Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Experimental models of high-risk bowel anastomosis in rats:A systematic review

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Classic mechanisms and experimental models for the anti-inflammatory effect of traditional Chinese medicine

Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.

Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

BACKGROUND： Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy （AION）. OBJECTIVE ： To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography （FFA）, optical coherence tomography （OCT）, flash visual evoked potential （F-VEP）, and histopathologically confirm its reliability. DESIGN： A randomized control tria SETTINGS ： Department of Ophthalmology, Xi＇an Fourth Hospital; Xi＇an Institute of Ocular Fundus Diseases MATERIALS ： The experiments were carried out in the research room of Xi＇an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK （Military）2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group （n =5）, laser group （n =5）, hematoporphyrin derivative （HPD） group and AION group （n =15）, each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS： In the AION group, the rats were injected with HPD （10 mg/kg） via caudal vein, and then the optic discs were exposed to krypton red （647 nm, 80 mV） for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red （647 rim, 80 mV） for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD （10 mg/kg） via caudal vein; Those in the blank control group were untouched. （1） Visual electrophysiological test： The F-VEP was used to evaluate the function of visual nerve. （2） FFA： After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution （1 mL/kg） was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. （3） After mydriasis and anesthesia as describe above, the rats were examined with OCT. （4） Histological observation： After hematoxylin and eosin （HE） staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES： The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS： Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. （1） Changes in fundus： In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. （2） FFA results： In the AION group, early ＂low fluorescence＂, middle and late ＂high fluorescence＂ were observed in upper optic disc 1 day after model establishment, and there was ＂low fluorescence＂ at 6 days, and the low fluorescence could be observed all the time at 23 days. （3） Visual electrophysiological changes： In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [（71.65±8.81）, （57.58±8.38） ms, t =3.148, P =0.012], and decreased wave amplitude [（4.77±1.90）, （10.06±3.66） μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. （4） OCT results： In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. （5） Histopathological results： At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION ： The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation （647 nm） at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.

Evaluating the Amount of Erodability and Sedimentation by Comparing Sediment Weight Model and PSIAC Experimental Model (Case Study: Lali Water Catchment, Khuzestan, Iran)

The upstream water catchments are the main source providing sediments in rivers and sedimentary basins. The balance between the erosion phenomenon and the amount of sediment entering into the basin relies on the geometrical specifications and the morphology of the river along the water catchment direction and the amount and type of the sediments. The sedimentary feed of rivers and basins are changed for the sake of natural factors or human disturbances. The river and basin react against this change in that their shape, morphology, plan and profile get changed due to the increase or decrease of the input sediment into the basin. It is essential to know the sediment amount produced by erodability and sedimentation of upstream basins and effects of projects and also to evaluate the amount of sedimentary load in base studies, civil projects, optimizing rivers and dam construction studies specially calculating the amount of sediment amount entering into the dams’ reservoirs in order to take engineering decisions and related alternatives. Sediment Weight Model and PSIAC Experimental Model are recognized as two common methods calculating the amount of the produced sediment caused by erosion applied in this research. Holistically, these methods have been used and compared. Although the results are almost close to one another, more sediment load has been produced in PSIAC method. As more affective parameters are used to cause erosion and produce sediment in PSIAC experimental model, it is recommended to refer to the results of this method because they are closer to reality.

Human prostate cancer heterotransplants： a review on this experimental model

A common model used for preclinical research was in vitro human tumor cell culture. An alternative model was the direct implantation of a unique patient＇s tumor biopsy specimens into immunodeficient host mice. Published data from PubMed （http：//www.ncbi.nlm.nih.gov） and Current Contents Connect databases （http：//thomsonreuters.com/ products_services/science/science_roducts/a-z/current_contents_connect） were reviewed. Prostate cancer （PCa） heterotransplantation was evaluated using histopathology, morphology, cell differentiation, DNA content, tumor marker expression, metastases, tumor kinetics, tumor take rate and tumor vasculature in the first tumor heterotransplant. The heterotransplanted tumor retained the biological properties of the original tumor, such as morphology, degree of differentiation, pathology, secretory activity, expression of tumor markers and human vasculature. Human PCa heterotransplants have considerable experimental advantages over cell culture following xenotransplantation.

Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction

Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN®, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN® 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN® significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p < 0,05), reflex control of SSNA (+29.4%, p < 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

A new experimental model to study healing process of metaphyseal fracture

Background There are few researches for the healing of metaphyseal fractures; moreover,the animal models to study the metaphyseal fractures are usually made by the oscillating saw osteotomy without reliable fixation,which is not in accordance with our current clinical practice.In this study,we established a new model to observe the healing process of metaphyseal fractures.Methods Eighteen New Zealand rabbits were used in the study.The fracture model was created by splitting the medial tibial plateau in rabbits,then reset,and fixed with compression screws.At 1,2,3,4,6,and 8 weeks postoperatively,the tibial specimens were collected; firstly,a general observation and an X-ray examination of the specimens was done,and then they were embedded in methylmethacrylate and cut into sections with hard tissue slicer.The sections were stained with Giemsa reagent and examined under light microscopy.Results There was no fracture displacement in the tibial specimens of all time points,except for one showing a collapse.No external callus formation could be observed by X-ray and general examination.After 1 week of the operation,the fracture gap was filled by mesenchymal tissue; 2 weeks postoperatively,a large number of woven bones were formed; from the third week onwards,the woven bone began to turn into lamellar bone,and new trabecular structure began to form.In all of the slices,no obvious chondrocytes formed in fracture areas; thus,there was no endochondral ossification.Conclusions This model was an ideal fracture animal model and suitable for the study of metaphyseal fracture healing.The X-ray and histological images demonstrated that metaphyseal fracture healing was a process of direct bone healing through intramembranous bone formation under the conditions of minor trauma,good reduction,and firm fixation.

Experimental modeling of polymer latex spray coating for producing controlled-release urea

Spray coating of polymer latex onto fertilizer particles in a fiuidized bed for producing controlled-release urea is an environment friendly technology as it does not need any toxic organic solvent. Since the spray coating process in a fluidized bed occurs in the presence of particle collisions, the coating of the particles is random, intermittent and multiple, thus making it difficult to investigate the film formation process. In this paper, an experimental model apparatus was designed and used to investigate the effects of the key factors in the spray coating process. This apparatus reasonably simplified the complex process to avoid particle collisions and randomness in the coating. The intermittent coating in the fluidized bed was modeled by periodic coating and dewatering in the experimental apparatus. A large area film was obtained, and the film permeability was measured. The effects of atomizing gas flow rate, spray rate of latex, solid content of latex and gas temperature on film structure and film permeability were investigated. It was found that water transfer played a dominant role in the spray coating process.

Experimental models of endocrine responsive breast cancer: strengths, limitations, and use

Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.

CFD/CSD-based flutter prediction method for experimental models in a transonic wind tunnel with porous wall

To predict the flutter dynamic pressure of a wind tunnel model before flutter test,an accurate Computational Fluid Dynamics/Computational Structural Dynamics(CFD/CSD)-based flutter prediction method is proposed under the conditions of a 2.4 m×2.4 m transonic wind tunnel with porous wall.From the CFD simulations of the flows through an inclined hole of this wind tunnel,the Nambu's linear porous wall model between the flow rate and the differential pressure is extended to the porous wall with inclined holes,so that the porous wall can be conveniently modeled as a boundary condition.According to the flutter testing approach for the current wind tunnel,the steady CFD calculation is conducted to achieve the required inlet Mach number.A timedomain CFD/CSD method is then employed to evaluate the structural response of the experimental model,and the critical flutter point is obtained by increasing the dynamic pressure step by step at a fixed Mach number.The present method is applied to the flutter calculations for a vertical tail model and an aircraft model tested in the current transonic wind tunnel.For both models,the computed flutter characteristics agree well with the experimental results.

Experimental models of endocrine responsive breast cancer: strengths, limitations, and use

Breast cancers characterized by expression of estrogen receptor-alpha(ER;ESR1)represent approximately 70%of all new cases and comprise the largest molecular subtype of this disease.Despite this high prevalence,the number of adequate experimental models of ER+breast cancer is relatively limited.Nonetheless,these models have proved very useful in advancing understanding of how cells respond to and resist endocrine therapies,and how the ER acts as a transcription factor to regulate cell fate signaling.We discuss the primary experimental models of ER+breast cancer including 2D and 3D cultures of established cell lines,cell line-and patient-derived xenografts,and chemically induced rodent models,with a consideration of their respective general strengths and limitations.What can and cannot be learned easily from these models is also discussed,and some observations on how these models may be used more effectively are provided.Overall,despite their limitations,the panel of models currently available has enabled major advances in the field,and these models remain central to the ability to study mechanisms of therapy action and resistance and for hypothesis testing that would otherwise be intractable or unethical in human subjects.

Animal models for anti-neutrophil cytoplasmic antibody-associated vasculitis:Are current models good enough?

Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.

Experimental nerve transfer model in the neonatal rat

Clinically,peripheral nerve reconstructions in neonates are most frequently applied in brachial plexus birth injuries.Most surgical concepts,however,have investigated nerve reconstructions in adult animal models.The immature neuromuscular system reacts differently to the effects of nerve lesion and surgery and is poorly investigated due to the lack of reliable experimental models.Here,we describe an experimental forelimb model in the neonatal rat,to study these effects on both the peripheral and central nervous systems.Within 24 hours after birth,three groups were prepared:In the nerve transfer group,a lesion of the musculocutaneous nerve was reconstructed by selectively transferring the ulnar nerve.In the negative control group,the musculocutaneous nerve was divided and not reconstructed and in the positive control group,a sham surgery was performed.The animal's ability to adapt to nerve lesions and progressive improvement over time were depict by the Bertelli test,which observes the development of grooming.Twelve weeks postoperatively,animals were fully matured and the nerve transfer successfully reinnervated their target muscles,which was indicated by muscle force,muscle weight,and cross sectional area evaluation.On the contrary,no spontaneous regeneration was found in the negative control group.In the positive control group,reference values were established.Retrograde labeling indicated that the motoneuron pool of the ulnar nerve was reduced following nerve transfer.Due to this post-axotomy motoneuron death,a diminished amount of motoneurons reinnervated the biceps muscle in the nerve transfer group,when compared to the native motoneuron pool of the musculocutaneous nerve.These findings indicate that the immature neuromuscular system behaves profoundly different than similar lesions in adult rats and explains reduced muscle force.Ultimately,pathophysiologic adaptations are inevitable.The maturing neuromuscular system,however,utilizes neonatal capacity of regeneration and seizes a variety of compensation mechanism to restore a functional extremity.The above described neonatal rat model demonstrates a constant anatomy,suitable for nerve transfers and allows all standard neuromuscular analyses.Hence,detailed investigations on the pathophysiological changes and subsequent effects of trauma on the various levels within the neuromuscular system as well as neural reorganization of the neonatal rat may be elucidated.This study was approved by the Ethics Committee of the Medical University of Vienna and the Austrian Ministry for Research and Science(BMWF-66.009/0187-WF/V/3 b/2015)on March 20,2015.

Experimental Observation of the Ground-State Geometric Phase of Three-Spin XY Model

The geometric phase has become a fundamental concept in many fields of physics since it was revealed. Recently, the study of the geometric phase has attracted considerable attention in the context of quantum phase transition, where the ground state properties of the system experience a dramatic change induced by a variation of an external parameter. In this work, we experimentally measure the ground-state geometric phase of the three-spin XY model by utilizing the nuclear magnetic resonance technique. The experimental results indicate that the geometric phase could be used as a fingerprint of the ground-state quantum phase transition of many-body systems.

How do stream processes affect hazard exposure on alluvial fans? Insights from an experimental study

Alluvial fans are among the most privileged settlement areas in many mountain regions. These landforms are particularly dynamic being episodically affected by distributary processes generated by extreme flood events. Addressing risk assessment entails determining hazard exposure and unravelling how it might be related to process loading and to process dynamics once the flow becomes unconfined on the surface of alluvial fans. By following a ‘similarity of process concept’, rather than by attempting to scale a real-world prototype, we performed a set of 72 experimental runs on an alluvial fan model. Thereby, we considered two model layouts, one without a guiding channel and featuring a convex shape and the other one with a guiding channel, a bridge, and inclined but planar overland flow areas as to mirror an anthropic environment. Process magnitude and intensity parameters were systematically varied, and the associated biphasic distributary processes video recorded. For each experiment, the exposure was detected by mapping the exposed area in a GIS, thereby discerning between areas exposed to biphasic flows and the associated depositional phenomena or to the liquid flow phase only. Our results reveal that total event volume, sediment availability and stream power in the feeding channel, as well as depositional effects, avulsion, and channelization on the alluvial fan concur to determine the overall exposure. Stream process loading alone, even when rigorously defined in terms of its characterizing parameters, is not sufficient to exhaustively determine exposure. Hence, further developing reliable biphasic simulation models for hazard assessment on settled alluvial fans is pivotal.