory responses of ACC neurons of adult mice. Here, we performed in vivo whole-cell patch-clamp recordings from pyramidal neurons in adult mice ACC under urethane anesthetized conditions. First, we classified the intrinsic properties and analyzed their slow oscillations. The population ratios of RS, IM and IB cells were 10, 62 and 28%, respectively. The mean spontaneous APs frequency of IB cells was significantly greater than those of RS and IM cells, while the slow oscillations were similar among ACC neurons. Peripheral noxious pinch stimuli induced evoked spike responses in all three types of ACC neurons. Interestingly, IB cells showed significantly greater firing frequencies than RS and IM cells. In contrast, non-noxious brush did not induce any significant response. Our studies provide the first in vivo characterization of ACC neurons in adult mice, and demonstrate that ACC neurons are indeed nociceptive. These findings support the critical roles of ACC in nociception, from mice to humans

    A statistical reconstruction algorithm for positronium lifetime imaging using time-of-flight positron emission tomography

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    Positron emission tomography (PET) has been widely used for the diagnosis of serious diseases including cancer and Alzheimer's disease, based on the uptake of radiolabelled molecules that target certain pathological signatures. Recently, a novel imaging mode known as positronium lifetime imaging (PLI) has been shown possible with time-of-flight (TOF) PET as well. PLI is also of practical interest because it can provide complementary disease information reflecting conditions of the tissue microenvironment via mechanisms that are independent of tracer uptake. However, for the present practical systems that have a finite TOF resolution, the PLI reconstruction problem has yet to be fully formulated for the development of accurate reconstruction algorithms. This paper addresses this challenge by developing a statistical model for the PLI data and deriving from it a maximum-likelihood algorithm for reconstructing lifetime images alongside the uptake images. By using realistic computer simulation data, we show that the proposed algorithm can produce quantitatively accurate lifetime images.Comment: Submitted to IEEE-TPRM

    Calcium/calmodulin-dependent kinase IV contributes to translation-dependent early synaptic potentiation in the anterior cingulate cortex of adult mice

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    Calcium/calmodulin-dependent kinase IV (CaMKIV) phosphorylates the major transcription factor, cyclic AMP-responsive element binding protein (CREB), which plays key roles in synaptic plasticity and memory consolidation. Our previous study showed that long-term potentiation (LTP) in the anterior cingulate cortex (ACC) was significantly enhanced in transgenic mice overexpressing CaMKIV. Considering that the CaMKIV-CREB pathway plays a central role in the protein synthesis-dependent LTP, it is possible that upregulation of CaMKIV contributes to enhancement of LTP by promoting protein synthesis. To test this possibility, we examined the effects of transcription and translation inhibitors on synaptic potentiation induced by pairing of synaptic activity with postsynaptic depolarization (paired training) in ACC pyramidal neurons of wild-type and CaMKIV transgenic mice. We found that synaptic potentiation induced by paired training was partially inhibited by transcription or translation inhibitors both in wild-type and CaMKIV transgenic mice; the extent of inhibition was markedly larger in the CaMKIV transgenic mice than in the wild-type mice. Biochemical and immunohistochemical studies revealed that CaMKIV was distributed in the membrane, cytosol and nucleus of ACC neurons. Our results reveal in the first time a transcription- and translation-dependent component of early synaptic LTP in adult ACC synapses, and demonstrate that CaMKIV enhances early synaptic potentiation by activating new protein synthesis

    Multi-task deep learning for large-scale building detail extraction from high-resolution satellite imagery

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    Understanding urban dynamics and promoting sustainable development requires comprehensive insights about buildings. While geospatial artificial intelligence has advanced the extraction of such details from Earth observational data, existing methods often suffer from computational inefficiencies and inconsistencies when compiling unified building-related datasets for practical applications. To bridge this gap, we introduce the Multi-task Building Refiner (MT-BR), an adaptable neural network tailored for simultaneous extraction of spatial and attributional building details from high-resolution satellite imagery, exemplified by building rooftops, urban functional types, and roof architectural types. Notably, MT-BR can be fine-tuned to incorporate additional building details, extending its applicability. For large-scale applications, we devise a novel spatial sampling scheme that strategically selects limited but representative image samples. This process optimizes both the spatial distribution of samples and the urban environmental characteristics they contain, thus enhancing extraction effectiveness while curtailing data preparation expenditures. We further enhance MT-BR's predictive performance and generalization capabilities through the integration of advanced augmentation techniques. Our quantitative results highlight the efficacy of the proposed methods. Specifically, networks trained with datasets curated via our sampling method demonstrate improved predictive accuracy relative to those using alternative sampling approaches, with no alterations to network architecture. Moreover, MT-BR consistently outperforms other state-of-the-art methods in extracting building details across various metrics. The real-world practicality is also demonstrated in an application across Shanghai, generating a unified dataset that encompasses both the spatial and attributional details of buildings

    Diagnosis and molecular characterization of rabies virus from a buffalo in China: a case report

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    <p>Abstract</p> <p>Background</p> <p>Rabies virus (RABV) can infect many different species of warm-blooded animals. Glycoprotein G plays a key role in viral pathogenicity and neurotropism, and includes antigenic domains that are responsible for membrane fusion and host cell receptor recognition.</p> <p>Case presentation</p> <p>A case of buffalo rabies in China was diagnosed by direct fluorescent antibody test, G gene reverse-transcriptase polymerase chain reaction, and RABV mouse inoculation test. Molecular characterization of the RABV was performed using DNA sequencing, phylogenetic analysis and amino acid sequence comparison based on the G gene from different species of animals.</p> <p>Conclusion</p> <p>The results confirmed that the buffalo with suspected rabies was infected by RABV, which was genetically closely related to HNC (FJ602451) that was isolated from cattle in China in 2007. Comparison of the G gene among different species of animal showed that there were almost no amino acid changes among RABVs isolated from the same species of animals that distributed in a near region. However, there were many changes among RABVs that were isolated from different species of animal, or the same species from different geographic regions. This is believed to be the first case report of buffalo rabies in China, and the results may provide further information to understand the mechanism by which RABV breaks through the species barrier.</p

    SpeechX: Neural Codec Language Model as a Versatile Speech Transformer

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    Recent advancements in generative speech models based on audio-text prompts have enabled remarkable innovations like high-quality zero-shot text-to-speech. However, existing models still face limitations in handling diverse audio-text speech generation tasks involving transforming input speech and processing audio captured in adverse acoustic conditions. This paper introduces SpeechX, a versatile speech generation model capable of zero-shot TTS and various speech transformation tasks, dealing with both clean and noisy signals. SpeechX combines neural codec language modeling with multi-task learning using task-dependent prompting, enabling unified and extensible modeling and providing a consistent way for leveraging textual input in speech enhancement and transformation tasks. Experimental results show SpeechX's efficacy in various tasks, including zero-shot TTS, noise suppression, target speaker extraction, speech removal, and speech editing with or without background noise, achieving comparable or superior performance to specialized models across tasks. See https://aka.ms/speechx for demo samples.Comment: See https://aka.ms/speechx for demo sample

    Effective suppression of parametric instabilities with decoupled broadband lasers in plasma

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    A theoretical analysis for the stimulated Raman scattering (SRS) instability driven by two laser beams with certain frequency difference is presented. It is found that strong coupling and enhanced SRS take place only when the unstable regions for each beam are overlapped in the wavenumber space. Hence a threshold of the beam frequency difference for their decoupling is found as a function of their intensity and plasma density. Based upon this, a strategy to suppress the SRS instability with decoupled broadband lasers (DBLs) is proposed. A DBL can be composed of tens or even hundreds of beamlets, where the beamlets are distributed uniformly in a broad spectrum range such as over 10% of the central frequency. Decoupling among the beamlets is found due to the limited beamlet energy and suitable frequency difference between neighboring beamlets. Particle-in-cell simulations demonstrate that SRS can be almost completely suppressed with DBLs under the laser intensity ∼ 1015 W/cm2. Moreover, stimulated Brillouin scattering (SBS) will be suppressed simultaneously with DBLs can be attractive for driving inertial confined fusion
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