Morphologic and functional changes in the unilateral 6-hydroxydopamine lesion rat model for Parkinson’s disease discerned with μSPECT and quantitative MRI

Object

In the present study, we aimed to evaluate the impact of neurodegeneration of the nigrostriatal tract in a rodent model of Parkinson’s disease on the different MR contrasts (T₂, T₁, CBF and CBV) measured in the striatum.

Material and methods

Animals were injected with 6-hydroxydopamine (6OHDA) in the substantia nigra resulting in massive loss of nigrostriatal neurons and hence dopamine depletion in the ipsilateral striatum. Using 7T MRI imaging, we have quantified T₂, T₁, CBF and CBV in the striata of 6OHDA and control rats. To validate the lesion size, behavioral testing, dopamine transporter μSPECT and tyrosine hydroxylase staining were performed.

Results

No significant differences were demonstrated in the absolute MRI values between 6OHDA animals and controls; however, 6OHDA animals showed significant striatal asymmetry for all MRI parameters in contrast to controls.

Conclusions

These PD-related asymmetry ratios might be the result of counteracting changes in both intact and affected striatum and allowed us to diagnose PD lesions. As lateralization is known to occur also in PD patients and might be expected in transgenic PD models as well, we propose that MR-derived asymmetry ratios in the striatum might be a useful tool for in vivo phenotyping of animal models of PD.     

高密度电子封装器件的温度分布研究

系统封装(System In Packaging)是电子封装工艺的前沿技术。为了研究这种高密度电子封装器件的热特性,寻求提高散热速率的途径,开发了一个SIP典型器件的传热模型,模拟了器件的热传递过程和温度分布状况,探讨了各种设计参数和物性参数对温度场的影响,为进一步改善器件的热性能提供了理论依据。     

Bioluminescent Optogenetics: A Novel Experimental Therapy to Promote Axon Regeneration after Peripheral Nerve Injury

Functional recovery after peripheral nerve injury (PNI) is poor, mainly due to the slow and incomplete regeneration of injured axons. Experimental therapies that increase the excitability of the injured axons have proven remarkably successful in promoting regeneration, but their clinical applicability has been limited. Bioluminescent optogenetics (BL-OG) uses luminopsins, fusion proteins of light-generating luciferase and light-sensing ion channels that could be used to increase neuronal excitability if exposed to a suitable substrate. Excitatory luminopsins were expressed in motoneurons of transgenic mice and in wildtype mice transduced with adeno-associated viral vectors. Intraperitoneal administration of coelenterazine (CTZ), a known luciferase substrate, generated intense bioluminescence in peripheral axons. This bioluminescence increased motoneuron excitability. A single administration of CTZ immediately after sciatic nerve transection and repair markedly enhanced motor axon regeneration. Compound muscle action potentials were 3–4 times larger than controls by 4 weeks after injury. The results observed with transgenic mice were comparable to those of mice in which the luminopsin was expressed using viral vectors. Significantly more motoneurons had successfully reinnervated muscle targets four weeks after nerve injury in BL-OG treated mice than in controls. Bioluminescent optogenetics is a promising therapeutic approach to enhancing axon regeneration after PNI.     

Nanopaper membranes from chitin–protein composite nanofibers—structure and mechanical properties

Chitin nanofibers may be of interest as a component for nanocomposites. Composite nanofibers are therefore isolated from crab shells in order to characterize structure and analyze property potential. The mechanical properties of the porous nanopaper structures are much superior to regenerated chitin membranes. The nanofiber filtration‐processing route is much more environmentally friendly than for regenerated chitin. Minerals and extractives are removed using HCl and ethanol, respectively, followed by mild NaOH treatment and mechanical homogenization to maintain chitin–protein structure in the nanofibers produced. Atomic force microscope (AFM) and scanning transmission electron microscope (STEM) reveal the structure of chitin–protein composite nanofibers. The presence of protein is confirmed by colorimetric method. Porous nanopaper membranes are prepared by simple filtration in such a way that different nanofiber volume fractions are obtained: 43%, 52%, 68%, and 78%. Moisture sorption isotherms, structural properties, and mechanical properties of membranes are measured and analyzed. The current material is environmentally friendly, the techniques employed for both individualization and membrane preparation are simple and green, and the results are of interest for development of nanomaterials and biocomposites. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40121.     

A new ternary phase in the system CaO–Al2O3–Cr2O3: Crystal structure and thermal expansion of CaAl2Cr2O7

Polycrystalline material of a novel phase in the system CaO–Al₂O₃–Cr₂O₃ has been obtained by solid-state reactions. Chemical analysis indicated the composition CaAl₂Cr₂O₇. Single-crystal growth of the new compound using borax as a mineralizer was successful. Diffraction experiments at ambient conditions on a crystal with composition CaAl_2.13Cr_1.87O₇ yielded the following basic crystallographic data: space group P 3, a = 7.7690(5) Å, c = 7.6463(5) Å, V = 399.68(6) ų, Z = 3. Structure determination and subsequent least-squares refinements resulted in a residual of R(|F|) = 2.3% for 1440 independent observed reflections and 113 parameters. To the best of our knowledge, the structure of CaAl_2.13Cr_1.87O₇ or CaAl₂Cr₂O₇ represents a new structure type. It belongs to the group of double layer structures where individual double layers contain octahedrally and tetrahedrally coordinated cation positions. Linkage between neighboring sheet packages is provided by additional calcium cations. Furthermore, thermal expansion has been studied in the interval between 29 and 790°C using in situ high-temperature single-crystal diffraction. No indications for a structural phase transition were observed. From the evolution of the lattice parameters the thermal expansion tensor has been obtained. A pronounced anisotropy is evident. The response of structural building units to variable temperature has been discussed.     

Multiparameter Evaluation of the Platelet-Inhibitory Effects of Tyrosine Kinase Inhibitors Used for Cancer Treatment

Current antiplatelet drugs for the treatment of arterial thrombosis often coincide with increased bleeding risk. Several tyrosine kinase inhibitors (TKIs) for cancer treatment inhibit platelet function, with minor reported bleeding symptoms. The aim of this study was to compare the antiplatelet properties of eight TKIs to explore their possible repurposing as antiplatelet drugs. Samples of whole blood, platelet-rich plasma (PRP), or isolated platelets from healthy donors were treated with TKI or the vehicle. Measurements of platelet aggregation, activation, intracellular calcium mobilization, and whole-blood thrombus formation under flow were performed. Dasatinib and sunitinib dose-dependently reduced collagen-induced aggregation in PRP and washed platelets; pazopanib, cabozantinib, and vatalanib inhibited this response in washed platelets only; and fostamatinib, axitinib, and lapatinib showed no/limited effects. Fostamatinib reduced thrombus formation by approximately 50% on collagen and other substrates. Pazopanib, sunitinib, dasatinib, axitinib, and vatalanib mildly reduced thrombus formation on collagen by 10–50%. Intracellular calcium responses in isolated platelets were inhibited by dasatinib (>90%), fostamatinib (57%), sunitinib (77%), and pazopanib (82%). Upon glycoprotein-VI receptor stimulation, fostamatinib, cabozantinib, and vatalanib decreased highly activated platelet populations by approximately 15%, while increasing resting populations by 39%. In conclusion, the TKIs with the highest affinities for platelet-expressed molecular targets most strongly inhibited platelet functions. Dasatinib, fostamatinib, sunitinib, and pazopanib interfered in early collagen receptor-induced molecular-signaling compared with cabozantinib and vatalanib. Fostamatinib, sunitinib, pazopanib, and vatalanib may be promising for future evaluation as antiplatelet drugs.     

The Impact of Gut Microbiota-Derived Metabolites in Autism Spectrum Disorders

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome–host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.     

Accelerated weathering properties of compatibilized composites made from recycled HDPE and nonmetallic printed circuit board waste

The main aim of this work is to examine the influence of the contents of nonmetallic printed circuit board (PCB) waste component on the photodegradation of recycled high‐density polyethylene (rHDPE) composites. The properties tested were chemical changes, flexural properties, color stability, water absorption, leaching properties, and crystallinity changes of the composites after exposure to 2,000 h of accelerated weathering. Surface degradation for composites with nonmetallic PCB was less compared to unfilled rHDPE mainly because glass fibers covered almost the whole surface of specimens, acting as a protective layer, thus, slowing down the photodegradation reaction. Incorporation of compatibilizer in rHDPE/PCB composites had played an important role in resisting degradation due to UV exposure. All the composite samples became lighter in the early stages of weathering exposure; however, compatibilized composites showed less lightening and reduction on strength and modulus. Carbonyl index increases with exposure time indicating that the oxidation reaction continuously occurred during the aging process. Incorporation of compatibilizer had successfully reduced the water absorption uptake by the composites and effectively delayed some degradation properties of weathering. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43110.     

PEPT study of particle cycle and residence time distributions in a Wurster fluid bed

Particle cycle and residence time distributions are critical factors in determining the coating quality in the Wurster process. Positron emission particle tracking experiments are performed to determine the cycle and residence times of particles in different regions of a Wurster fluid bed. The results show that particles tend to recirculate in and sneak out below from the Wurster tube. The experiments also show that a larger batch size leads to a shorter cycle time and a narrower cycle time distribution (CTD). It is possible to avoid recirculations and obtain a shorter cycle time and a narrower CTD by selecting the operating conditions appropriately or via equipment design. Experiments using binary mixtures of particles with a diameter ratio of 1.5 show that large particles have a longer cycle time than small particles and that the cycle time is shorter for mixtures with approximately equal amounts of small and large particles. © 2014 American Institute of Chemical Engineers AIChE J, 61: 756–768, 2015