Effects of Curcumin Treatment in a Diabetic Neuropathic Pain Model of Rats: Involvement of c-Jun N-Terminal Kinase Located in the Astrocytes and Neurons of the Dorsal Root Ganglion.

Curcumin (diferuloylmethane) is a major component of turmeric, which is isolated from the rhizomes of Curcuma longa L. from the family Zingiberaceae. It is used as a dietary pigment for curry and in traditional Indian medicine for its anti-inflammatory and attenuating pain effects. This study aimed to evaluate the beneficial effects of curcumin in a rat model of diabetic neuropathic pain. Additionally, we investigated the involvement of the phosphorylated form of c-Jun N-terminal kinase (pJNK) located in the neurons and astrocytes of the dorsal root ganglion (DRG). To induce diabetic neuropathic pain in rats, 50 mg/kg of streptozotocin (STZ) was intraperitoneally injected. After 4 weeks, rats were administered the vehicle, 10 mg/kg/day curcumin, or 50 mg/kg/day curcumin orally for 4 consecutive weeks. One day after the final drug administration, we performed behavioral tests to measure responses of rats to mechanical, heat, cold, and acetone-induced cold stimuli. After behavioral tests, pJNK expression in the DRG was evaluated using western blot assay and immunohistochemistry. Curcumin treatment for 4 consecutive weeks in STZ-induced diabetic neuropathic pain rats improved behavioral responses to mechanical, cold, and thermal stimuli. Increased pJNK expression in the astrocytes and neurons of the DRG in STZ-induced diabetic neuropathic pain rats was reduced by curcumin treatment for 4 consecutive weeks. We suggest that curcumin can be an option for the treatment of diabetes-related neuropathic pain, and one of the mechanisms that underlie the action of curcumin may involve pJNK expression in the astrocytes and neurons of the DRG.

Negative pressure pulmonary edema in a patient undergoing open rhinoplasty: A case report.

RATIONALE: Negative pressure pulmonary edema (NPPE) is associated with serious postoperative complications. Compact nasal packing is always done after an open rhinoplasty procedure which makes it difficult to achieve positive pressure ventilation via a mask if NPPE arises. PATIENT CONCERNS: A 21-year-old healthy man got an open rhinoplasty, septal perforation repair, and revisional septal reconstruction. After surgery, he became so agitated that it was difficult to calm him. We decided to remove the endotracheal tube. On arrival at the post-anesthesia care unit, he was cyanotic and his SpO2 had decreased to about 2%. We attempted positive pressure ventilation using mask bagging; however, it was ineffective due to the nasal packing. DIAGNOSES: Negative pressure pulmonary edema. INTERVENTIONS: Emergent reintubation was immediately done and Ambu bagging was commenced. A considerable pinkish secretion came out of the tube. A T-piece was applied to him using 15 L/min of oxygen supply. The patient was eventually transferred to the intensive care unit of our hospital. OUTCOMES: On postoperative day (POD) 1, a decision was made to extubate, and the oxygen supply was shifted to 3L/min using a venturi-mask. On POD 2, a chest posteroanterior radiograph was taken and indicated no active lung lesion. The patient was subsequently discharged without any complications. He had no symptoms on POD 6, 11, and 18 at follow-up visits to our outpatient clinic. LESSONS: Anesthesiologists should be alert to the possibility of NPPE and its treatment because of its rapid onset but positive clinical outcome if there is a proper intervention. In nasal surgery cases in particular, early re-intubation should be conducted and extubation should be done to fully awaken the patients.

New Surface Modification Method To Develop a PET-Based Membrane with Enhanced Ion Permeability and Organic Fouling Resistance for Efficient Production of Marine Microalgae.

This paper presents a new surface modification strategy to develop a poly(ethylene terephthalate) (PET)-based membrane having a hydrophilic surface, high nutrient ion permeability, sufficient mechanical strength, and organic fouling resistance, using an anthracene (ANT)-attached polyethylene glycol (PEG) surface modification agent (SMA) synthesized in this work. During the modification process, the ANT parts of the SMAs poke through and anchor to the surface of a commercial PET woven fabric via physical interactions and mechanical locking. The PEG chain parts coat the surface in the brush and arch forms, which generates a hydration layer on the fabric surface. The consequently obtained surface property and unique structure of the modified PET-based membrane result in higher nitrate ion permeability, organic fouling resistance, and microalgae production compared to those of the unmodified one. These are also affected by the molecular weight of the PEG and the number density of the anchored SMAs. The study demonstrates that this new surface modification method has the potential to allow the development of a desirable PET-based membrane for the efficient massive production of marine microalgae.

Enhanced lipid productivity in AGP knockout marine microalga Tetraselmis sp. using a DNA-free CRISPR-Cas9 RNP method.

A marine green microalga, Tetraselmis sp., has been studied for the production of biomass and lipids in seawater culture. Since carbohydrate and lipid biosynthesis are competitive metabolic pathways, we attempted to increase lipid synthesis in Tetraselmis by inhibiting carbohydrate synthesis. The main regulatory enzyme in the starch synthesis pathway is ADP-glucose pyrophosphorylase (AGP). AGP loss-of-function mutants were developed using the CRISPR-Cas9 ribonucleoprotein (RNP) delivery system. AGP mutants showed a slight decrease in growth. However, the lipid content in two AGP mutants was significantly enhanced by 2.7 and 3.1 fold (21.1% and 24.1% of DCW), respectively, compared to that in the wild type (7.68% of DCW) under nitrogen starvation. This study is an example of metabolic engineering by genetic editing using the CRISPR-Cas9 RNP method in marine green microalgae. Consequently, starchless Tetraselmis mutants might be considered potential producers of lipids in seawater cultures.

Comparison of Nonimage- and Fluoroscopy-Guided Interlaminar Epidural Block: A Matched Paired Analysis in the Same Individuals.

Background: Although fluoroscopic guidance is recommended highly for more accurate lumbar interlaminar epidural steroid injection (L-ESI), many physicians still use a nonimage-guided approach for L-ESIs. However, because of its associated risk of radiation and increased medical expense, the cost-effectiveness and safety of fluoroscopy-guided ESI have been called into question. The goal of this retrospective matched paired analysis in the same individuals was to assess the effectiveness and prevalence of complications of nonimage-guided L-ESI compared to those of fluoroscopy-guided L-ESI. Methods. Between 2015 and 2016, 94 patients who received both nonimage- and fluoroscopy-guided L-ESIs were analyzed retrospectively. The changes of the numeric rating scale (NRS) in pain intensity and functional outcome and the differences in the number of complications between blind and fluoroscopy-guided L-ESIs in the same individuals were evaluated by a matched paired analysis. Results: Of the 94 patients, the differences in NRS before and after the procedure were 1.29 (95% confidence interval (CI) = 0.94-1.65) for the nonimage-guided group and 1.64 (95% CI = 1.28-2.01) for the fluoroscopy-guided group (p=0.16). More subjective functional improvement was observed in fluoroscopy-guided L-ESI (57, 60.6%) than in nonimage-guided L-ESI (47, 50.0%) without statistical significance (p=0.16). Nine (9.6%) patients in the nonimage-guided group experienced complications related to the procedure overall compared to 4 (4.3%) in the fluoroscopy-guided group (p=0.27). Conclusions: In this study, both blind and image-guided L-ESI techniques included similar extents of postprocedural outcomes and complications. Physicians should consider the risks associated with the two different techniques overall and develop ways to individualize the procedure to decrease the risk of complications and improve the positive outcomes of lumbar epidural steroid injections.

Impact of educational levels on survival rate: A cohort study of 2007 living donor liver transplant recipients at a single large center.

Among living donor liver transplantation recipients, the impact of educational levels on survival has rarely explored. Thus, the purpose of study is to analyze the survival rate differences across educational levels among recipients who underwent living donor liver transplantation.We retrospectively analyzed 2007 adult recipients who underwent living donor liver transplantation in a single large center. The educational level was divided into three categories: middle school or lower, high school, and college or higher. The primary outcome was all-cause mortality after living donor liver transplantation. Stratified log-rank test and Cox proportional hazard model were employed for statistical analysis.The incidence rates of all-cause mortality were 23.85, 20.19, and 18.75 per 1000 person-year in recipients with middle school or lower, high school, and college or higher education groups, respectively. However, the gender-stratified log-rank test has not shown a statistically significant difference (P = .3107). In the unadjusted model, hazard ratio (HR) was 1.02 [95% confidence interval (CI) = 0.79-1.33] in high school and 1.23 (95% CI = 0.93-1.64) and in middle school or lower educational level, respectively; In the full adjusted model, the HR of high school was 0.98 (95% CI = 0.75-1.28) and the HR of middle school or lower was 1.01 (95% CI = 0.74-1.37).Although study population of this study is large, we could not find significant survival rate differences by the levels of education. Social selection and high compliance rate might contribute to this result.

Effect of Total Intravenous Anesthesia vs Volatile Induction With Maintenance Anesthesia on Emergence Agitation After Nasal Surgery: A Randomized Clinical Trial.

Importance: Emergence agitation is common after nasal surgery under general anesthesia and may lead to serious consequences for the patient, including an increased risk of injury, pain, hemorrhage, and self-extubation. Despite decades of research, studies on the incidence, risk factors, and prevention of emergence agitation in adult patients are ongoing, and opinions differ on the different effects of inhalation and intravenous anesthesia. Objective: To investigate the effect of anesthetic method on the occurrence of emergence agitation after nasal surgery. Design, Setting, and Participants: This prospective, randomized, single-blind, clinical trial included 80 patients undergoing open rhinoplasty, septoplasty, turbinoplasty, endoscopic sinus surgery, and functional endoscopic sinus surgery under general anesthesia who were randomized to receive total intravenous anesthesia (TIVA) with remifentanil hydrochloride and propofol (n = 40) or volatile induction and maintenance of anesthesia (VIMA) with sevoflurane and nitrous oxide (n = 40) in Asan Medical Center, a tertiary referral center in Seoul, Republic of Korea. Data were collected from August 24 through October 14, 2016, and analyzed from October 26, 2016, through September 14, 2017. Main Outcomes and Measures: The occurrence of emergence agitation defined by the following 2 individual criteria: a Richmond Agitation-Sedation Scale score of at least 1 and a Riker Sedation-Agitation Scale score of at least 5 immediately after extubation. Results: Among the 80 patients included in the analysis (68.8% men [n = 55]; mean [SD] age, 41.6 [17.9] years), emergence agitation measured by the Richmond Agitation Sedation Scale occurred in 8 of 40 patients (20.0%) in the VIMA group and 1 of 40 (2.5%) in the TIVA group. The risk difference was 17.5 (95% CI, 3.6-31.4). Emergence agitation measured by the Riker Sedation-Agitation Scale score occurred in 10 of 40 patients (25.0%) in the VIMA group and 1 of 40 (2.5%) in the TIVA group. The risk difference was 22.5 (95% CI, 7.3-37.7). Conclusions and Relevance: The occurrence of emergence agitation after nasal surgery under general anesthesia can be significantly reduced by using TIVA rather than VIMA. Trial Registration: CRIS identifier: KCT0002145.

Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice.

Autism spectrum disorders (ASDs) are four times more common in males than in females, but the underlying mechanisms are poorly understood. We characterized sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8 (Chd8+/N2373K) that was first identified in human CHD8 (Asn2373LysfsX2), a strong ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant mice displayed a range of abnormal behaviors during pup, juvenile, and adult stages, including enhanced mother-seeking ultrasonic vocalization, enhanced attachment to reunited mothers, and isolation-induced self-grooming, their female counterparts do not. This behavioral divergence was associated with sexually dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic profiles. Specifically, female mice displayed suppressed baseline neuronal excitation, enhanced inhibitory synaptic transmission and neuronal firing, and increased expression of genes associated with extracellular vesicles and the extracellular matrix. Our results suggest that a human CHD8 mutation leads to sexually dimorphic changes ranging from transcription to behavior in mice.

Lrfn2-Mutant Mice Display Suppressed Synaptic Plasticity and Inhibitory Synapse Development and Abnormal Social Communication and Startle Response.

SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2-/- mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression was detected in both glutamatergic and GABAergic neurons and Lrfn2-/- CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2-/- pups separated from their mothers and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult male Lrfn2-/- mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.SIGNIFICANCE STATEMENT Synaptic adhesion molecules regulate synapse development and function, which govern neural circuit and brain functions. The SALM/LRFN (synaptic adhesion-like molecule/leucine rich repeat and fibronectin type III domain containing) family of synaptic adhesion proteins consists of five known members for which the in vivo functions are largely unknown. Here, we characterized mice lacking SALM1/LRFN2 (SALM1 KO) known to associate with NMDA receptors (NMDARs) and found that these mice showed altered NMDAR-dependent synaptic transmission and plasticity, as expected, but unexpectedly also exhibited suppressed inhibitory synapse development and synaptic transmission. Behaviorally, SALM1 KO pups showed suppressed ultrasonic vocalization upon separation from their mothers and SALM1 KO adults showed enhanced responses to loud acoustic stimuli. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, social communication, and acoustic startle behavior.

Single and multiple sevoflurane exposures during pregnancy and offspring behavior in mice.

BACKGROUND: The second trimester is a period of neurogenesis and neuronal migration, which can be affected by exposure to anesthetics. Studies also suggest that multiple exposures may have a greater impact on neurodevelopment. AIM: We investigated whether in utero single or multiple exposures to anesthetics caused long-term behavior changes. METHODS: Pregnant mice were randomly divided into four groups on gestational day 14 (GD 14). Mice in the Control × 1 group were exposed to 100% oxygen for 150 min. Mice in the Sevo × 1 group were also exposed to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the first 120 min. Mice in the Control × 3 and Sevo × 3 group were identically treated as Control × 1 and Sevo × 1 group for three consecutive days, respectively (GD 14-16). Behavioral tests were performed only with the male offspring at the age of 2-4 months. Synaptic plasticity was also compared by inducing long-term potentiation in acute hippocampal slices. RESULTS: Single or multiple sevoflurane exposures in pregnant mice during the second trimester did not cause long-lasting behavioral consequences or changes in long-term synaptic plasticity of their offspring. CONCLUSION: Our study suggests that neither single nor multiple exposures of mice to sevoflurane during the fetal developmental period induces long-term behavioral dysfunctions or affects long-term synaptic plasticity. Additional studies focusing on early stages of neurodevelopment are necessary to confirm the effects of sevoflurane exposure during pregnancy.

Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period.

Copy number variants and point mutations of NEPH2 (also called KIRREL3) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2-/- mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2-/- mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

Theoretical Calculations on the Feasibility of Microalgal Biofuels: Utilization of Marine Resources Could Help Realizing the Potential of Microalgae.

Microalgae have long been considered as one of most promising feedstocks with better characteristics for biofuels production over conventional energy crops. There have been a wide range of estimations on the feasibility of microalgal biofuels based on various productivity assumptions and data from different scales. The theoretical maximum algal biofuel productivity, however, can be calculated by the amount of solar irradiance and photosynthetic efficiency (PE), assuming other conditions are within the optimal range. Using the actual surface solar irradiance data around the world and PE of algal culture systems, maximum algal biomass and biofuel productivities were calculated, and feasibility of algal biofuel were assessed with the estimation. The results revealed that biofuel production would not easily meet the economic break-even point and may not be sustainable at a large-scale with the current algal biotechnology. Substantial reductions in the production cost, improvements in lipid productivity, recycling of resources, and utilization of non-conventional resources will be necessary for feasible mass production of algal biofuel. Among the emerging technologies, cultivation of microalgae in the ocean shows great potentials to meet the resource requirements and economic feasibility in algal biofuel production by utilizing various marine resources.

Exopolysaccharide microchannels direct bacterial motility and organize multicellular behavior.

The myxobacteria are a family of soil bacteria that form biofilms of complex architecture, aligned multilayered swarms or fruiting body structures that are simple or branched aggregates containing myxospores. Here, we examined the structural role of matrix exopolysaccharide (EPS) in the organization of these surface-dwelling bacterial cells. Using time-lapse light and fluorescence microscopy, as well as transmission electron microscopy and focused ion beam/scanning electron microscopy (FIB/SEM) electron microscopy, we found that Myxococcus xanthus cell organization in biofilms is dependent on the formation of EPS microchannels. Cells are highly organized within the three-dimensional structure of EPS microchannels that are required for cell alignment and advancement on surfaces. Mutants lacking EPS showed a lack of cell orientation and poor colony migration. Purified, cell-free EPS retains a channel-like structure, and can complement EPS- mutant motility defects. In addition, EPS provides the cooperative structure for fruiting body formation in both the simple mounds of M. xanthus and the complex, tree-like structures of Chondromyces crocatus. We furthermore investigated the possibility that EPS impacts community structure as a shared resource facilitating cooperative migration among closely related isolates of M. xanthus.

Enhancing Photon Utilization Efficiency for Astaxanthin Production from Haematococcus lacustris Using a Split-Column Photobioreactor.

A split-column photobioreactor (SC-PBR), consisting of two bubble columns with different sizes, was developed to enhance the photon utilization efficiency in an astaxanthin production process from Haematococcus lacustris. Among the two columns, only the smaller column of SC-PBR was illuminated. Astaxanthin productivities and photon efficiencies of the SC-PBRs were compared with a standard bubble-column PBR (BC-PBR). Astaxanthin productivity of SC-PBR was improved by 28%, and the photon utilization efficiencies were 28-366% higher than the original BC-PBR. The results clearly show that the effective light regime of SC-PBR could enhance the production of astaxanthin.

Seasonal Assessment of Biomass and Fatty Acid Productivity by Tetraselmis sp. in the Ocean Using Semi-Permeable Membrane Photobioreactors.

A green microalga, Tetraselmis sp., was cultivated in the coastal seawater of Young-Heung Island using semi-permeable membrane photobioreactors (SPM-PBRs) in different seasons. The microalgae in the SPM-PBRs were able to grow on nutrients diffused into the PBRs from the surrounding seawater through SPMs. The biomass productivity varied depending on the ion permeabilities of the SPMs and environmental conditions, whereas the quality and quantity of fatty acids were constant. The temperature of seawater had a greater influence than solar radiation did on productivity of Tetraselmis sp. in SPM-PBRs. SPM-PBRs could provide technologies for concurrent algal biomass and fatty acids production, and eutrophication reduction in the ocean.

Development of a floating photobioreactor with internal partitions for efficient utilization of ocean wave into improved mass transfer and algal culture mixing.

Culturing microalgae in the ocean has potentials that may reduce the production cost and provide an option for an economic biofuel production from microalgae. The ocean holds great potentials for mass microalgal cultivation with its high specific heat, mixing energy from waves, and large cultivable area. Suitable photobioreactors (PBRs) that are capable of integrating marine energy into the culture systems need to be developed for the successful ocean cultivation. In this study, prototype floating PBRs were designed and constructed using transparent low-density polyethylene film for microalgal culture in the ocean. To improve the mixing efficiency, various types of internal partitions were introduced within PBRs. Three different types of internal partitions were evaluated for their effects on the mixing efficiency in terms of mass transfer (k(L)a) and mixing time in the PBRs. The partition type with the best mixing efficiency was selected, and the number of partitions was varied from one to three for investigation of its effect on mixing efficiency. When the number of partitions is increased, mass transfer increased in proportion to the number of partitions. However, mixing time was not directly related to the number of partitions. When a green microalga, Tetraselmis sp. was cultivated using PBRs with the selected partition under semi-continuous mode in the ocean, biomass and fatty acid productivities in the PBRs were increased by up to 50 % and 44% at high initial cell density, respectively, compared to non-partitioned ones. The results of internally partitioned PBRs demonstrated potentials for culturing microalgae by efficiently utilizing ocean wave energy into culture mixing in the ocean.

Specific light uptake rates can enhance astaxanthin productivity in Haematococcus lacustris.

Lumostatic operation was applied for efficient astaxanthin production in autotrophic Haematococcus lacustris cultures using 0.4-L bubble column photobioreactors. The lumostatic operation in this study was performed with three different specific light uptake rates (q(e)) based on cell concentration, cell projection area, and fresh weight as one-, two- and three-dimensional characteristics values, respectively. The q(e) value from the cell concentration (q(e1D)) obtained was 13.5 × 10⁻8 µE cell⁻¹ s⁻¹, and the maximum astaxanthin concentration was increased to 150 % compared to that of a control with constant light intensity. The other optimum q e values by cell projection area (q(e2D)) and fresh weight (q( e3D)) were determined to be 195 µE m⁻² s⁻¹ and 10.5 µE g⁻¹ s⁻¹ for astaxanthin production, respectively. The maximum astaxanthin production from the lumostatic cultures using the parameters controlled by cell projection area (2D) and fresh weight (3D) also increased by 36 and 22% over that of the controls, respectively. When comparing the optimal q e values among the three different types, the lumostatic cultures using q(e) based on fresh weight showed the highest astaxanthin productivity (22.8 mg L⁻¹ day⁻¹), which was a higher level than previously reported. The lumostatic operations reported here demonstrated that more efficient and effective astaxanthin production was obtained by H. lacustris than providing a constant light intensity, regardless of which parameter is used to calculate the specific light uptake rate.

Intense pulsed light induced crystallization of a liquid-crystalline polymer semiconductor for efficient production of flexible thin-film transistors.

Here we demonstrated the split-second crystallization of a liquid-crystalline conjugated polymer semiconductor induced by irradiation with intense pulsed white light (IPWL) for the efficient improvement of electrical properties of flexible thin film transistors. A few seconds of IPWL irradiation of poly(didodecylquaterthiophene-alt-didodecylbithiazole) (PQTBTz-C12) thin films generated heat energy through the photo-thermal effect, leading to the crystallization of PQTBTz-C12 and formation of nodule-like nanostructures. The IPWL-induced crystallization of PQTBTz-C12 resulted in a threefold improvement in the field-effect mobility of thin film transistors compared to as-prepared devices. The conformational change of the PQTBTz-C12 chains was found to be strongly related to the irradiation fluence. As a proof-of-concept, the IPWL treatment was successfully applied to the PQTBTz-C12 layer in flexible transistors based on plastic substrates. The performance of these flexible devices was significantly improved after only 0.6 s of IPWL treatment, without deformation of the plastic substrate.

Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning.

Protein ubiquitination has a significant influence on diverse aspects of neuronal development and function. Dorfin, also known as Rnf19a, is a RING finger E3 ubiquitin ligase implicated in amyotrophic lateral sclerosis and Parkinson's disease, but its in vivo functions have not been explored. We report here that Dorfin is a novel binding partner of the excitatory postsynaptic scaffolding protein PSD-95. Dorfin-mutant (Dorfin(-/-)) mice show reduced adult neurogenesis and enhanced long-term potentiation in the hippocampal dentate gyrus, but normal long-term potentiation in the CA1 region. Behaviorally, Dorfin(-/-) mice show impaired contextual fear conditioning, but normal levels of cued fear conditioning, fear extinction, spatial learning and memory, object recognition memory, spatial working memory, and pattern separation. Using a proteomic approach, we also identify a number of proteins whose ubiquitination levels are decreased in the Dorfin(-/-) brain. These results suggest that Dorfin may regulate adult neurogenesis, synaptic plasticity, and contextual fear memory.

Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion.

Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity. SALM3 is a PSD-95-interacting synaptic adhesion molecule known to induce presynaptic differentiation in contacting axons, but little is known about its presynaptic receptors and in vivo functions. Here, we identify an interaction between SALM3 and LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) that requires the mini-exon B splice insert in LAR-RPTPs. In addition, SALM3-dependent presynaptic differentiation requires all three types of LAR-RPTPs. SALM3 mutant (Salm3(-/-)) mice display markedly reduced excitatory synapse number but normal synaptic plasticity in the hippocampal CA1 region. Salm3(-/-) mice exhibit hypoactivity in both novel and familiar environments but perform normally in learning and memory tests administered. These results suggest that SALM3 regulates excitatory synapse development and locomotion behavior.