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suicide transport blockade of motor neuron survival generates a focal graded injury and functional deficit

Neural Regeneration Research 2021年第7期16卷 1281-1287页

作者： allison s.liang Joanna E.Pagano Christopher A.Chrzan Randall D.McKinnon Department of Neurosurgery Rutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA Member The Cancer Institute of New JerseyNew BrunswickNJUSA

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small *** axonal transport of a pro-apoptotic phosphatidylinosotol 3'-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug *** neuron loss was detected by choline acetyltransferase(ChAT) immunostaining and with a transgenic thy1-eGFP *** short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus *** quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 *** effects were observed with 200 ng and 100 ng *** also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 *** mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit *** rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 *** the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and *** efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral *** procedures were performed at Rutgers under established Institutional Animal Care and Use protocols(eIACUC_TR201800022, approved on March 20, 2018).

关键词： amyotrophic lateral sclerosis injury motor function motor neuron PI3'kinase sciatic nerve suicide transport wortmannin

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security breach:peripheral nerves provide unrestricted access for toxin delivery into the central nervous system

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中国神经再生研究：英文版 2023年第1期18卷 64-67页

作者： Igor Lupinski allison sliang Randall D.McKinnon Department of Neurosurgery and Member The Cancer Institute of New JerseyRutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA

We explore the hypothesis that a potential explanation for the initiation of motor neuron disease is an unappreciated vulnerability in central nervous system defense,the direct delivery of neurotoxins into motor neurons via peripheral nerve retrograde *** further suggests a mechanism for focal initiation of neuro-degenerative diseases in general,with subsequent spread by network degeneration as suggested by the Frost-Diamond *** propose this vulnerability may be a byproduct of vertebrate evolution in a benign aquatic environment,where external surfaces were not exposed to concentrated neurotoxins.

关键词： amyotrophic lateral sclerosis bioaccumulation neurodegeneration neuropathology neurotoxins peripheral nerves retrograde transport retrotoxicity suicide transport

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A novel approach to Parkinson's disease treatment with a potentially dual-acting therapeutic agent that targetsα-synuclein aggregation and neuron death

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Neural Regeneration Research 2024年第12期19卷 2577-2578页

作者： allison RBalaj Hiroaki Kaku Department of Investigative Medicine Western Michigan University Homer Stryker MD School of MedicineKalamazooMIUSA

Parkinson's disease(PD),a prevalent neurodegenerative disorder,is chara cterized by the loss of dopaminergic neurons and the aggregation ofα-synuclein protein into Lewy *** the current standards of therapy have been successful in providing some symptom relief,they fail to address the underlying pathophysiology of PD and as a result,they have no effect on disease progression.

关键词： aggregation death therapeutic

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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： allison Loan Charvi syal Margarita Lui Ling He Jing Wang Regenerative Medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and Medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular Medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Wildfire severity alters soil microbial exoenzyme production and fungal abundances in the southern Appalachian Mountains

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Pedosphere 2024年第5期34卷 865-878页

作者： Megan L.sCHILL Richard BAIRD shawn P.BROWN allison M.VEACH Department of Integrative Biology University of Texas at San Antonio Biochemistry Molecular Biology Entomology and Plant Pathology Department Mississippi State University Department of Biological sciences The University of Memphis

Climate change has increased drought frequency and duration that are exacerbated by increased temperatures globally. This effect has, and will continue,to increase fire occurrence across many regions of North America. In the southern Appalachian Mountains, wildfires with high burn severity occurred in 2016due to increased drought and human activity. To investigate the effects of burn severity on soil physicochemical properties, microbial extracellular enzyme production, and microbial abundances in a temperate region, surface soils (0–15 cm) were collected from two sites (the Great smoky Mountains National Park in Tennessee and the Nantahala National Forest in North Carolina, UsA) spanning lightly, moderately, and severely burned areas, accompanied by adjacent unburned locations that act as controls. The soil samples were collected at three time points between 2017 and 2019 (i.e., 0.5, 1, and 2.5 years post-fire)among burn severity plots. Total hydrolytic enzyme production varied over time, with severe burn plots having significantly lower enzyme production at 2.5years post-fire. Individual enzymes varied among burn severities and across time post-fire. Light burn plots showed greater carbon-specific (β-glucosidase and β-xylosidase) and phosphorus-specific (acid phosphatase) enzyme activities at 0.5 years post-fire, but this effect was transient. At 2.5 years post-fire, theβ-xylosidase and acid phosphatase activities were lower in severe or moderate burn plots relative to the controls. In contrast, the activity of nitrogen-specific enzyme leucyl aminopeptidase was the lowest in severe burn plots at 0.5 years post-fire, but was the lowest in light burn plots at 2.5 years post-fire. The fungi:bacteria ratio declined with burn severity, indicating that fungi are sensitive or less resilient to high burn severity during recovery. These results suggest that wildfires alter trajectories for soil microbial structure and function within a 2.5-year timeframe, which potentially

关键词： 16s rRNA burn severity extracellular enzyme fungi:bacteria ratio internal transcribed spacer microbial structure

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Discussing menstrual health in family medicine

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Family Medicine and Community Health 2024年第2期12卷 23-26页

作者： allison R Casola Alice Renaud Ashwini Kamath Mulki Thomas Jefferson University sidney Kimmel Medical College PhiladelphiaPennsylvaniaUSA Lehigh Valley Health Network AllentownPennsylvaniaUSA Valley Health Partners Family Health Center AllentownPennsylvaniaUSA

MENsTRUAL HEALTH Menstrual health is a general biological marker for many cisgender women,transgender men and non-binary *** more than half of the population being people who menstruate,stigma,lack of conversation and pressing social needs around menstrual health persists throughout medicine.1 Discussions around menstruation and menstrual management can be difficult for individuals,whether it is with friends or family,or in the healthcare setting.1 Patients who have never discussed menstruation with a clinician may not know what is healthy,assume that an abnormal experience is normal and may endure periods that negatively affect their life,career or well-being.2–5 Menstruation plays a vital role in overall well-being and contributes significantly to an individual’s quality of *** their scope of care,family medicine clinicians are poised to identify red-flag menstrual symptoms in their routine visits with patients,reducing time to diagnosis of menstrual *** urge family medicine clinicians to have renewed conversations surrounding menstrual health with their *** purpose of this report is to supply a brief overview of the importance of menstrual communication in primary care and serve as a resource to enhance menstrual communication between patient and clinician,with the ultimate goal of decreasing menstrual stigma and promoting improved menstrual health and experiences for patients.

关键词： routine men spite

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Pollutants and fish predator/prey behavior： A review of laboratory and field approaches

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Current Zoology 2012年第1期58卷 9-20页

作者： Weis, Judith s. Candelmo, allison Department of Biological sciences Rutgers University Newark NJ 07102 USA National Marine Fisheries service NOAA James Howard Laboratory Sandy Hook Highlands NJ 07732 USA

Fish behavior can be altered by contaminants. There is an extensive literature on laboratory behavioral assays, with many chemicals impairing feeding or predator avoidance. However, there is not extensive work on fishes that live in contami- nated environments. Therefore, we then review our recent research on feeding and trophic relations of populations from contami- nated estuaries compared with relatively unpolluted sites. The mummichog Fundulus heteroclitus, is a non-migratory fish; those from more contaminated areas are poor predators and slower to capture active prey （grass shrimp, Palaemonetes pugio）. In the field, they consume much detritus and sediment, which is not nutritious. They are less active than fish from cleaner sites and more vulnerable to predation. They have altered thyroid glands and neurotransmitter levels, which may underlie altered behaviors Fish from the reference site kept in tanks with sediment and food from the polluted site showed bioaccumulation and reduced prey capture after two months, although fish from the polluted site did not show significant improvement when maintained in a clean environment. Poor nutrition and predator avoidance may be responsible for their being smaller and having a shorter life span than reference fish. Bluefish Pomatomus saltatrix, are a marine species in which the young-of-the-year spend their first summer in es- tuaries. We found bioaccumulation of contaminants and reduced activity, schooling, and feeding in young-of-the-year bluefish from a relatively unpolluted site that were fed prey fish from a contaminated site. They also had altered thyroid glands and neuro- transmitter levels. Many field-caught specimens had empty stomachs, which is rare in this species. In the fall, when they migrate back out to the ocean, they are smaller, slower, and more likely to starve or to be eaten than those that spent their summer in cleaner estuaries [Current Zoology 58 （1）： 9-20, 2012].

关键词： Predator Feeding Prey Pollution Activity Trophic

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A precise monitoring of snow surface height in the region of Lambert Glacier basin-Amery Ice shelf,East Antarctica

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science China Earth sciences 2005年第1期48卷 100-111页

作者： I.allison Australian Antarctic Division and Antarctic Climate and Ecosystems CRC

The net surface snow accumulation on the Antarctic ice sheet is determined by a combination of precipitation, sublimation and wind redistribution. We present a one-year record of hourly snow-height measurements at LGB69 (70°50's, 77°04'E, 1850 m a.s.l.). east side of Lambert Glacier basin (LGB), and 4 year record at G3 (70°53's, 69°52'E, 84 m a.s.l.), Amery Ice shelf (AIs). The measurements were made with ultrasonic sensors mounted on automatic weather stations installed at two sites. The snow accumulation at LGB69 is approximately 70 cm. Throughout the winter, between April and september, there was little change in surface snow height (ssH) at the two sites. The negative ssH change is due to densification at LGB69, and is due to both ablation and densification at G3. The strongest accumulation at two sites occurred during the period between October and March (accounting for 101.6% at LGB69), with four episodic increasing events occurring during 2002 for LGB69, and eight events during 1999-2002 for G3 (2 to 3 events per year). At LGB69, these episodic events coincided with obvious humidity 'pulses' and decreases of incoming solar radiation as recorded by the AWs. Observations of the total cloud amount at Davis station, 160 km NNE of LGB69, showed good correlation with major accumulation events recorded at LGB69. There was an obvious anti-correlation between the lowest cloud height at Davis and the daily accumulation rate at LGB69. Although there was no correlation over the total year between wind speed and accumulation at LGB69, large individual accumulation events are associated with episodes of strong wind (>7 m/s), we estimate drift snow may contribute to total ssH up to 35%. strong accumulation events at LGB69 are associated with major storms in the region and inland transport of moist air masses from the coast.

关键词： Antarctica, Lambert Glacier basin, Amery Ice shelf, accumulation, katabatic wind.

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Effect of organoclay loading on the dielectric properties and charge dynamics of a PP- rubber nanocomposite

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High Voltage 2020年第6期5卷 662-668页

作者： allison V.shaw Phichet Ketsamee Thomas Andritsch Alun s.Vaughan Tony Davis High Voltage Laboratory University of SouthamptonUK

The addition of organoclay to a polypropylene-rubber (PP-rubber) blend, primarily introduced to compatibilise the immiscible polymer blend, invokes contrasting dielectric and charge dynamic behaviour depending on the filler loading level. The authors report that at 0.5 wt.% loading, the organoclay decreases the DC conductivity, causes no significant dielectric losses, makes no significant difference to the space charge results compared to the unfilled system, and increases the reproducibility of the breakdown strength results, and hence the reliability of the material. These somewhat surprising results, contrasted by measurements of samples with 2.5 and 5 wt.%, lead us to conclude that trace amounts of organoclay improve the otherwise immiscible polymer blend making organoclay a suitable additive for HVDC applications.

关键词： loading rubber charge

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Newfound physiological function of FAIM protein offers hope of novel disease-modifying therapy for Alzheimer's disease

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Neural Regeneration Research 2023年第12期18卷 2677-2679页

作者： allison RBalaj Hiroaki Kaku Department of Investigative Medicine Western Michigan University Homer Stryker M.D.School of MedicineKalamazooMIUSA

Introduction of Fas apoptosis inhibitory molecule(FAIM): FAIM was originally discovered in FAsresistant mouse primary B lymphocytes in 1999, and was thought of as a FAs-apoptosis inhibitor based on overexpression studies(schneider et al., 1999). FAIM is an approximately 20 k Da intracellular protein, but a subsequent study identified an alternatively spliced form.

关键词： al. Alzheimer lymphocytes

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