Neuron segmentation using 3D wavelet integrated encoder-decoder network.

MOTIVATION: 3D neuron segmentation is a key step for the neuron digital reconstruction, which is essential for exploring brain circuits and understanding brain functions. However, the fine line-shaped nerve fibers of neuron could spread in a large region, which brings great computational cost to the neuron segmentation. Meanwhile, the strong noises and disconnected nerve fibers bring great challenges to the task. RESULTS: In this article, we propose a 3D wavelet and deep learning-based 3D neuron segmentation method. The neuronal image is first partitioned into neuronal cubes to simplify the segmentation task. Then, we design 3D WaveUNet, the first 3D wavelet integrated encoder-decoder network, to segment the nerve fibers in the cubes; the wavelets could assist the deep networks in suppressing data noises and connecting the broken fibers. We also produce a Neuronal Cube Dataset (NeuCuDa) using the biggest available annotated neuronal image dataset, BigNeuron, to train 3D WaveUNet. Finally, the nerve fibers segmented in cubes are assembled to generate the complete neuron, which is digitally reconstructed using an available automatic tracing algorithm. The experimental results show that our neuron segmentation method could completely extract the target neuron in noisy neuronal images. The integrated 3D wavelets can efficiently improve the performance of 3D neuron segmentation and reconstruction. AVAILABILITYAND IMPLEMENTATION: The data and codes for this work are available at https://github.com/LiQiufu/3D-WaveUNet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A self-supervised feature-standardization-block for cross-domain lung disease classification.

With the advance of deep learning technology, convolutional neural network (CNN) has been wildly used and achieved the state-of-the-art performances in the area of medical image classification. However, most existing medical image classification methods conduct their experiments on only one public dataset. When applying a well-trained model to a different dataset selected from different sources, the model usually shows large performance degradation and needs to be fine-tuned before it can be applied to the new dataset. The goal of this work is trying to solve the cross-domain image classification problem without using data from target domain. In this work, we designed a self-supervised plug-and-play feature-standardization-block (FSB) which consisting of image normalization (INB), contrast enhancement (CEB) and boundary detection blocks (BDB), to extract cross-domain robust feature maps for deep learning framework, and applied the network for chest x-ray-based lung diseases classification. Three classic deep networks, i.e. VGG, Xception and DenseNet and four chest x-ray lung diseases datasets were employed for evaluating the performance. The experimental result showed that when employing feature-standardization-block, all three networks showed better domain adaption performance. The image normalization, contrast enhancement and boundary detection blocks achieved in average 2%, 2% and 5% accuracy improvement, respectively. By combining all three blocks, feature-standardization-block achieved in average 6% accuracy improvement.

Clinical Value of Platelet Indices in Premature Coronary Artery Disease.

Platelets play an important role in the pathophysiology of coronary artery disease. However, the clinical value of platelet indices in premature coronary heart disease remains largely unknown.Consecutive patients referred for coronary angiography were evaluated (n = 1675). Patients were stratified into premature coronary heart disease (n = 679, age < 55 for male and age < 65 for female), late-onset coronary heart disease (n = 772, age ≥ 55 for male and age ≥ 65 for female), and control (n = 224, age < 55 for male and age < 65 for female). Their clinical and laboratory parameters were collected. The relationship between platelet indices and premature coronary artery disease was analyzed.In univariate analysis, platelet indices showed no significant association with the presence of premature coronary heart disease (P > 0.05). After adjustment for traditional risk factors, mean platelet volume (0.823 [0.683-0.993], P = 0.042) and platelet-large cell ratio (0.976 [0.954-0.999], P = 0.040) were negatively correlated with the presence of premature coronary heart disease. The platelet-to-lymphocyte ratio was statistically significant among different numbers of coronary lesions (P = 0.035). In subgroup analysis, platelet-large cell ratio (1.190 [1.010-1.403], P = 0.038) was an independent risk factor of coronary restenosis after percutaneous coronary intervention.Platelet indices were associated with the prevalence, severity, and coronary restenosis after percutaneous coronary intervention suggesting their possible clinical application in premature coronary heart disease.

TASK1 and TASK3 in orexin neuron of lateral hypothalamus contribute to respiratory chemoreflex by projecting to nucleus tractus solitarius.

TWIK-related acid-sensitive potassium channels (TASKs)-like current was recorded in orexin neurons in the lateral hypothalamus (LH), which are essential in respiratory chemoreflex. However, the specific mechanism responsible for the pH-sensitivity remains elusive. Thus, we hypothesized that TASKs contribute to respiratory chemoreflex. In the present study, we found that TASK1 and TASK3 were expressed in orexin neurons. Blocking TASKs or microinjecting acid artificial cerebrospinal fluid (ACSF) in the LH stimulated breathing. In contrast, alkaline ACSF inhibited breathing, which was attenuated by blocking TASK1. Damage of orexin neurons attenuated the stimulatory effect on respiration caused by microinjection of acid ACSF (at a pH of 6.5) or TASKs antagonists. The orexinA-positive fiber and orexin type 1 receptor (OX1R) neurons were located in the nucleus tractus solitarius (NTS). The exciting effect of acidosis in the LH on respiration was inhibited by blocking OX1R of the NTS. Taken together, we conclude that orexin neurons sense the extracellular pH change through TASKs and regulate respiration by projecting to the NTS.

Employing Visible-Light Photoredox Catalysis in Multicomponent-Multicatalyst Reactions: One-Pot Synthesis of Spiroquinazolin-2-(thi)ones.

The multicomponent-multicatalyst reaction ((MC)2R) and visible-light catalysis have emerged as green and powerful strategies for achieving ideal syntheses. Here, we report the first example of a visible-light-induced approach toward spiroquinazolin(thi)ones. This (MC)2R features an eco-friendly energy source and solvent, metal-free catalysts, step- and atom-economy, a relay catalysis strategy, air as green oxidant, mild conditions, and easily accessible starting materials.

Reassessment of the Effect of Transcutaneous Auricular Vagus Nerve Stimulation Using a Novel Burst Paradigm on Cardiac Autonomic Function in Healthy Young Adults.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS: Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 µsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS: Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION: The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

The projections from the anterior cingulate cortex to the nucleus accumbens and ventral tegmental area contribute to neuropathic pain-evoked aversion in rats.

Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10-14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.

MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation.

MMP13 (matrix metallopeptidase 13) plays a key role in bone metabolism and cancer development, but has no known functions in Alzheimer's disease. In this study, we used high-throughput small molecule screening in SH-SY5Y cells that stably expressed a luciferase reporter gene driven by the BACE1 (ß-site amyloid precursor protein cleaving enzyme 1) promoter, which included a portion of the 5' untranslated region (5'UTR). We identified that CL82198, a selective inhibitor of MMP13, decreased BACE1 protein levels in cultured neuronal cells. This effect was dependent on PI3K (phosphatidylinositide 3-kinase) signalling, and was unrelated to BACE1 gene transcription and protein degradation. Further, we found that eukaryotic translation initiation factor 4B (eIF4B) played a key role, as the mutation of eIF4B at serine 422 (S422R) or deletion of the BACE1 5'UTR attenuated MMP13-mediated BACE1 regulation. In APPswe/PS1E9 mice, an animal model of Alzheimer's disease, hippocampal Mmp13 knockdown or intraperitoneal CL82198 administration reduced BACE1 protein levels and the related amyloid-ß precursor protein processing, amyloid-ß load and eIF4B phosphorylation, whereas spatial and associative learning and memory performances were improved. Collectively, MMP13 inhibition/CL82198 treatment exhibited therapeutic potential for Alzheimer's disease, via the translational regulation of BACE1.

Reverse active learning based atrous DenseNet for pathological image classification.

BACKGROUND: Due to the recent advances in deep learning, this model attracted researchers who have applied it to medical image analysis. However, pathological image analysis based on deep learning networks faces a number of challenges, such as the high resolution (gigapixel) of pathological images and the lack of annotation capabilities. To address these challenges, we propose a training strategy called deep-reverse active learning (DRAL) and atrous DenseNet (ADN) for pathological image classification. The proposed DRAL can improve the classification accuracy of widely used deep learning networks such as VGG-16 and ResNet by removing mislabeled patches in the training set. As the size of a cancer area varies widely in pathological images, the proposed ADN integrates the atrous convolutions with the dense block for multiscale feature extraction. RESULTS: The proposed DRAL and ADN are evaluated using the following three pathological datasets: BACH, CCG, and UCSB. The experiment results demonstrate the excellent performance of the proposed DRAL + ADN framework, achieving patch-level average classification accuracies (ACA) of 94.10%, 92.05% and 97.63% on the BACH, CCG, and UCSB validation sets, respectively. CONCLUSIONS: The DRAL + ADN framework is a potential candidate for boosting the performance of deep learning models for partially mislabeled training datasets.

Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis.

Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.5 within 10 minutes initiation of ischaemia. Acid-sensing ion channels (ASICs) can be activated by pH drops from 7.4 to 7.0 or lower and permeates to Ca2+ entrance. Thus, activation of ASIC1a can mediate the intracellular Ca2+ accumulation and play crucial roles in apoptosis of cells. However, the role of ASICs in renal ischaemic injury is unclear. The aim of the present study was to test the hypothesis that ischaemia increases renal epithelia cell apoptosis through ASIC1a-mediated calcium entry. The results show that ASIC1a distributed in the proximal tubule with higher level in the renal tubule ischaemic injury both in vivo and in vitro. In vivo, Injection of ASIC1a inhibitor PcTx-1 previous to ischaemia/reperfusion (I/R) operation attenuated renal ischaemic injury. In vitro, HK-2 cells were pre-treated with PcTx-1 before hypoxia, the intracellular concentration of Ca2+ , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca2+ overflow, loss of ∆ψm and apoptosis in HK-2 cells. The results revealed that ASIC1a localized in the proximal tubular and contributed to I/R induced kidney injury. Consequently, targeting the ASIC1a may prove to be a novel strategy for AKI patients.

Neurotrophin receptor p75 mediates amyloid ß-induced tau pathology.

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

The ProNGF/p75NTR pathway induces tau pathology and is a therapeutic target for FTLD-tau.

Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3ß pathway. Genetic reduction of p75NTR in P301L mice rescued the memory deficits, alleviated tau hyperphosphorylation and restored the activity of the AKT/GSK3ß pathway. Treatment of the P301L mice with the soluble p75NTR extracellular domain (p75ECD-Fc), which can antagonize neurotoxic ligands of p75NTR, effectively improved memory behavior and suppressed tau pathology. This suggests that p75NTR plays a crucial role in tau paGSKthology and represents a potential druggable target for FTLD-tau and related tauopathies.

Physiological clearance of tau in the periphery and its therapeutic potential for tauopathies.

Accumulation of pathological tau is the hallmark of Alzheimer's disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unknown. Here, we found that cisterna magna injected 131I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than those in femoral artery in humans. These findings suggest that tau proteins can efflux out of the brain and be cleared in the periphery under physiological conditions. Next, we showed that lowering blood tau levels via peritoneal dialysis could reduce interstitial fluid (ISF) tau levels in the brain, and tau levels in the blood and ISF were dynamically correlated; furthermore, tau efflux from the brain was accelerated after the addition of another set of peripheral system in a parabiosis model. Finally, we established parabiosis mouse models using tau transgenic mice and their wild-type littermates and found that brain tau levels and related pathologies in parabiotic transgenic mice were significantly reduced after parabiosis, suggesting that chronic enhancement of peripheral tau clearance alleviates pathological tau accumulation and neurodegeneration in the brain. Our study provides the first evidence of physiological clearance of brain-derived pathological tau in the periphery, suggesting that enhancing peripheral tau clearance is a potential therapeutic strategy for tauopathies.

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Skin Lesion Analysis towards Melanoma Detection Using Deep Learning Network.

Skin lesions are a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of melanoma is extremely challenging due to the following reasons: low contrast between lesions and skin, visual similarity between melanoma and non-melanoma lesions, etc. Hence, reliable automatic detection of skin tumors is very useful to increase the accuracy and efficiency of pathologists. In this paper, we proposed two deep learning methods to address three main tasks emerging in the area of skin lesion image processing, i.e., lesion segmentation (task 1), lesion dermoscopic feature extraction (task 2) and lesion classification (task 3). A deep learning framework consisting of two fully convolutional residual networks (FCRN) is proposed to simultaneously produce the segmentation result and the coarse classification result. A lesion index calculation unit (LICU) is developed to refine the coarse classification results by calculating the distance heat-map. A straight-forward CNN is proposed for the dermoscopic feature extraction task. The proposed deep learning frameworks were evaluated on the ISIC 2017 dataset. Experimental results show the promising accuracies of our frameworks, i.e., 0.753 for task 1, 0.848 for task 2 and 0.912 for task 3 were achieved.

Emodin Inhibits ATP-Induced Proliferation and Migration by Suppressing P2Y Receptors in Human Lung Adenocarcinoma Cells.

BACKGROUND/AIMS: Extracellular ATP performs multiple important functions via activation of P2 receptors on the cell surface. P2Y receptors play critical roles in ATP evoked response in human lung adenocarcinoma cells (A549 cells). Emodin is an anthraquinone derivative originally isolated from Chinese rhubarb, possesses anticancer properties. In this study we examined the inhibiting effects of emodin on proliferation, migration and epithelial-mesenchymal transition (EMT) by suppressing P2Y receptors-dependent Ca2+ increase and nuclear factor-κB (NF-KB) signaling in A549 cells. METHODS: A549 cells were pretreated with emodin before stimulation with ATP for the indicated time. Then, intracellular Ca2+ concentration ([Ca2+]i) was measured by Fluo-8/AM staining. Cell proliferation and cell cycle progression were tested by CCK8 assay and flow cytometry In addition, wound healing and western blot were performed to determine cell migration and related protein levels (Bcl-2, Bax, claudin-1, NF-κB). RESULTS: Emodin blunted ATP/UTP-induced increase of [Ca2+]i and cell proliferation concentration-dependently Meanwhile, it decreased ATP-induced cells accumulation in the S phase. Furthermore, emodin altered protein abundance of Bcl-2, Bax and claudin-1 and attenuated EMT caused by ATP. Such ATP-induced cellular reactions were also inhibited by a nonselective P2Y receptors antagonist, suramin, in a similar way to emodin. Besides, emodin could inhibit activation of NF-κB, thus suppressed ATP-induced proliferation, migration and EMT. CONCLUSION: Our results demonstrated that emodin inhibits ATP-induced proliferation, migration, EMT by suppressing P2Y receptors-mediated [Ca2+]i increase and NF-κB signaling in A549 cells.

Peritoneal dialysis reduces amyloid-beta plasma levels in humans and attenuates Alzheimer-associated phenotypes in an APP/PS1 mouse model.

Clearance of amyloid-beta (Aß) from the brain is an important therapeutic strategy for Alzheimer's disease (AD). Current studies mainly focus on the central approach of Aß clearance by introducing therapeutic agents into the brain. In a previous study, we found that peripheral tissues and organs play important roles in clearing brain-derived Aß, suggesting that the peripheral approach of removing Aß from the blood may also be effective for AD therapy. Here, we investigated whether peritoneal dialysis, a clinically available therapeutic method for chronic kidney disease (CKD), reduces brain Aß burden and attenuates AD-type pathologies and cognitive impairments. Thirty patients with newly diagnosed CKD were enrolled. The plasma Aß concentrations of the patients were measured before and after peritoneal dialysis. APP/PS1 mice were subjected to peritoneal dialysis once a day for 1 month from 6 months of age (prevention study) or 9 months of age (treatment study). The Aß in the interstitial fluid (ISF) was collected using microdialysis. Behavioural performance, long-term potentiation (LTP), Aß burden and other AD-type pathologies were measured after 1 month of peritoneal dialysis. Peritoneal dialysis significantly reduced plasma Aß levels in both CKD patients and APP/PS1 mice. Aß levels in the brain ISF of APP/PS1 mice immediately decreased after reduction of Aß in the blood during peritoneal dialysis. In both prevention and treatment studies, peritoneal dialysis substantially reduced Aß deposition, attenuated other AD-type pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, and synaptic dysfunction, and rescued the behavioural deficits of APPswe/PS1 mice. Importantly, the Aß phagocytosis function of microglia was enhanced in APP/PS1 mice after peritoneal dialysis. Our study suggests that peritoneal dialysis is a promising therapeutic method for AD, and Aß clearance using a peripheral approach could be a desirable therapeutic strategy for AD.

Inhibition of Metabotropic Glutamate Receptor Subtype 1 Alters the Excitability of the Commissural Pyramidal Neuron in the Rat Anterior Cingulate Cortex after Chronic Constriction Injury to the Sciatic Nerve.

BACKGROUND: Inhibition of the metabotropic glutamate receptor subtype 1 in the anterior cingulate cortex has an analgesic effect during sustained nociceptive hypersensitivity. However, the specific changes in different subtypes of anterior cingulate cortex layer 5 pyramidal neurons, as well as the distinct effect of metabotropic glutamate receptor subtype 1 inhibition on different neuronal subtypes, have not been well studied. METHODS: Retrograde labeling combined with immunofluorescence, whole cell clamp recording, and behavioral tests combined with RNA interference were performed in a rat model of chronic constriction injury to the sciatic nerve. RESULTS: Commissural layer 5 pyramidal neurons (projecting to the contralateral cortex) existed in the anterior cingulate cortex. The voltage-gated potassium channel subunit 2-mediated current in these neurons were substantially reduced after chronic constriction injury (current densities at +30 mV for the sham, and chronic constriction injury neurons were [mean ± SD] 10.22 ± 3.42 pA/pF vs. 5.58 ± 2.71 pA/pF, respectively; n = 11; P < 0.01), which increased the spike width and fast afterhyperpolarization potential, resulting in hyperexcitability. Inhibition of metabotropic glutamate receptor subtype 1 alleviated the down-regulation of voltage-gated potassium channel subunit 2 currents (current density increased by 8.11 ± 3.22 pA/pF; n = 7; P < 0.01). Furthermore, knockdown of voltage-gated potassium channel subunit 2 current in the commissural neurons attenuated the analgesic effect of metabotropic glutamate receptor subtype 1 inhibition (n = 6 rats; P < 0.05). CONCLUSIONS: The effect of metabotropic glutamate receptor subtype 1 inhibition on commissural anterior cingulate cortex layer 5 pyramidal neurons is likely different with the modification of previously studied hyperpolarization-activated/cyclic nucleotide-gated channel-dependent neurons but relies on the alteration of voltage-gated potassium channel subunit 2 currents. These results will contribute to a better understanding of the therapeutic role of metabotropic glutamate receptor subtype 1 in chronic pain.

Active AU Based Patch Weighting for Facial Expression Recognition.

Facial expression has many applications in human-computer interaction. Although feature extraction and selection have been well studied, the specificity of each expression variation is not fully explored in state-of-the-art works. In this work, the problem of multiclass expression recognition is converted into triplet-wise expression recognition. For each expression triplet, a new feature optimization model based on action unit (AU) weighting and patch weight optimization is proposed to represent the specificity of the expression triplet. The sparse representation-based approach is then proposed to detect the active AUs of the testing sample for better generalization. The algorithm achieved competitive accuracies of 89.67% and 94.09% for the Jaffe and Cohn-Kanade (CK+) databases, respectively. Better cross-database performance has also been observed.

A multigene phylogentic analysis of Potato virus Y and its application in strain identification.

The objective of this study is to develop a rapid and accurate multigene phylogenetic analysis to identify Potato virus Y (PVY) strains. The phylogenetic relationships of strains within the PVY species were evaluated with isolate-strain association using five datasets of concatenated sequences from the P1, HC-pro, VPg and CP genes to determine the best dataset for PVY strain identification. Results from phylogenetic analyses and Bayesian tip-association significance (BaTS) tests indicated that the major PVY strains could be distinguished using the P1, VPg and CP concatenated sequences datasets but not the remaining concatenated sequence datasets. Phylogenetic trees reconstructed from the concatenated sequences of P1, VPg and CP genes revealed that the ML and NJ trees had broadly similar topologies and that both were better than the maximum clade credibility tree (MCC). Additionally, the full genome of HLJ26, one isolate randomly selected for the multigene phylogenetic analysis, was clustered with high confidence among members of the PVYNTN-NW (SYR-Ⅱ) strain, which includes isolates of SYR-Ⅱ-2-8, SYR-Ⅱ-Be1 and SYR-Ⅱ-DrH. This suggests that it was a PVYNTN-NW (SYR-Ⅱ) isolate. Recombination analysis of this isolate identified four putative recombination joints in the P1, HC-pro/P3, VPg and the 5'-terminus of CP. This pattern is similar to that observed in the genomic structure of PVYNTN-NW (SYR-I), supporting the classification of this isolate as the PVYNTN-NW strain (SYR-Ⅱ). Simultaneously, two expected fragments of approximately 1 000 and 400 bp in size were also amplified from the isolate by a multiplex RT-PCR, consistent with the expected band pattern of the PVYNTN-NW (SYR-Ⅱ) strain. This further supports the utility of the multigene phylogenetic method in identifying PVY strains. We propose that the major PVY strains could be distinguished accurately using multigene phylogenetic analysis based on the concatenated sequences from the P1, VPg and CP genes.