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

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Neural Regeneration Research 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

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

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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

Backdoor intrusion: retrotoxicity can explain targeted motor neuron death in amyotrophic lateral sclerosis

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Neural Regeneration Research 2021年第7期16卷 1448-1448页

作者： randall d.mckinnon department of Neurosurgery and Member The Cancer Institute of New JerseyRutgers-Robert Wood Johnson Medical SchoolPiscatawayNJUSA

To the editor: Amyotrophic lateral sclerosis(ALS) is a fatal disease of unknown cause that selectively targets brain and spinal cord motor neurons(MNs).The lifetime risk is 1 in 2000, and most cases are sporadic although up to 10% of patients are predisposed by familial mutations in MN protection or repair genes(Bruijn et al., 2004).Risk factors include agrochemical exposure and trauma(Walters et al., 2019), although why they target MN is *** are at a greater risk than non-farming rural residents(Kang et al, 2014), and ALS clusters occur in abrasion prone activities conducted on agrochemical treated fields such as baseball and soccer(Chio et al., 2005).

关键词： al. editor Walter

Visual rating and the use of image analysis for assessing canopy density in a pecan provenance collection during leaf fall

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Journal of Forestry Research 2023年第6期34卷 1843-1854页

作者： Cristina Pisani Clive H.Bock Jennifer randall United States department of Agriculture−Agricultural Research Service (USDA-ARS)Southeastern Fruit and Tree Nut Research Station(SEFTNRS)ByronGA 31008USA department of Entomology Plant Pathology and Weed ScienceNew Mexico State UniversityLas CrucesNM 88003USA

A collection representing the native range of pecan was planted at the US dA-ARS Southeastern Fruit and Tree Nut Research Station,Byron,*** collection(867 trees)is a valuable genetic resource for characterizing important horticultural *** density during leaf fall is important as the seasonal canopy dynamics provides insights to environmental cues and breeding potential of *** ability of visual raters to estimate canopy density on a subset of the provenance collection(76 trees)as an indicator of leaf shed during autumn along with image analysis values was *** canopy density using the image analysis software was less compared to visual estimates(11.9%vs 18.4%,respectively).At higher canopy densities,the raters overestimated foliage density,but overall agreement between raters and measured values was good(ρc=0.849 to 0.915),and inter-rater reliability was high(R^(2)=0.910 to 0.953).The provenance from Missouri(MOL),the northernmost provenance,had the lowest canopy density in November,and results show that the higher the latitude of the provenance,the lower the canopy *** on regression,the source provenance latitude explained 0.609 of the variation using image analysis,and0.551 to 0.640 when based on the rater estimates of canopy *** assessment of pecan canopy density due to late season leaf fall for comparing pecan genotypes provides accurate and reliable estimates and could be used in future studies of the whole provenance collection.

关键词： Carya illinoinensis Accuracy Reliability Canopy Foliage density Leaf area density Leaf area index

Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling:Influence of smoking

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World Journal of Gastroenterology 2006年第28期12卷 4485-4491页

作者： Rhonda M Brand david d Jones Henry T Lynch randall E Brand Patrice Watson Ramesh Ashwathnayaran Hemant K Roy department of Internal Medicine Evanston Northwestern Healthcare and Feinberg School of Medicine at Northwestern UniversityEvanston ILUinted States department of Biological Systems Engineering University of Nebraska-LincolnLincoln NEUinted States Hereditary Cancer Institute Creighton UniversityUinted States

AIM： To investigate whether a fuzzy logic model could predict colorectal cancer （CRC） risk engendered by smoking in hereditary non-polyposis colorectal cancer （HNPCC） patients. METHOdS： Three hundred and forty HNPCC mismatch repair （MMR） mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation （hMLH1 or hMSH2）, gender, and smoking status on the probability of developing CRC. RESULTS： Smoking significantly increased CRC risk in male hMSH2 mutation carriers （P 〈 0.05）. hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males （P 〈 0.05）. Males had a significantly higher risk of CRC than females for hMLH1 non smokers （P 〈 0.05）, hMLH1 smokers （P 〈 0.1） and hMSH2 smokers （P 〈 0.1）. Smoking promoted CRC in a dose-dependent manner in hMSH2 in males （P 〈 0.05）. Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history （P 〈 0.05）. CONCLUSION： CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

关键词： Hereditary non-polyposis colorectal cancer Lynch syndrome Smoking Colorectal cancer Fuzzy modeling Risk assessment

INTEGRATION OF THE MOdELS OF ANNAGNPS ANd REMM TO ASSESS RIPARIAN BUFFER SYSTEM FOR SEdIMENT REdUCTION

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International Journal of Sediment Research 2007年第1期22卷 60-69页

作者： Ronald BINGNER randall WILLIAMS Richard LOWRANCE david BOSCH Joe SHERIdAN Ph.d Agricultural Engineer USDA-Agricultural Research Science -National Sedimentation Laboratory P.O. Box 1157 Oxford MS 38655 USA Agricultural Engineer USDA-Agricultural Research Science -National Sedimentation Laboratory 2316 RAINWATER RD TIFTON GA 31793 Ph.d Ecologist USDA-Agricultural Research Service-Southeast Watershed Research Laboratory P.O. Box 748 2379 Rainwater Road Tifton Georgia 31793 USA Ph.d Research Hydraulic Engineer USDA-Agricultural Research Service-Southeast Watershed Research Laboratory P.O. Box 748 2316 RAINWATER RD Tifton Georgia 31793 Ph.d Research Hydraulic Engineer USDA-Agricultural Research Service-Southeast Watershed Research Laboratory P.O. Box 748 2316 RAINWATER RD Tifton Georgia 31793

The United States department of Agriculture (USdA) Annualized Agricultural Non-Point Source Pollution model (AnnAGNPS) is used to help evaluate a watershed response to agricultural management practices to control water quality. However, AnnAGNPS version 3.5 does not contain features to estimate the effect of a riparian buffer (RB) system on water quality. The Riparian Ecosystem Management Model (REMM) is used to simulate the impact of riparian buffer systems on water quality. However, frequently the lack of measured upland loadings that are required by REMM simulation limits the application of REMM. To address this data gap, a study was conducted to integrate AnnAGNPS with REMM for RB system simulation. AnnAGNPS was used to simulate water and sediment loadings from an upland field into a three-zone RB system at the Gibbs Farm located in the Georgia coastal plain. These AnnAGNPS outputs were used as the inputs to REMM. REMM was used to simulate water and sediment movement along the riparian buffers. The AnnAGNPS simulated amount of annual runoff at the edge of the field was close to observed amounts (Nash-Sutcliffe efficiency of 0.92). It is believed that a substantial portion of sand was removed from the runoff one meter into the grass buffer where the samplers were located; therefore, sand was excluded from the AnnAGNPS simulation for comparison with observed sediment. Excluding sand, the AnnAGNPS predicted amount of annual sediment matches the observed amount fairly well (Nash-Sutcliffe efficiency of 0.46). In addition, based on evaluating the percent reduction of sediment at each zonal interface, the AnnAGNPS/REMM model well simulated the function of the RB system to reduce sediment.

关键词： AnnAGNPS REMM Watershed modeling Riparian buffer systems Runoff Sediment simulation

Optimal designs for Genomic Selection in Hybrid Crops

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Molecular Plant 2019年第3期12卷 390-401页

作者： Tingting Guo Xiaoqing Yu Xianran Li Haozhe Zhang Chengsong Zhu Sherry Flint-Garcia Michael d.McMullen James B.Holland Stephen J.Szalma randall J.Wisser Jianming Yu department of Agronomy Iowa State UniversityAmesIA50011USA department of Statistics Iowa State UniversityAmesIA50011USA USdA-ARS and division of Plant Sciences University of MissouriColumbiaMO65211USA USdA-ARS and department of Crop and Soil Sciences North Carolina State UniversityRaleighNC27695USA department of Plant and Soil Sciences University of DelawareNewarkDE19716USA

Improved capacity of genomics and biotechnology has greatly enhanced genetic studies in different areas. Genomic selection exploits the geno type-to-phe no type relationship at the whole-ge nome level and is being implemented in many crops? Here we show that design-thinking and data-mining techniques can be leveraged to optimize genomic prediction of hybrid performance? We phenotyped a set of 276 maize hybrids generated by crossing founder inbreds of nested association mapping populations for flowering time, ear height, and grain yield? With 10 296 310 SNPs available from the parental inbreds, we explored the pat? terns of genomic relati on ships and phenotypic variation to establish training samples based on clustering, graphic n etwork analysis, and genetic mating scheme ? Our analysis showed that training set desig ns outperformed random sampling and earlier methods that either minimize the mean of prediction error variance or maximize the mean of generalized coefficient of determination. Additional analyses of 2556 wheat hybrids from an early-stage hybrid breeding system and 1439 rice hybrids from an established hybrid breeding system validated the approaches. Together, we dem on strated that effective genomic predicti on models can be established with a training set 2%-13% of the size of the whole set, enabling an efficient exploration of enormous inf ere nee space of gen etic combi nations.

关键词： data mining molecular breeding genomic relationship genomic selection optimal design

Characterization and transcriptional analyses of cdNAs encoding three trypsin- and chymotrypsin-like proteinases in CrylAb-susceptible and CrylAb-resistant strains of sugarcane borer, diatraea saccharalis

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Insect Science 2013年第4期20卷 485-496页

作者： Yunlong Yang Yu Cheng Zhu James Ottea Claudia Husseneder B. Rogers Leonard Craig Abel randall Luttrell Fangneng Huang department of Entomology Louisiana State University Agricultural Center Baton Rouge Louisiana Southern Insect Management Research Unit Agricultural Research Service United States Department of Agriculture Stoneville Mississippi Corn Insects and Crop Genetics Research Unit Agricultural Research Service United States Department of Agriculture Ames Iowa USA

diatraea saccharalis is a major corn borer pest. Midgut serine proteinases are essential for insect growth and development. Alteration of midgut proteinases is re- sponsible for Bt resistance development in some species. To clone midgut trypsin and chymotrypsin cdNAs and to test if the CrylAb resistance in d. saccharalis is associ- ated with changes in midgut proteinases, total midgut tryptic and chymotryptic activities, cdNA sequences, and gene expressions of three trypsin and three chymotrypsin genes were comparatively examined between Cry 1 Ab-susceptible （Cry 1 Ab- S S） and Cry 1 Ab-resistant （Cry 1 Ab-RR） strains. Full-length cdNAs encoding three trypsin- and three chymotrypsin- like proteinases were sequenced from CrylAb-SS and CrylAb-RR larvae. These cdNAs code for active forms of midgut serine proteinases with all fimctional motifs, includ- ing signal peptide, conserved His-Asp-Ser for the catalytic triad, three pairs of cysteines for disulfide bridge configurations, and conserved substrate specificity determination residues. In general, cdNA and putative protein sequences are highly similar between CrylAb-SS and CrylAb-RR strains, except for a few nucleotide and predicted amino acid substitutions, whose function need to be further clarified. Total trypsin and chymotrypsin activities were also similar between CrylAb-SS and CrylAb-RR strains. Transcriptional levels of the trypsin and chymotrypsin genes had numerical difference between Cry 1 Ab-SS and CrylAb-RR strains, but the difference was not statistically significant. data suggest that the development of CrylAb resistance in d. saccharalis was not significantly as- sociated with these trypsins and chymotrypsins. Results clarified the role of six midgut proteinases and provided a foundation for continuing examination of potential involvement of other midgut proteinases in Bt resistance development and other important biochemical processes.

关键词： Bt cdNA chymotrypsin enzymatic activity resistance trypsin

Potential legacy effects of biofuel cropping systems on soil microbial communities in southern Wisconsin, USA

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Agricultural Sciences 2011年第2期2卷 131-137页

作者： Chao Liang Gregg R. Sanford randall d. Jackson Teri C. Balser 不详

Soil microbial community structure is clearly linked to current plant species composition, but less is known about the legacy effects of plant species and agricultural management practices on soil microbial communities. Using microbial lipid biomarkers, we assessed patterns of com-munity-level diversity and abundance at depths of 0-10 and 10-25 cm from three hay (al-falfa/orchardgrass) and two corn plots in south ern Wisconsin. Principal components analysis of the lipid biomarkers revealed differential composition of the soil microbial communities at the two depths. despite similar abundance of fungi, bacteria, actinomycete, protozoa, and total microbial lipids in the hay and corn at 0-10 cm, community structure differed with a sig-nificantly higher absolute abundance of arbus-cular mycorrhizal fungi and gram-negative bacteria in the hay plots. No significant micro-bial lipid mass differences were detected be-tween the two management regimes at 10-25 cm, but the proportional dominance of bacterial gram type differed with depth. These results indicate the potential for legacy effects of an-nual and perennial cropping systems manage-ment on microbial community composition and suggests the importance of considering past land-use when initiating long-term agroecolo- gical trials.

关键词： Lipid Biomarker Alfalfa Hay Corn Agroecosystem