Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.

Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ(9)-tetrahydrocannabinol (Δ(9)-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ(9)-THC is mediated via CB1 receptor-coupled G protein ßγ subunits. Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ(9)-THC exposures. Ablation of COX-2 also eliminates Δ(9)-THC-impaired hippocampal long-term synaptic plasticity, working, and fear memories. Importantly, the beneficial effects of decreasing ß-amyloid plaques and neurodegeneration by Δ(9)-THC in Alzheimer's disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.

CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity.

The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered is unclear. Here we show that CAMSAP1 plays a decisive role in the neuronal axon identification process by regulating the number of MTs. Neurons lacking CAMSAP1 form a multiple axon phenotype in vitro, while the multipolar-bipolar transition and radial migration are blocked in vivo. We demonstrate that the polarity regulator MARK2 kinase phosphorylates CAMSAP1 and affects its ability to bind to MTs, which in turn changes the protection of MT minus-ends and also triggers asymmetric distribution of MTs. Our results indicate that the polarized MT network in neurons is a decisive factor in establishing axon/dendritic polarity and is initially triggered by polarized signals.

Effect of a Patient-Specific Structural Prior Mask on Electrical Impedance Tomography Image Reconstructions.

Electrical Impedance Tomography (EIT) is a low-cost imaging method which reconstructs two-dimensional cross-sectional images, visualising the impedance change within the thorax. However, the reconstruction of an EIT image is an ill-posed inverse problem. In addition, blurring, anatomical alignment, and reconstruction artefacts can hinder the interpretation of EIT images. In this contribution, we introduce a patient-specific structural prior mask into the EIT reconstruction process, with the aim of improving image interpretability. Such a prior mask ensures that only conductivity changes within the lung regions are reconstructed. To evaluate the influence of the introduced structural prior mask, we conducted numerical simulations with two scopes in terms of their different ventilation statuses and varying atelectasis scales. Quantitative analysis, including the reconstruction error and figures of merit, was applied in the evaluation procedure. The results show that the morphological structures of the lungs introduced by the mask are preserved in the EIT reconstructions and the reconstruction artefacts are decreased, reducing the reconstruction error by 25.9% and 17.7%, respectively, in the two EIT algorithms included in this contribution. The use of the structural prior mask conclusively improves the interpretability of the EIT images, which could facilitate better diagnosis and decision-making in clinical settings.

Critical amino acids in the TM2 of EAAT2 are essential for membrane-bound localization, substrate binding, transporter function and anion currents.

Excitatory amino acid transporter 2 (EAAT2), the gene of which is known as solute carrier family 1 member 2 (SLC1A2), is an important membrane-bound transporter that mediates approximately 90% of the transport and clearance of l-glutamate at synapses in the central nervous system (CNS). Transmembrane domain 2 (TM2) of EAAT2 is close to hairpin loop 2 (HP2) and far away from HP1 in the inward-facing conformation. In the present study, 14 crucial amino acid residues of TM2 were identified via alanine-scanning mutations. Further analysis in EAAT2-transfected HeLa cells in vitro showed that alanine substitutions of these residues resulted in a decrease in the efficiency of trafficking/targeting to the plasma membrane and/or reduced functionality of membrane-bound, which resulted in impaired transporter activity. After additional mutations, the transporter activities of some alanine-substitution mutants recovered. Specifically, the P95A mutant decreased EAAT2-associated anion currents. The Michaelis constant (Km ) values of the mutant proteins L85A, L92A and L101A were increased significantly, whereas R87 and P95A were decreased significantly, indicating that the mutations L85A, L92A and L101A reduced the affinity of the transporter and the substrate, whereas R87A and P95A enhanced this affinity. The maximum velocity (Vmax) values of all 14 alanine mutant proteins were decreased significantly, indicating that all these mutations reduced the substrate transport rate. These results suggest that critical residues in TM2 affect not only the protein expression and membrane-bound localization of EAAT2, but also its interactions with substrates. Additionally, our findings elucidate that the P95A mutant decreased EAAT2-related anion currents. Our results indicate that the TM2 of EAAT2 plays a vital role in the transport process. The key residues in TM2 affect protein expression in the membrane, substrate transport and the anion currents of EAAT2.

Optimal Brassinosteroid Levels Are Required for Soybean Growth and Mineral Nutrient Homeostasis.

Brassinosteroids (BRs) are steroid phytohormones that are known to regulate plant growth and nutrient uptake and distribution. However, how BRs regulate nutrient uptake and balance in legume species is not fully understood. Here, we show that optimal BR levels are required for soybean (Glycine max L.) seedling growth, as treatments with both 24-epicastasterone (24-epiCS) and the BR biosynthesis inhibitor propiconazole (PPZ) inhibit root growth, including primary root elongation and lateral root formation and elongation. Specifically, 24-epiCS and PPZ reduced the total phosphorus and potassium levels in the shoot and affected several minor nutrients, such as magnesium, iron, manganese, and molybdenum. A genome-wide transcriptome analysis identified 3774 and 4273 differentially expressed genes in the root tip after brassinolide and PPZ treatments, respectively. The gene ontology (GO) analysis suggested that genes related to "DNA-replication", "microtubule-based movement", and "plant-type cell wall organization" were highly responsive to the brassinolide and PPZ treatments. Furthermore, consistent with the effects on the nutrient concentrations, corresponding mineral transporters were found to be regulated by BR levels, including the GmPHT1s, GmKTs, GmVIT2, GmZIPs, and GmMOT1 genes. Our study demonstrates that optimal BR levels are important for growth and mineral nutrient homeostasis in soybean seedlings.

Application of genetic screening processor in screening neonatal glucose-6-phosphate dehydrogenase deficiency.

To evaluate the performance of genetic screening processor (GSP analyzer) in neonatal screening for glucose-6-phosphate dehydrogenase (G6PD)deficiency. The accuracy and precision of GSP analyzer was evaluated with the control materials from National Center for Clinical Laboratories and the low and high quality G6PD control kit (fluorescence analysis). GSP analyzer and semi-automatic fluorescence immunoanalyzer (1420 analyzer) were simultaneously used to detect 2622 neonatal screening samples and 41 confirmed samples to analyze the correlation and consistency of the test results; 78 floating samples and 78 non-floating samples were detected to compare the result. A total of 1 100 384 neonatal screening samples from January 2017 to December 2018 and 855 856 neonatal screening samples from January 2019 to December 2020 were detected with 1420 analyzer and GSP analyzer, respectively. Referring to the percentile method and the expert consensus, the new cut-off value of GSP analyzer for G6PD deficiency in screening was established. The relative bias of GSP analyzer in detecting G6PD was 0.71%-4.23%; the intra assay precision was 4.34%-4.91%, the inter assay precision was 0.85%-2.12%, and the total coefficient of variation was 5.44%-5.72%. There was a significant positive correlation between G6PD activity detected by GSP analyzer and 1420 analyzer (=0.740, <0.01). Forty-one clinical confirmed patients were identified by both 1420 analyzer and GSP analyzer (=0.945). The G6PD activity in floating dry blood spots detected by 1420 analyzer was significantly lower than that in non-floating dry blood spots (<0.05), but there was no significant difference in G6PD activity between floating and non-floating dry blood spots detected by GSP analyzer (>0.05). The sensitivities of GSP analyzer and 1420 analyzer in screening G6PD deficiency were both 100.00%, and the specificities were both more than 99.80%. Compared with 1420 analyzer, the positive predictive value, positive rate and prevalence of G6PD deficiency detected by GSP analyzer were increased, and the false positive rate was decreased (all <0.01). The new cut-off value was 26.1 U/dL for male and 29.1 U/dL for female according to the 99.1% percentile of the population. GSP analyzer has better detection performance with high automation, efficiency and throughput, which can be used in large-scale screening for neonatal G6PD deficiency.

Microglia depletion exacerbates acute seizures and hippocampal neuronal degeneration in mouse models of epilepsy.

Epileptic seizures are the manifestation of hypersynchronous and excessive neuronal excitation. While the glutamatergic and GABAergic neurons play major roles in shaping fast neuronal excitation/inhibition homeostasis, it is well illustrated that astrocytes profoundly regulate neuronal excitation by controlling glutamate, GABA, cannabinoids, adenosine, and concentration of K+ around neurons. However, little is known about whether microglia take part in the regulation of acute neuronal excitation and ongoing epileptic behaviors. We proposed that if microglia are innately ready to respond to epileptic overexcitation, depletion of microglia might alter neuronal excitability and severity of acute epileptic seizures. We found that microglia depletion by plx3397, an inhibitor of CSF1R, exacerbates seizure severity and excitotoxicity-induced neuronal degeneration, indicating that microglia are rapidly responsive to the change of excitation/inhibition homeostasis and participate in the protection of neurons from overexcitation.

In Vivo Bioimpedance Spectroscopy Characterization of Healthy, Hemorrhagic and Ischemic Rabbit Brain within 10 Hz-1 MHz.

Acute stroke is a serious cerebrovascular disease and has been the second leading cause of death worldwide. Conventional diagnostic modalities for stroke, such as CT and MRI, may not be available in emergency settings. Hence, it is imperative to develop a portable tool to diagnose stroke in a timely manner. Since there are differences in impedance spectra between normal, hemorrhagic and ischemic brain tissues, multi-frequency electrical impedance tomography (MFEIT) shows great promise in detecting stroke. Measuring the impedance spectra of healthy, hemorrhagic and ischemic brain in vivo is crucial to the success of MFEIT. To our knowledge, no research has established hemorrhagic and ischemic brain models in the same animal and comprehensively measured the in vivo impedance spectra of healthy, hemorrhagic and ischemic brain within 10 Hz-1 MHz. In this study, the intracerebral hemorrhage and ischemic models were established in rabbits, and then the impedance spectra of healthy, hemorrhagic and ischemic brain were measured in vivo and compared. The results demonstrated that the impedance spectra differed significantly between healthy and stroke-affected brain (i.e., hemorrhagic or ischemic brain). Moreover, the rate of change in brain impedance following hemorrhagic and ischemic stroke with regard to frequency was distinct. These findings further validate the feasibility of using MFEIT to detect stroke and differentiate stroke types, and provide data supporting for future research.

Activation of glycine receptors modulates spontaneous epileptiform activity in the immature rat hippocampus.

While the expression of glycine receptors in the immature hippocampus has been shown, no information about the role of glycine receptors in controlling the excitability in the immature CNS is available. Therefore, we examined the effect of glycinergic agonists and antagonists in the CA3 region of an intact corticohippocampal preparation of the immature (postnatal days 4-7) rat using field potential recordings. Bath application of 100 µM taurine or 10 µM glycine enhanced the occurrence of recurrent epileptiform activity induced by 20 µM 4-aminopyridine in low Mg(2+) solution. This proconvulsive effect was prevented by 3 µM strychnine or after incubation with the loop diuretic bumetanide (10 µM), suggesting that it required glycine receptors and an active NKCC1-dependent Cl(-) accumulation. Application of higher doses of taurine (≥ 1 mM) or glycine (100 µM) attenuated recurrent epileptiform discharges. The anticonvulsive effect of taurine was also observed in the presence of the GABAA receptor antagonist gabazine and was attenuated by strychnine, suggesting that it was partially mediated by glycine receptors. Bath application of the glycinergic antagonist strychnine (0.3 µM) induced epileptiform discharges. We conclude from these results that in the immature hippocampus, activation of glycine receptors can mediate both pro- and anticonvulsive effects, but that a persistent activation of glycine receptors is required to suppress epileptiform activity. In summary, our study elucidated the important role of glycine receptors in the control of neuronal excitability in the immature hippocampus.

Quantitative proteomics analysis identified new interacting proteins of JAL30 in Arabidopsis.

Jacalin-related lectins (JALs) are a unique group of plant lectins derived from the jacalin protein family, which play important roles in plant defense responses. JAL30/PBP1 (PYK10 binding protein 1) interacts with inactive PYK10, exerting negative regulatory control over the size of the PYK10 complex, which is formed and activated upon insect or pathogen invasion. However, the precise interplay between JAL30 and other components remains elusive. In this study, we found JAL30 as a nucleocytoplasmic protein, but no obvious phenotype was observed in jal30-1 single mutant. Through immunoprecipitation (IP) enrichment combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), dozens of new JAL30 interacting proteins were found in addition to several reported ones. Gene Ontology (GO) analysis revealed that these interacting proteins were highly related to the wounding and bacterial stimuli, suggesting their potential involvement in the jasmonate (JA) response. Importantly, the expression of JAL30 was induced by MeJA treatment, further highlighting its relevance in plant defense mechanisms. A novel JAL30 interacting protein, ESM1, was identified and its interaction with JAL30 was confirmed by Co-immunoprecipitation. Moreover, ESM1 was found as an O-GlcNAcylated protein, suggesting that JAL30 may possess glycosylated protein binding ability, particularly in O-GlcNAcylated protein and peptide recognition. Overall, our study provides valuable insights into the interacting protein network and biological function of JAL30, demonstrates the interaction between JAL30 and ESM1, and uncovers the potential significance of JAL30 in plant defense system, potentially through its association with PYK10 complex or JA response. SIGNIFICANCE: The biological functions of lectin proteins, including defense responses, immunity responses, signal transduction, have been well studied. Lectin proteins were also utilized to enrich glycosylated proteins for their specific carbohydrates binding capability. Jacalin-related lectins (JALs) were found to involve in plant defense mechanism. However, it is not yet clear whether JALs could use for enrichment of glycosylated proteins. In this study, we used label-free quantification method to identify interacting proteins of JAL30. A novel interacting protein, ESM1, as an O-GlcNAcylated protein was found. ESM1 has been reported to take part in defense against insect herbivory. Therefore, our findings provided experimental evidence to confirm that JALs have potential to be developed as the bio-tools to enrich glycosylated proteins. Finally, our data not only illustrated the vital biological role of JALs in plants, but also verified unique function of JAL30 in recognizing O-GlcNAcylated proteins.

Anti-CRMP2 antibody induces anxiety-like behavior and increases pyramidal neuron excitability in mice.

BACKGROUND: We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab. METHODS: Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes. RESULTS: The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected. CONCLUSION: In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab.

Quantitative proteomics of the miR-301a/SOCS3/STAT3 axis reveals underlying autism and anxiety-like behavior.

Autism is a widespread neurodevelopmental disorder. Although the research on autism spectrum disorders has been increasing in the past decade, there is still no specific answer to its mechanism of action and treatment. As a pro-inflammatory microRNA, miR-301a is abnormally expressed in various psychiatric diseases including autism. Here, we show that miR-301a deletion and inhibition exhibited two distinct abnormal behavioral phenotypes in mice. We observed that miR-301a deletion in mice impaired learning/memory, and enhanced anxiety. On the contrary, miR-301a inhibition effectively reduced the maternal immune activation (MIA)-induced autism-like behaviors in mice. We further demonstrated that miR-301a bound to the 3'UTR region of the SOCS3, and that inhibition of miR-301a led to the upregulation of SOCS3 in hippocampus. The last result in the reduction of the inflammatory response by inhibiting phosphorylation of AKT and STAT3, and the expression level of IL-17A in poly(I:C)-induced autism-like features in mice. The obtained data revealed the miR-301a as a critical participant in partial behavior phenotypes, which may exhibit a divergent role between gene knockout and knockdown. Our findings ascertain that miR-301a negatively regulates SOCS3 in MIA-induced autism in mice and could present a new therapeutic target for ameliorating the behavioral abnormalities of autism.

Pulmonary function testing dataset of pressure and flow, dynamic circumference, heart rate, and aeration monitoring.

Respiratory data was collected from 20 subjects, with an even sex distribution, in the low-risk clinical unit at the University of Canterbury. Ethical consent for this trial was granted by the University of Canterbury Human Research Ethics Committee (Ref: HREC 2023/30/LR-PS). Respiratory data were collected, for each subject, over three tests consisting of: 1) increasing set PEEP from a starting point of ZEEP using a CPAP machine; 2) test 1 repeated with two simulated apnoea's (breath holds) at each set PEEP; and 3) three forced expiratory manoeuvres at ZEEP. Data were collected using a custom pressure and flow sensor device, ECG, PPG, Garmin HRM Dual heartrate belt, and a Dräeger PulmoVista 500 Electrical Impedance Tomography (EIT) machine. Subject demographic data was also collected prior to the trial, in a questionnaire, with measurement equipment available. These data aim to inform the development of pulmonary mechanics models and titration algorithms.

Respiratory monitoring dataset, with rapid expiratory occlusions, over increasing positive airway pressure ventilation.

Resting breathing data was collected from 80 smokers, vapers, asthmatics, and otherwise healthy people in the low-risk clinical unit at the University of Canterbury. Subjects were asked to breathe normally through a full-face mask connected to a Fisher and Paykel Healthcare SleepStyle SPSCAA CPAP device. PEEP (Positive End-Expiratory Pressure) support was increased from 4 to 12 cmH2O in 0.5 cmH2O increments. Data was also collected during resting breathing at ZEEP (0 cmH2O) before and after the PEEP trial. The trial was conducted under University of Canterbury Human Research Ethics Committee consent (Ref: HREC 2023/04/LR-PS). Data was collected by and Dräeger PulmoVista 500 EIT machine and a custom Venturi-based pressure and flow sensor device connected in series with the CPAP and full-face mask. The outlined dataset includes pressure, flow, volume, dynamic circumference (thoracic and abdominal, and cross-sectional aeration. Subject demographic data was self-reported using a questionnaire given prior to the trial.

Microporous melamine-formaldehyde networks loaded on rice husks for dynamic removal of organic micropollutants.

The alteration of agricultural wastes into novel adsorbents can stimulate their scalability in realistic application, showing great economic and environmental advantages. Here, we proposed a strategy to engineer rice husk (RH) with microporous melamine-formaldehyde networks (MFNs) resins and the utilization for dynamic removal of organic micropollutants rapidly and efficiently. was pre-treated to acquire attractive surface and unique hierarchical porosity, endowing with surface functionalization and essential filtering properties. MFNs can be uniformly generated in-situ on the fully exposed cellulose backbones of the pre-treated RH. MFNs granules functionalized RH (RH@MFNs) exhibited high removal efficiencies over 90% within 30 min for the adsorption of hazardous organic compounds (e.g., phenolic and antibiotic micropollutants) in static tests. Experiment results and density functional theory (DFT) simulation revealed that the synergy of hydrogen bonding, π-πinteraction, and micropore preservation dominates the adsorption. Further dynamic adsorption experiments showed that the removal efficiency and equilibrium removal capacity towards bisphenol A by RH@MFNs packed bed up-flow column were 2.6 and 67 times higher than that of raw RH, respectively. The column adsorption fits well with the Thomas model and bed depth service time (BDST) kinetic model. The inherent macropores inside RH and the roughness caused by the spiky structures and mesopores outside RH, as well as the accumulated MFNs granules, can lead to local turbulence of water flow around RH@MFNs, enabling fast and efficient adsorption. This sustainable and cost-effective preparation of RH-based adsorbents sheds light on the rational design of biomass waste adsorbents for realistic wastewater.

Structural priors represented by discrete cosine transform improve EIT functional imaging.

Structural prior information can improve electrical impedance tomography (EIT) reconstruction. In this contribution, we introduce a discrete cosine transformation-based (DCT-based) EIT reconstruction algorithm to demonstrate a way to incorporate the structural prior with the EIT reconstruction process. Structural prior information is obtained from other available imaging methods, e.g., thorax-CT. The DCT-based approach creates a functional EIT image of regional lung ventilation while preserving the introduced structural information. This leads to an easier interpretation in clinical settings while maintaining the advantages of EIT in terms of bedside monitoring during mechanical ventilation. Structural priors introduced in the DCT-based approach are of two categories in terms of different levels of information included: a contour prior only differentiates lung and non-lung region, while a detail prior includes information, such as atelectasis, within the lung area. To demonstrate the increased interpretability of the EIT image through structural prior in the DCT-based approach, the DCT-based reconstructions were compared with reconstructions from a widely applied one-step Gauss-Newton solver with background prior and from the advanced GREIT algorithm. The comparisons were conducted both on simulation data and retrospective patient data. In the simulation, we used two sets of forward models to simulate different lung conditions. A contour prior and a detail prior were derived from simulation ground truth. With these two structural priors, the reconstructions from the DCT-based approach were compared with the reconstructions from both the one-step Gauss-Newton solver and the GREIT. The difference between the reconstructions and the simulation ground truth is calculated by the ℓ2-norm image difference. In retrospective patient data analysis, datasets from six lung disease patients were included. For each patient, a detail prior was derived from the patient's CT, respectively. The detail prior was used for the reconstructions using the DCT-based approach, which was compared with the reconstructions from the GREIT. The reconstructions from the DCT-based approach are more comprehensive and interpretable in terms of preserving the structure specified by the priors, both in simulation and retrospective patient data analysis. In simulation analysis, the ℓ2-norm image difference of the DCT-based approach with a contour prior decreased on average by 34% from GREIT and 49% from the Gauss-Newton solver with background prior; for reconstructions of the DCT-based approach with detail prior, on average the ℓ2-norm image difference is 53% less than GREIT and 63% less than the reconstruction with background prior. In retrospective patient data analysis, the reconstructions from both the DCT-based approach and GREIT can indicate the current patient status, but the DCT-based approach yields more interpretable results. However, it is worth noting that the preserved structure in the DCT-based approach is derived from another imaging method, not from the EIT measurement. If the structural prior is outdated or wrong, the result might be misleadingly interpreted, which induces false clinical conclusions. Further research in terms of evaluating the validity of the structural prior and detecting the outdated prior is necessary.

Influence of a Structural Prior Mask on EIT Image Reconstruction.

Electrical Impedance Tomography (EIT) is a low-cost imaging method with promising results in visualizing ventilation distribution within the lungs. However, in clinical settings, the interpretability of EIT images is often limited by blurred anatomical alignment and reconstruction artifacts. Integrating structural priors into the EIT reconstruction process can enhance the interpretability of EIT images. In this contribution, we introduced a patient-specific structural prior mask into the EIT reconstruction process. Such prior mask ensures that only conductivity changes within the lung regions are reconstructed. With the aim to investigate the influence of the structural prior mask on the EIT images, we conducted numerical simulations in terms of four different ventilation status. EIT images were reconstructed with Gauss-Newton algorithm and discrete cosine transform-based EIT algorithm. We carried out quantitative analysis including the reconstruction error and figures of merit for the evaluation. The results show that the morphological structures of the lungs introduced by the prior mask are preserved in the EIT images, and the reconstruction artefacts are also limited. In conclusion, the incorporation of the structural prior mask enhances the interpretability of EIT images in clinical settings.Clinical relevance-The correct interpretation of an EIT image is crucial for a clinical diagnosis. This research demonstrates that a structural prior mask might have the potential to improve the interpretability of an EIT image, which facilitates the clinicians with a better understanding of EIT results.

A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions.

Down syndrome (DS) is caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is the most common genetic cause for developmental cognitive disability. The regions on Hsa21 are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this report, we describe a new mouse model for DS that carries duplications spanning the entire Hsa21 syntenic regions on all three mouse chromosomes. This mouse mutant exhibits DS-related neurological defects, including impaired cognitive behaviors, reduced hippocampal long-term potentiation and hydrocephalus. These results suggest that when all the mouse orthologs of the Hsa21 genes are triplicated, an abnormal cognitively relevant phenotype is the final outcome of the elevated expressions of these orthologs as well as all the possible functional interactions among themselves and/or with other mouse genes. Because of its desirable genotype and phenotype, this mutant may have the potential to serve as one of the reference models for further understanding the developmental cognitive disability associated with DS and may also be used for developing novel therapeutic interventions for this clinical manifestation of the disorder.

Dopaminergic modulation of low-Mg²âº-induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro.

To investigate whether epileptiform activity in the immature brain is modulated by dopamine, we examined the effects of dopaminergic agonists and antagonists in an intact in vitro preparation of the isolated corticohippocampal formation of immature (postnatal days 3 and 4) C57/Bl6 mice using field potential recordings from CA3. Epileptiform discharges were induced by a reduction of the extracellular Mg(2+) concentration to 0.2 mM. These experiments revealed that low concentrations of dopamine (<0.3 µM) attenuated epileptiform activity, whereas >3 µM dopamine enhanced epileptiform activity. The D1-agonist SKF38393 (10 µM) had a strong proconvulsive effect, and the D2-like agonist quinpirole (10 µM) mediated a weak anticonvulsive effect. The proconvulsive effect of 10 µM dopamine was completely abolished by the D1-like receptor antagonist SCH39166 (2 µM) or the D2-like antagonist sulpiride (10 µM), whereas the D2 antagonist L-741626 (50 nM) and the D3 antagonist SB-277011-A (0.1 µM) were without effect. The anticonvulsive effect of 0.1 µM dopamine could be suppressed by D1-like, D2, or D3 receptor antagonists. A proconvulsive effect of 10 µM dopamine was also observed when AMPA, NMDA, or GABA(A) receptors were blocked. In summary, these results suggest that 1) dopamine influences epileptiform activity already at early developmental stages; 2) dopamine can bidirectionally influence the excitability; 3) D1-like receptors mediate the proconvulsive effect of high dopamine concentrations, although the pharmacology of the anticonvulsive effect is less clear; and 4) dopamine-induced alterations in GABAergic and glutamatergic systems may contribute to this effect.

Influence of hyperparameter on the Untrue Prior Detection in Discrete Transformation-based EIT Algorithm.

Incorporated with a structural prior, discrete cosine transformation (DCT) based electrical impedance tomog-raphy (EIT) algorithm can improve the interpretability of EIT images in clinical settings. However, this benefit comes with a risk of the untrue prior which yields a misleading result compromising clinical decision. The redistribution index is able to detect an untrue prior by analysing EIT reconstructions. In addition to structural priors, EIT reconstruction is also affected by the choice of hyperparameter A in DCT-based EIT algorithm. In this research, influence of hyperparameter on untrue prior detection is investigated in terms of simulation experiment. A series of simulation settings consisting of 30 different atelectasis scales was conducted, then reconstructed with 20 different hyperparameters, to investigate the behavior of redistribution index. The result shows, despite the fact that redistribution index is indeed influenced by the choice of the hyperparameter A, the detection of an untrue prior is not significantly affected. The untrue prior detection is rather stable regardless of the optimal hyperparameter. Clinical Relevance - Optimal hyperparameter is not always guaranteed in clinical settings. This research confirms that the untrue prior detection is not strongly influenced by the hyperparameter. An update of untrue priors incorporated into EIT approach will facilitate a better interpretation of EIT results and an accurate clinical decision.