Influence of Species Differences on the Neuropathology of Transgenic Huntington's Disease Animal Models

Transgenic animal models have revealed much about the pathogenesis of age-dependent neurodegenerative diseases and proved to be a useful tool for uncovering therapeutic targets. Huntington＇s disease is a well-characterized neurodegenerative disorder that is caused by expansion of a CAG repeat, which results in expansion of a polyglutamine tract in the N-terminal region of huntingtin （HTT）. Similar CAG/glutamine expansions are also found to cause eight other neurodegenerative diseases that affect distinct brain regions in an age- dependent manner. Identification of this CAG/glutamine expansion has led to the generation of a variety of transgenic animal models. Of these different animal models, transgenic mice have been investigated extensively, and they show similar neuropathology and phenotypes as seen in their respective diseases. The common pathological hallmark of age-dependent neurodegeneration is the formation of aggregates or inclusions consisting of misfolded proteins in the affected brain regions; however, overt or striking neurodegeneration and apoptosis have not been reported in most transgenic mouse models for age-dependent diseases, including HD. By comparing the neuropathology of transgenic HD mouse, pig, and monkey models, we found that mutant HTT is more toxic to larger animals than mice, and larger animals also show neuropathology that has not been uncovered by transgenic mouse models. This review will discuss the importance of transgenic large animal models for analyzing the treatments. pathogenesis of neurodegenerative diseases and developing effective

Morphological change and migration of revegetated dunes in the Ketu Sandy Land of the Qinghai Lake,China

Alpine revegetated dunes have been barely researched in terms of morphological change and migration within its regional aeolian environments. To reveal the sand-fixing and land-reforming mechanisms of artificial vegetation, we observed the morphology and migration of four dunes with four revegetated types(Hippophae rhamnoides Linn., Salix cheilophila Schneid., Populus simonii Carr., and Artemisia desertorum Spreng.) using unpiloted aerial vehicle images and GPS(global positioning system) mapping in 2009 and 2018. Spatial analysis of GIS(geographic information system) revealed that the revegetated dunes exhibited a steady progression from barchan dune shapes to dome or ribbons shapes mainly through knap planation, wing amplification, and slope symmetrization. Generally, conditions of northern aspects, smaller slope degree, and larger altitude of unvegetated dunes would suffer more serious wind erosion. The southward movement of dune wings with a migration speed of 2.0–5.0 m/a and the alternating motion of sand ridges in eastwestern directions led greater stability in revegetated dunes. The moving distances of revegetated dunes remarkably changed in patterns of quadratic or linear function with depositional depth. Compared with unvegetated dunes, the near-surface wind velocity of revegetated dunes decreased by 20%–30%, which led to heavy accumulation in low-flat dunes and erosion in high-steep dunes, but all vegetation species produced obvious sand-fixing benefits(100%–450% and 3%–140% in the lower and higher dune scales of revegetated dunes, respectively) with decreasing sand transport rates and increasing coverages. In practice, the four vegetation species effectively anchored mobile dunes by adapting to regional aeolian environment. However, future revegetation efforts should consider optimizing dune morphology by utilizing H. rhamnoides as a pioneer plant, S. cheilophila and P.microphylla in windward and northward dune positions, and A. desertorum in a sand accumulative southward position. Also, we should adjust afforestation structure and replant some shrub or herbs in the higher revegetated dunes to prevent fixed dune activation and southward expansion.

In vivo mouse models to study bile acid synthesis and signaling

The synthesis of bile acids(BAs)is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450(CYP)and other enzymes.Maintaining the integrity of these pathways is crucial for normal physiological function in mammals,encompassing hepatic and neurological processes.Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor(FXR)signaling and metabolic homeostasis.By creating mouse knockout(KO)models,researchers can manipulate deficiencies in genes involved in BA synthesis,which can be used to study human diseases with BA dysregulation.These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis.Furthermore,KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling.Notably,alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies.This review summarizes several mouse KO models used to study BA synthesis and related human diseases,including mice deficient in Cyp7a1,Cyp27a1,Cyp7a1/Cyp27a1,Cyp8b1,Cyp7b1,Cyp2c70,Cyp2a12,and Cyp2c70/Cyp2a12,as well as germ-free mice.

Plasma-Assisted ALD of an Al_2O_3 Permeation Barrier Layer on Plastic

Atomic layer deposition （ALD） technique is used in the preparation of organic/inorganic layers, which requires uniform surfaces with their thickness down to several nanometers. For film with such thickness, the growth mode defined as the arrangement of clusters on the surface during the growth is of significance. In this work, Al2O3 thin film was deposited on various interfacial species of pre-treated polyethylene terephthalate （PET, 12 μm） by plasma assisted atomic layer deposition （PA-ALD）, where trimethyl aluminium was used as the Al precursor and O2 as the oxygen source. The interracial species, -NH3, -OH, and -COOH as well as SiCHO （derived from monomer of HMDSO plasma）, were grafted previously by plasma and chemical treatments. The growth mode of PA-ALD Al2O3 was then investigated in detail by combining results from in-situ diagnosis of spectroscopic ellipsometry （SE） and ex-situ characterization of as-deposited layers from the morphologies scanned by atomic force microscopy （AFM）. In addition, the oxygen transmission rates （OTR） of the original and treated plastic films were measured. The possible reasons for the dependence of the OTR values on the surface species were explored.

Comparison of different phosphate species adsorption by ferric and alum water treatment residuals

As safe byproducts of drinking water treatment processes,ferric and alum water treatment residuals（FARs） have the potential to be new phosphate（P） immobilization materials.In this study,batch experiments were conducted to investigate and compare the adsorption characteristics of three P species by FARs.The results showed that the kinetic processes of different P species＇ adsorption by FARs could be described by a pseudo second-order model.The ranking list of the initial adsorption rates with respect to different phosphates was pyrophosphate,phytate,orthophosphate,hexametaphosphate and glycerophosphate.Of the six models considered,the two-site Langmuir model most effectively described the adsorption characteristics of the various P species.Upon fitting the results,the maximum adsorption capacities were determined to be 40.24 mg/g for phytate,18.04 mg/g for pyrophosphate,17.14 mg/g for orthophosphate,15.86 mg/g for hexametaphosphate and 10.81 mg/g for glycerophosphate.In addition,the adsorption processes of the different P species were spontaneous endothermic processes and were favored at lower pH values.The pH dependency was found to be especially true for orthophosphate,where the adsorption capacity decreased by 1.22 mg/g with an increase in pH from 5 to 9.Fractionation of the adsorbed P species from the FARs demonstrated that Al-P and Fe-P were the dominating forms,constituting approximately 80%-90% of the total P fractions,which indicated that the adsorbed P species had a low leaching risk and could stably exist in the FARs.Therefore,the FARs could be effective in controlling pollution in water caused by different P species.

SUPEROXIDE RADICAL SCAVENGING AND CYTOTOXIC EFFECTS OF DIFFERENT MARINE SPECIES FROM TURKEY'S COASTS

In this study,acetone extracts of thirteen different species distributed in Turkey Coasts including tunicates,sea anemones,sponges and corals were investigated for their superoxide(SO)radical scavenging and cytotoxic activities.VWhile SO radical scavenging activity was tested using alkaline DMSO method,cytotoxic activity was tested by MTT assay against Hep-2 cancer cell line.As a result of bioactivity studies,Paramuricea clavata extract showed

In vivo degradation and endothelialization of an iron bioresorbable scaffold

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds(BRSs).In particular,it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments;otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial.Herein,we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold(IBS)based on optical coherence tomography(OCT)images;this approach was confirmed to be consistent with the present weight-loss measurements,which is,however,a destructive approach.The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent.The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience,which has been widely used in clinic.The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model;and our well-designed ultrathin stent exhibited less individual variation.We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models.The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model.The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.