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Highlights • Mobile phone addiction was significantly and positively associated with psychological distress. • Rumination mediated the association between mobile phone addiction and psychological distress. • The direct effect of mobile phone addiction on psychological distress could be moderated by the capacity to be alone. • The capacity to be alone could also act as a buffer in the indirect effect of mobile phone addiction on psychological distress via rumination. • Both the direct effect and indirect effect of mobile phone addiction on psychological distress were stronger for adolescents with lower level of capacity to be alone., Background With the increasing incidence of mobile phone addiction, mobile phone addiction has been considered to be related to adolescents’ psychological distress. However, the underlying mechanisms of this relation were still unclear. The present study tested the mediating role of rumination and the moderating role of the capacity to be alone in the relation between mobile phone addiction and psychological distress. Methods 754 middle school students were recruited to complete measures of mobile phone addiction, rumination, the capacity to be alone, psychological distress and demographic variables. Results Mobile phone addiction was significantly and positively associated with psychological distress, and this link could be mediated by rumination. Moreover, the direct effect of mobile phone addiction on psychological distress and the indirect effect of rumination in this link were moderated by the capacity to be alone. Both these two effects were stronger for adolescents with lower capacity to be alone. Limitations The present study is limited in terms of its sample selection, cross-sectional design, and self-reported instruments. Conclusions The present study advances our understanding of how and when or for whom mobile phone addiction is related to serious psychological distress. Education professionals and parents should pay special attention to the psychological distress of adolescents suffering from mobile phone addiction, particularly for those with lower capacity to be alone.

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.

Researchers have developed various versions of scales to measure mobile phone addiction. Existing scales, however, focus primarily on the overall level of mobile phone addiction but do not distinguish the potential differences between different types of mobile phone addiction. There is a lack of established scales that can measure different types of mobile phone addiction. The present study aimed to uncover the specific types of mobile phone addiction and develop a Mobile Phone Addiction Type Scale (MPATS) for adolescents and young adults. Adolescents and young adults from two high schools and two universities in Central and South China participated in our study. A total of 108 mobile phone addicts (Mage = 17.60 years, SD = 3.568 years; 60.185% males) were interviewed to uncover the specific types of mobile phone addiction. Data from 876 adolescents and young adults (Mage = 16.750 years, SD = 3.159 years; 49.087% males) were tested for item discrimination and exploratory factor analysis. Data from 854 adolescents and young adults (Mage = 16.750 years, SD = 3.098 years; 50.820% males) were analyzed for construct validity, convergent validity, criterion-related validity, and internal consistency reliability. The 26-item Mobile Phone Addiction Type Scale (MPATS) was developed with four factors named mobile social networking addiction, mobile game addiction, mobile information acquisition addiction, and mobile short-form video addiction. The four-factor, 26-item MPATS revealed good construct validity, convergent validity, criterion-related validity, and internal consistency reliability. The new scale is suitable for measuring different types of mobile phone addiction in adolescents and young adults. Limitations and implications are discussed.

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APC) and play pivotal roles in the enhancement or regulation of antiviral immune reactions. Aim of the present study was to investigate whether an HBV-infected maternal environment might influence the infants’ DC phenotype and function. Monocyte-derived DC (MoDC) of neonates born to HBsAg-positive mothers were studied phenotypically by Flow Cytometry (FCM) and functionally by mixed lymphocyte reaction (MLR) and enzyme-linked immunosorbent assay (ELISA). An electron microscope was used to analyze the morphological changes of MoDC. MoDC from neonates whose maternal HBV DNA was>5×107 copies/ml showed a reduced surface expression of CD80, CD86, and HLA-DR as compared to that in neonates whose maternal HBV DNA was negative (CD80: t=3.238, P=0.002; CD86: t=3.543, P=0.001; HLA-DR: t=2.785, P=0.008). T-cell proliferation assays also showed an impaired allostimulatory capacity in comparison to that in neonates whose maternal HBV DNA was negative, especially in the cultures at a DC: T cell ratios of 1:5 and 1:10 (t=-5.442, P

NIRS was used to predict the amino acid profile of freeze-dried pork samples. Samples (150; Longissimus thoracis et lumborum) of pork were used for analysis. After freeze drying, samples were analyzed using HPLC to find out the amino acid content. Samples were scanned and partial least squares (PLS) regression methods were used to predict the amino acid. The determination coefficient obtained by full cross-validated (80 as a sample for calibration set, 25 samples as a validation set) PLS models indicated that the NIR original spectra had an excellent ability to predict the contents of alanine, proline and methionine. Prediction of glutamic acid and glycine using standard normalized variate (SNV) pretreatment of spectral modeling was accurate. Similarly, prediction of arginine,tyrosine, valine, isoleucine, leucine, phenylalanine and lysine were accurate using SNV or multiplicative scattering correction (MSC) pre-processing spectra modeling. It was not possible to predict aspartic acid, serine, threonine, cystine, and histidine. These results indicated that the NIRS can be used for prediction of selected amino acids in the freeze dried pork.

Temporomandibular joint (TMJ) ankylosis in growing patients can cause both mouth opening limitation and jaw bone deformity. Lateral arthroplasty (LAP) can restore the medially displaced condyle and thus keep its growth potential. But can the condyle grow as normal is unknown. This study was to evaluate the long-term result after LAP in growing children. Patients from 2010 to 2014 were evaluated. Their CT data within 1 week after operation and during at least 1-year follow-ups were measured by ProPlan CMF 1.4 software. The condyle-ramus length of both sides and angles and the chin deviation before and after operation were compared. SPSS 17.0 software was used for statistical analysis. A total of 9 patients with a mean age of 10.2 years were included in the study. The mean follow-up period was 1.94 years. The mean condyle-ramus growth was 2.90 mm in the affected side and 2.50 mm in the unaffected side (P = 0.31). All of the affected side exhibited growth and remodeling of the condyle and ramus. All 9 cases had a mean chin deviation of 3.69 mm before operation and 2.92 mm during follow-ups (P = 0.16). The residual condyle grows after LAP, which can reduce the gravity of jawbone deformity.

The taxonomical identification merely based on morphology is often difficult for ancient remains. Therefore, universal or specific PCR amplification followed by sequencing and BLAST (basic local alignment search tool) search has become the most frequently used genetic-based method for the species identification of biological samples, including ancient remains. However, it is challenging for these methods to process extremely ancient samples with severe DNA fragmentation and contamination. Here, we applied whole-genome sequencing data from 12 ancient samples with ages ranging from 2.7 to 700 kya to compare different mapping algorithms, and tested different reference databases, mapping similarities and query coverage to explore the best method and mapping parameters that can improve the accuracy of ancient mammal species identification. The selected method and parameters were tested using 152 ancient samples, and 150 of the samples were successfully identified. We further screened the BLAST-based mapping results according to the deamination characteristics of ancient DNA to improve the ability of ancient species identification. Our findings demonstrate a marked improvement to the normal procedures used for ancient species identification, which was achieved through defining the mapping and filtering guidelines to identify true ancient DNA sequences. The guidelines summarized in this study could be valuable in archaeology, paleontology, evolution, and forensic science. For the convenience of the scientific community, we wrote a software script with Perl, called AncSid, which is made available on GitHub.

Acute traumatic temporomandibular joint disc displacement (ATDD) and its sequelae are not familiar for most surgeons. This study is to discuss its sequelae in cases without disc reduction after failed conservative treatment. From 2010 to 2015, 26 patients with 34 joints were included in the study. All patients had at least 3 months conservative treatment. Their maximal incisor opening (MIO) was measured during follow-ups and MRI examination was used to check the condylar bone degeneration. The mean follow-up for conservative treatment after admission was 8.69 months, the patients reached an average of 25.7 mm MIO. MRI showed condylar bone intact in 8 joints (23.5%), condylar surface bone destruction (Wilks IV, V stages) in 14 joints (41.2%), and severe bone resorption in 12 joints (35.3%). 15 patients with 23 joints were asked for surgical treatment after a mean conservative treatment of 5.4 months (3–12 months) to improve mouth opening and relieve chronic pain. 12 joints had total joint replacement (TJR). 11 joints had disc repositioning. Their mean MIO before operation was 19.8 mm and significantly improved to 33.9 mm after operation (p = 0.0000). ATDD may cause severe osteoarthritis or ankylosis. Disc repositioning and TJR could significantly improve MIO.

NMDA receptors have been widely reported to be involved in the regulation of synaptic plasticity through effects on long-term potentiation (LTP) and long-term depression (LTD). LTP and LTD have been implicated in learning and memory processes. Besides synaptic plasticity, it is known that the phenomenon of gamma oscillations is critical in cognitive functions. Synaptic plasticity has been widely studied, however it is still not clear, to what degree synaptic plasticity regulates the oscillations of neuronal networks. Two NMDA receptor antagonists, ketamine and memantine, have been shown to regulate LTP and LTD, to promote cognitive functions, and have even been reported to bring therapeutic effects in major depression and Alzheimer’s disease respectively. These compounds allow us to investigate the putative interrelationship between network oscillations and synaptic plasticity and to learn more about the mechanisms of their therapeutic effects. In the present study, we have identified that ketamine and memantine could inhibit LTD, without impairing LTP in the CA1 region of mouse hippocampus, which may underlie the mechanism of these drugs’ therapeutic effects. Our results suggest that NMDA-induced LTD caused a marked loss in the gamma power, and pretreatment with 10 μM ketamine prevented the oscillatory loss via its inhibitory effect on LTD. Our study provides a new understanding of the role of NMDA receptors on hippocampal plasticity and oscillations.

γ-secretase inhibitors (GSIs) have been developed to reduce amyloid-β (Aβ) production for the treatment of Alzheimer's disease by inhibiting the cleavage of amyloid precursor protein (APP). However, cross-inhibitory activity on the processing of Notch can cause adverse reactions. To avoid these undesirable effects, γ-secretase modulators (GSMs) are being developed to selectively reduce toxic Aβ production without perturbing Notch signaling. As it is also known that GSIs can cause a paradoxical increase of plasma Aβ over the baseline after a transient reduction (known as Aβ-rebound), we asked if GSMs would cause a similar rebound and what the potential mechanism might be. Our studies were performed with one GSI (LY-450139) and two chemically distinct GSMs. Although LY-450139 caused Aβ-rebound as expected in rat plasma, the two GSMs did not. Inhibition of APP processing by LY-450139 induced an accumulation of γ-secretase substrates, α- and β-C-terminal fragments of APP, but neither GSM caused such an accumulation. In conclusion, we discover that GSMs, unlike GSIs, do not cause Aβ-rebound, possibly because of the lack of accumulation of β-C-terminal fragments. GSMs may be superior to GSIs in the treatment of Alzheimer's disease not only by sparing Notch signaling but also by avoiding Aβ-rebound.

An automated fluid-transport device for a chip-based capillary electrophoresis system has been developed. The device mainly consists of six peristaltic micropumps, two vacuum micropumps, microvalves, multi-way joints, titanium tubes, and a macro-to-micro connector. Various solutions used for the cleaning and activation of chip channels, and electrophoresis separation, are allowed to automatically transport to chip reservoirs by the electric control module. The performance of the whole system was characterized by the analysis of fluorescein sodium using chip electrophoresis with LED-induced fluorescence detection. The peak-height variation (RSD) was 3.8% in six cycles of analyses. Additionally, compared with conventional manual operation, the developed device can spare 60% time for chip pretreatment. This microdevice offers high-efficiency pretreatment for microchips, thereby resulting in a remarkable improvement of analytical capacity for batch samples.

Eight casing failure modes and 32 risk factors in oil and gas wells are given in this paper. According to the quantitative analysis of the influence degree and occurrence probability of risk factors, the Borda counts for failure modes are obtained with the Borda method. The risk indexes of failure modes are derived from the Borda matrix. Based on the support vector machine (SVM), a casing life prediction model is established. In the prediction model, eight risk indexes are defined as input vectors and casing life is defined as the output vector. The ideal model parameters are determined with the training set from 19 wells with casing failure. The casing life prediction software is developed with the SVM model as a predictor. The residual life of 60 wells with casing failure is predicted with the software, and then compared with the actual casing life. The comparison results show that the casing life prediction software with the SVM model has high accuracy.

The corpus callosum is the largest commissural system in the mammalian brain, but the mechanisms underlying its development are not well understood. Here we report that neuronal activity is necessary for the normal development and maintenance of callosal projections in the mouse somatosensory cortex. We labeled a subpopulation of layer II/III callosal neurons viain uteroelectroporation and traced their axons in the contralateral cortex at different postnatal stages. Callosal axons displayed region- and layer-specific projection patterns within the first 2 weeks postnatally. Prenatal suppression of neuronal excitation was achieved via electroporation-induced overexpression of the inward rectifying potassium channel Kir2.1 in layer II/III cortical neurons. This resulted in abnormal callosal projections with many axons extending beyond layers II–III to terminate in layer I. Others failed to terminate at the border between the primary and secondary somatosensory cortices. Blocking synaptic transmission via expression of the tetanus toxin light chain (TeNT-LC) in these axons produced a more pronounced reduction in the projections to the border region, and the eventual disappearance of callosal projections over the entire somatosensory cortex. When Kir2.1 and TeNT-LC were coexpressed, callosal axon targeting exhibited a more severe phenotype that appeared to represent the addition of the effects produced by individual expression of Kir2.1 and TeNT-LC. These results underscore the importance of activity in regulating the developing neural connections and suggest that neuronal and synaptic activities are involved in regulating different aspects of the development of callosal projection.

The effects of the source of Te and the dispersion of TeO 2 on fabricating Mo–V–Te and Mo–V–Te–Nb mixed metal oxide (MMO) catalysts for propane partial oxidation to acrylic acid (AA) were systematically studied. In order to modify the dispersion of TeO 2 in the preparation medium, wet-milling and ultrasonic-assisted dispersion of TeO 2 were adopted. The selected samples were characterized by means of BET, XRD, ICP/XRF, XPS, SEM, H 2 - and C 3 H 8 -TPR and calorimetric NH 3 adsorption. It was clearly demonstrated that different sources of Te and dispersion of TeO 2 in preparation showed significant impact on the physicochemical properties (phase composition, bulk/surface elemental concentration, reactivity of lattice oxygen, and surface acidity) and catalytic activity of the MMO catalysts. The employment of ultrasonic treatment was proved to be effective for making more active and selective Mo–V–Te/Mo–V–Te–Nb catalysts for the target action.

Aim: N -methyl- D -aspartate receptors (NMDAR) are heteromeric complexes primarily assembled from NR1 and NR2 subunits. In normal conditions, NR2 sub-units assemble into homodimers in the endoplasmic reticulum (ER). These homodimers remain in the ER until they coassemble with NR1 dimers and are trafficked to the cell surface. However, it still remains unclear whether functional homomeric NMDAR exist in physiological or pathological conditions. Methods: We transfected GFP-NR2A alone into HEK293 cells, treated the cells with PKC activator 12-myristate-13 acetate (PMA), and then detected surface NR2A sub-units with a live cell immunostaining method. We also used a series of NR2A mutants with a partial deletion of its C-terminus to identify the regions that are involved in the PMA-mediated surface expression of NR2A subunits. Results: NR2A subunits were expressed on the cell membrane after incubation with PMA (200 nmol/L, 30 min), although no functional NMDA channels were detected after PMA-induced membrane trafficking. Immunostaining with an ER marker also revealed that NR2A subunits were exported from the ER after PMA treatment. Furthermore, the deletion of amino acids between 1149-1347 or 1354-1464 of NR2A inhibited PMA-induced surface expression of NR2A subunits. Conclusion: First, our data suggests that PMA treatment can induce the surface expression of homomeric NR2A subunits. Furthermore, this process is probably mediated by the NR2A C-terminal region between positions 1149 and 1464.

Interactions between neurons and glial cells in the brain may serve important functions in the development, maintenance, and plasticity of neural circuits. Fast neuron-glia synaptic transmission has been found between hippocampal neurons and NG2 cells, a distinct population of macroglia-like cells widely distributed in the brain. We report that these neuron-glia synapses undergo activity-dependent modifications analogous to long-term potentiation (LTP) at excitatory synapses, a hallmark of neuronal plasticity. However, unlike the induction of LTP at many neuron-neuron synapses, both induction and expression of LTP at neuron-NG2 synapses involve Ca 2+ -permeable AMPA receptors on NG2 cells.

Infantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.Stem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction (PCR), immunofluorescent staining and injection into BALB/c-nu mice.HemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC). Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days. After 1 - 2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P0.05).HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.

Background: Open joint procedures using bone anchors have shown clinical and radiograph good success, but post surgical disc position has not been documented with MRI imaging. We have designed a modified technique of using two bone anchors and 2 sutures to reposition the articular discs. This MRI study evaluates the post surgical success of this technique to reposition and stabilize the TMJ articular discs. Methods: Consecutive 81 patients with unilateral TMJ internal derangement (ID) (81 TMJs) were treated between December 1, 2003, and December 1, 2006, at the Department of Oral and Maxillofacial Surgery, Ninth Peoples Hospital, Shanghai, Jiao Tong University School of Medicine. All patients were subjected to magnetic resonance imaging before and one to seven days post surgery to determine disc position using the modified bone anchor technique. Results: Postoperative MRIs (one to seven days) confirm that 77 of 81 joints were identified as excellent results and one joint was considered good for an overall effective rate of 96.3% (78 of 81 joints). Only 3.7% (3 of 81) of the joints were designated as poor results requiring a second open surgery. Conclusions: This procedure has provided successful repositioning of the articular discs in unilateral TMJ ID at one to seven days post surgery. Background The temporomandibular joint (TMJ) is the only diarthrodial joint of the human jaws. The joint is formed by the bony articulations of the mandibular condyle and the temporal bone (glenoid fossa and articular eminence). Interposed between the condyle and the fossa is a piece of dense, avascular fibrous connective tissue, the TMJ disc. This disc divides the joint into superior and inferior joint compartments, which normally do not communicate with each other. The disc and condyle are in a normal anatomic relationship if the posterior band of the disc is located above the condylar head when the mandibular condyle is centrically positioned in the fossa. Because the bilaminar tissue posterior to the disc is relatively weak, TMJ disorders are a relatively common

To evaluate the short-term efficacy and safety of propranolol in the treatment of infantile hemangiomas.Between October 2008 and May 2009, oral propranolol was applied to 58 infants with hemangiomas at a dose of 1.0 - 1.5 mg per kilogram of body weight per day in Linyi, Shandong and Shanghai. There were 19 males and 39 females 1 to 12 months old with a mean age of 4 months. The primary tumor size was 1.5 cm x 1.0 cm to 18.0 cm x 5.0 cm. Twenty-seven were superficial, nine deep-seated and 22 mixed. The tumors were located in head and neck (n = 41), trunk and extremities (n = 12), labium vulvae (n = 2), perianal region (n = 1), perineum (n = 1) and scrotum (n = 1). The patients were hospitalized for 7 to 10 days, continued medication at home and revisited every 2 weeks. The changes of tumor size, texture and color were monitored and recorded at a regular interval. The adverse effects after medication were observed and managed accordingly. The short-term results were evaluated using a 4-point scale system.At 24 hours post-medication, all the tumors decreased in density, color and size. The changes became conspicuous within 5 to 7 days. Seven patients had medication for 2 months, 22 for 3 months, 21 for 4 months and 8 for 5 months. The follow-up period was 5 to 9 months. The overall response was scale I (poor) in 1 patient (1.7%), scale II (moderate) in 12 patients (20.7%), scale III (good) in 35 patients (60.4%) and scale IV (excellent) in 10 patients (17.2%). Statistical analysis showed that the treatment response for deep-seated hemangiomas was significantly better than that for superficial hemangiomas (P0.05), but no significant difference was found among different primary sites (P0.05). The main adverse effects were bradycardia (100%), diarrhea (63.8%) and sleep change (30.2%), which resolved after expectant treatment without any significant sequel. No serious adverse effect was observed.Oral propranolol treatment at a low dose is a safe and effective regimen for infantile proliferating hemangiomas. And it can be used as the first-line therapeutic modality. The short-term efficacy is excellent while the side effects are minimal.

Proper nuclear positioning is important to cell function in many biological processes during animal development. In certain cells, the KASH-domain-containing proteins have been shown to be associated with the nuclear envelope, and to be involved in both nuclear anchorage and migration. We investigated the mechanism and function of nuclear anchorage in skeletal muscle cells by generating mice with single and double-disruption of the KASH-domain-containing genes Syne1 (also known as Syne-1)and Syne2 (also known as Syne-2). We showed that the deletion of the KASH domain of Syne-1 abolished the formation of clusters of synaptic nuclei and disrupted the organization of non-synaptic nuclei in skeletal muscle. Further analysis indicated that the loss of synaptic nuclei in Syne-1 KASH-knockout mice significantly affected the innervation sites and caused longer motor nerve branches. Although disruption of neither Syne-1 nor Syne-2 affected viability or fertility, Syne-1; Syne-2 double-knockout mice died of respiratory failure within 20 minutes of birth. These results suggest that the KASH-domain-containing proteins Syne-1 and Syne-2 play crucial roles in anchoring both synaptic and non-synaptic myonuclei that are important for proper motor neuron innervation and respiration.

The cytoplasmic C-terminal domains of NR2 subunits have been proposed to modulate the assembly and trafficking of NMDA receptors. However, questions remain concerning which domains in the C terminus of NR2 subunits control the assembly of receptor complexes and how the assembled complexes are selectively trafficked through the various cellular compartments such as endoplasmic reticulum (ER) to the cell surface. In the present study, we found that the three amino acid tail after the TM4 region of NR2 subunits is necessary for surface expression of functional NMDA receptors, while truncations with only two amino acids following the TM4 region (NR2 Delta 2) completely eliminated surface expression of the NMDA receptor on co-expression with NR1-1a in HEK293 cells. FRET (fluorescence resonance energy transfer) analysis showed that these NR2 Delta 2 truncations are able to form homomers and heteromers on co-expression with NR1-1a. Furthermore, when NR2 Delta 2 subunits were cotransfected with either the NR1-4a or NR1-1a(AAA) mutant, lacking the ER retention motif (RRR), functional NMDA receptors were detected in the transfected HEK293 cells. Unexpectedly, we found that the replacement of five residues after TM4 with alanines gave results indistinguishable from those of NR2B Delta 5 (EHLFY), demonstrating the short tail following the TM4 of NR2 subunits is not sequence-specific-dependent. Taken together, our results show that the C terminus of the NR2 subunits is not necessary for the assembly of NMDA receptor complexes, whereas a three amino acid long cytoplasmic tail following the TM4 of NR2 subunits is sufficient to overcome the ER retention existing in the C terminus of NR1, allowing the assembled NMDA receptors to reach the cell surface.

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline due to the selective neuronal loss in the cortex and hippocampus of the brains. Generation of human induced pluoripotent stem (hiPS) cells holds great promise for disease modeling and drug discovery in AD. In this study, we used neurons with forebrain marker expression from two unrelated hiPS cell lines. As both populations of neurons were vulnerable to β-amyloid 1–42 (Aβ1–42) aggregates, a hallmark of AD pathology, we used them to investigate cellular mediators of Aβ1–42 toxicity. We observed in neurons differentiated from both hiPS cell lines that Aβ induced toxicity correlated with cell cycle re-entry and was inhibited by pharmacological inhibitors or shRNAs against Cyclin-dependent kinase 2 (Cdk2). As one of the hiPS cell lines has been developed commercially to supply large quantities of differentiated neurons (iCell® Neurons), we screened a chemical library containing several hundred compounds and discovered several small molecules as effective blockers against Aβ1–42 toxicity, including a Cdk2 inhibitor. To our knowledge, this is the first demonstration of an Aβ toxicity screen using hiPS cell-derived neurons. This study provided an excellent example of how hiPS cells can be used for disease modeling and high-throughput compound screening for neurodegenerative diseases.