Exposure to RF-EMF Alters Postsynaptic Structure and Hinders Neurite Outgrowth in Developing Hippocampal Neurons of Early Postnatal Mice

Exposure to radiofrequency electromagnetic fields (RF-EMFs) has increased rapidly in children, but information on the effects of RF-EMF exposure to the central nervous system in children is limited. In this study, pups and dams were exposed to whole-body RF-EMF at 4.0 W/kg specific absorption rate (SAR) for 5 h per day for 4 weeks (from postnatal day (P) 1 to P28). The effects of RF-EMF exposure on neurons were evaluated by using both pups’ hippocampus and primary cultured hippocampal neurons. The total number of dendritic spines showed statistically significant decreases in the dentate gyrus (DG) but was not altered in the cornu ammonis (CA1) in hippocampal neurons. In particular, the number of mushroom-type dendritic spines showed statistically significant decreases in the CA1 and DG. The expression of glutamate receptors was decreased in mushroom-type dendritic spines in the CA1 and DG of hippocampal neurons following RF-EMF exposure. The expression of brain-derived neurotrophic factor (BDNF) in the CA1 and DG was significantly lower statistically in RF-EMF-exposed mice. The number of post-synaptic density protein 95 (PSD95) puncta gradually increased over time but was significantly decreased statistically at days in vitro (DIV) 5, 7, and 9 following RF-EMF exposure. Decreased BDNF expression was restricted to the soma and was not observed in neurites of hippocampal neurons following RF-EMF exposure. The length of neurite outgrowth and number of branches showed statistically significant decreases, but no changes in the soma size of hippocampal neurons were observed. Further, the memory index showed statistically significant decreases in RF-EMF-exposed mice, suggesting that decreased synaptic density following RF-EMF exposure at early developmental stages may affect memory function. Collectively, these data suggest that hindered neuronal outgrowth following RF-EMF exposure may decrease overall synaptic density during early neurite development of hippocampal neurons.     

SREBP-1c Deficiency Affects Hippocampal Micromorphometry and Hippocampus-Dependent Memory Ability in Mice

Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.     

S-Palmitoylation of Synaptic Proteins as a Novel Mechanism Underlying Sex-Dependent Differences in Neuronal Plasticity

Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology, synaptic plasticity, and molecular signaling pathways. Among different processes assuring proper synapse functions are posttranslational modifications, and among them, S-palmitoylation (S-PALM) emerges as a crucial mechanism regulating synaptic integrity. Protein S-PALM is governed by a family of palmitoyl acyltransferases, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase because of its S-PALM action over different synaptic proteins as well as sex steroid receptors. Using the mass spectrometry-based PANIMoni method, we identified sex-dependent differences in the S-PALM of synaptic proteins potentially involved in the regulation of membrane excitability and synaptic transmission as well as in the signaling of proteins involved in the structural plasticity of dendritic spines. To determine a mechanistic source for obtained sex-dependent changes in protein S-PALM, we analyzed synaptoneurosomes isolated from DHHC7-/- (DHHC7KO) female and male mice. Our data showed sex-dependent action of DHHC7 acyltransferase. Furthermore, we revealed that different S-PALM proteins control the same biological processes in male and female synapses.     

Bayesian methods for design and analysis of cost-effectiveness trials in the evaluation of health care technologies

We review the development of Bayesian statistical methods for the design and analysis of randomized controlled trials in the assessment of the cost-effectiveness of health care technologies. We place particular emphasis on the benefits of the Bayesian approach; the implications of skew cost data; the need to model the data appropriately to generate efficient and robust inferences instead of relying on distribution-free methods; the importance of making full use of quantitative and structural prior information to produce realistic inferences; and issues in the determination of sample size. Several new examples are presented to illustrate the methods. We conclude with a discussion of the key areas for future research.     

Overexpression of Tropomyosin Isoform Tpm3.1 Does Not Alter Synaptic Function in Hippocampal Neurons

Tropomyosin (Tpm) has been regarded as the master regulator of actin dynamics. Tpms regulate the binding of the various proteins involved in restructuring actin. The actin cytoskeleton is the predominant cytoskeletal structure in dendritic spines. Its regulation is critical for spine formation and long-term activity-dependent changes in synaptic strength. The Tpm isoform Tpm3.1 is enriched in dendritic spines, but its role in regulating the synapse structure and function is not known. To determine the role of Tpm3.1, we studied the synapse structure and function of cultured hippocampal neurons from transgenic mice overexpressing Tpm3.1. We recorded hippocampal field excitatory postsynaptic potentials (fEPSPs) from brain slices to examine if Tpm3.1 overexpression alters long-term synaptic plasticity. Tpm3.1-overexpressing cultured neurons did not show a significantly altered dendritic spine morphology or synaptic activity. Similarly, we did not observe altered synaptic transmission or plasticity in brain slices. Furthermore, expression of Tpm3.1 at the postsynaptic compartment does not increase the local F-actin levels. The results suggest that although Tpm3.1 localises to dendritic spines in cultured hippocampal neurons, it does not have any apparent impact on dendritic spine morphology or function. This is contrary to the functional role of Tpm3.1 previously observed at the tip of growing neurites, where it increases the F-actin levels and impacts growth cone dynamics.     

Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target

Neurodevelopmental disorders can derive from a complex combination of genetic variation and environmental pressures on key developmental processes. Despite this complex aetiology, and the equally complex array of syndromes and conditions diagnosed under the heading of neurodevelopmental disorder, there are parallels in the neuropathology of these conditions that suggest overlapping mechanisms of cellular injury and dysfunction. Neuronal arborisation is a process of dendrite and axon extension that is essential for the connectivity between neurons that underlies normal brain function. Disrupted arborisation and synapse formation are commonly reported in neurodevelopmental disorders. Here, we summarise the evidence for disrupted neuronal arborisation in these conditions, focusing primarily on the cortex and hippocampus. In addition, we explore the developmentally specific mechanisms by which neuronal arborisation is regulated. Finally, we discuss key regulators of neuronal arborisation that could link to neurodevelopmental disease and the potential for pharmacological modification of arborisation and the formation of synaptic connections that may provide therapeutic benefit in the future.     

FIB-Nanotomography of Particulate Systems—Part I: Particle Shape and Topology of Interfaces

A new 3D-microscopy method, focused ion beam-nanotomography (FIB-nt), has been applied to the statistical particle shape analysis and for topological characterization of granular textures in cement samples. Because of its high resolution (15 nm), FIB-nt reveals precise microstructural information at the submicrometer scale, which cannot be obtained with conventional tomography methods. It is demonstrated that even from complex granular textures with dense agglomerates, it is possible to identify the individual sub-grains. This is the basis for reliable statistical shape analysis. For this purpose, moments of inertia were determined for particles from five different grain size fractions of a given cement, which provides important input data for future modeling of rheology and hydration processes. In addition, FIB-nt was used for topological characterization of the particle–particle interfaces in the dense and fine-grained granular textures. The unique 3D-data obtained with FIB-nt thus open new possibilities for quantitative microstructure analysis and the data can be used as structural input for object-oriented modeling.     

树枝状聚合物的合成和应用

树枝状聚合物具有高度支化的结构和独特的单分散性,使这类聚合物具有特殊的性质和功能,在生物医药、材料改性、工业催化、石油工业等领域有着良好的应用前景。介绍了树枝状聚合物的结构特点、合成方法及应用。     

The Effects of Microstructure and Confinement on the Compressive Fragmentation of an Advanced Ceramic

We investigate the rate‐dependent compressive failure and fragmentation of a hot‐pressed boron carbide, under both uniaxial and confined biaxial compression, using quantitative fragment analysis coupled with quantitative microstructural analysis. Two distinct fragmentation regimes are observed, one of which appears to be more sensitive to the microstructural length scales in the material, while the second is more sensitive to the structural character and boundary conditions of the compressed sample. The first regime, which we refer to as “microstructure‐dependent,” appears to be associated with smaller fragments arising from the coalescence of fractures initiating from graphitic inclusions. This regime appears to become more dominant as the strain rate is increased and as the stress‐state becomes more confined. The second regime generates larger fragments with the resulting fragment size distribution dependent on the specific structural mechanisms that are activated during macroscopic failure (e.g., buckling of local columns developed during the compression). The average fragment size in the latter regime appears to be reasonably predicted by current fragmentation models. This improved understanding of the effects of microstructure and confinement on fragmentation then provides new insights into prior ballistic studies involving boron carbide.     

The Hidden Side of NCAM Family: NCAM2, a Key Cytoskeleton Organization Molecule Regulating Multiple Neural Functions

Although it has been over 20 years since Neural Cell Adhesion Molecule 2 (NCAM2) was identified as the second member of the NCAM family with a high expression in the nervous system, the knowledge of NCAM2 is still eclipsed by NCAM1. The first studies with NCAM2 focused on the olfactory bulb, where this protein has a key role in axonal projection and axonal/dendritic compartmentalization. In contrast to NCAM1, NCAM2’s functions and partners in the brain during development and adulthood have remained largely unknown until not long ago. Recent studies have revealed the importance of NCAM2 in nervous system development. NCAM2 governs neuronal morphogenesis and axodendritic architecture, and controls important neuron-specific processes such as neuronal differentiation, synaptogenesis and memory formation. In the adult brain, NCAM2 is highly expressed in dendritic spines, and it regulates synaptic plasticity and learning processes. NCAM2’s functions are related to its ability to adapt to the external inputs of the cell and to modify the cytoskeleton accordingly. Different studies show that NCAM2 interacts with proteins involved in cytoskeleton stability and proteins that regulate calcium influx, which could also modify the cytoskeleton. In this review, we examine the evidence that points to NCAM2 as a crucial cytoskeleton regulation protein during brain development and adulthood. This key function of NCAM2 may offer promising new therapeutic approaches for the treatment of neurodevelopmental diseases and neurodegenerative disorders.     

On the use of biomarkers for environmental health research

This article discusses the growing interest in the use of biomarker data in environmental health research and considers some of the challenging statistical issues that arise. We specify a modeling framework that links environmental exposure, biomarkers and outcome, and discuss in conceptual terms how such a formulation could be used to inform dose response modeling for the purpose of quantitative risk assessment. We then analyse some biomarker data from a case-control study designed to elucidate the mechanisms of smoking induced lung cancer. Because of sample size limitations, we use a likelihood-based analysis which subsumes both cohort and case-control designs as special cases. Our analysis allows us to 1) investigate the extent to which the markers explain the pathway from exposure to outcome; 2) quantify the degree to which biomarker data can improve on predicting outcome over and above exposure; and 3) estimate the association among multiple markers.     

样品粒度对差热分析影响的研究

研究了差热定量分析面积法的准确性和不同物料样品粒度对定性差热分析的影响。研究结果表明：对不同样品，粒度在20－250目范围时，昨用差热分析作定性分析，样品粒度对分析结果基本无影响，但用差热分析作定量分析时，要控制合理的样品粒度。     

Guanidinylated dendritic molecular transporters: prospective drug delivery systems and application in cell transfection

In the present review the crucial role of the guanidinium functional group in facilitating the transport of dendritic polymers through liposomal and cell membranes is discussed, along with other structural features of guanidinylated dendritic polymers that fine-tune their transport properties, and even determine their subcellular destinations. In this context, an ideal dendritic molecular transporter would need to possess a dendritic scaffold of the appropriate size and degree of guanidinylation, flexibility of the guanidinium moiety, and should exhibit a proper balance between hydrophilic and hydrophobic moieties located on the dendritic surface. All of the above are illustrated through selected paradigms from the relevant literature, which give a valuable insight into forging successful dendritic delivery systems for both drugs and genes. The main challenge for the future focus of the field is identified as the determination of the key structural and functional characteristics that will enhance cell internalisation, and secure localisation in specific subcellular organelles.     

PSA Depletion Induces the Differentiation of Immature Neurons in the Piriform Cortex of Adult Mice

Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.     

Microstructure of Gas Diffusion Layers for PEM Fuel Cells

The gas diffusion layer (GDL) is a critical component of a proton exchange membrane fuel cell, and can play a key role in fuel cell performance. In order to design reliable and durable fuel cells, knowledge of the GDL microstructure is necessary. Currently, characterization of GDLs is generally based on porosity measurements to obtain a pore size distribution. However, the pore size distribution in GDLs may not be the only factor that affects the fuel cell performance. Additional microstructural characterization of GDLs manufactured by three different vendors (Toray, SGL, and Freudenberg) has been investigated. In addition to the pore size distribution, other statistical information of GDL microstructure including size, shape, orientation, and distribution of pores have been characterized and compared. Among these GDLs, the Freudenberg sample was found to have the smallest pore size and orientation analysis indicated that the pores were randomly distributed. Pore roundness was the lowest and pore clustering was highest in Toray sample. The effect of threshold setting on pore size data was also studied and found to have negligible influence on the calculated distributions. The microstructures of the GDLs were reconstructed in three‐dimension using computer simulations and good agreement with the two‐dimensional image analysis data was observed. The present work opens new opportunities for experimentalists and modelers in the area of fuel cell research to take into account the statistical characteristics of GDL microstructure.     

PR-30型高分子破乳剂的研究

本文采用Mickeal加成和酰胺化缩合反应,合成了树枝形聚合物-聚酰胺-胺(PAMAM),实验配制了PR-30型高分子破乳剂。讨论了反应温度、反应时间对破乳效果的影响,并采用模拟原油乳状液,对复配后样品的破乳效果进行了初步评价。     

A green process for the synthesis of controllable mesoporous silica materials

The synthesis, characterization, and application of mesoporous silicas have attracted a lot of attention for over two decades, which stems from their fascinating structures, formation mechanisms and prospects of their applications. Various methods have been developed for the synthesis of these silicas with a tunable pore diameter and a narrow pore size distribution. In this paper, mesoporous silica materials with controllable pore diameters (3-9 nm), narrow pore size distributions, high surface area (>700 m² g⁻¹) and pore volume (>1 cm³ g⁻¹) were prepared by a green template, amphiphilic dendritic polyamidoamine. The resulting silica materials were characterized by ¹H, ¹³C NMR spectroscopy; thermogravimetic analysis; nitrogen adsorption; transmission electron microscope. It was shown that the template could be completely removed and recycled from the silica in an environmentally friendly way by means of a simple water extraction. Furthermore, it was shown that the pore diameter of these materials could be controlled by dendritic polyamidoamine with different generations and functional groups. Meanwhile, the porous framework showed strong thermal stability. Thus, a new environmentally friendly pathway for the controllable synthesis of this fascinating silicas has been proposed.     

Off lattice Monte Carlo simulations of AB hybrid dendritic star copolymers

The conformational properties of Hybrid Dendritic Star copolymers (HDS) which combine the characteristics of dendrimers with those of flexible polymers are studied, for the first time, by means of Off Lattice Monte Carlo simulations. Using the efficient Pivot algorithm we calculate the asphericity and the acylindricity of the whole molecule for various solvent conditions and different characteristics of dendritic and star chains. Moreover, the effects of the number and the length of star branches on the conformation of the dendritic part are also studied. By considering the HDS copolymers as ‘hairy spheres’ we have calculated the star monomer distribution profiles. The shapes of the profiles are compared with previous Monte Carlo results.     

Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury

Endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI). We have previously shown that melatonin (MT) plus exercise (Ex) had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups. These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.