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Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders

Translational Neurodegeneration 2014年第1期3卷 180-203,179页

作者： Kristi M Anderson katherine e olson katherine A estes Ken Flanagan Howard e Gendelman R Lee Mosley Department of Pharmacology and experimental Neuroscience Center for Neurodegenerative DisordersThe University of Nebraska Medical CenterOmahaNE 68198USA Prothena Biosciences Inc.650 Gateway BoulevardSouth San FranciscoCA 94080USA

Inappropriate T cell responses in the central nervous system(CNS)affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include,but are not limited to,multiple sclerosis,amyotrophic lateral sclerosis,Alzheimer’s disease and Parkinson’s *** the one hand immune responses can exacerbate neurotoxic responses;while on the other hand,they can lead to neuroprotective *** temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent ***,immune responses that affect neurodegeneration may occur within or outside the *** of antigen-specific CD4+T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal *** destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T ***,immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the *** responses with predominate T cell subtypes may differentially manifest migratory,regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific *** final result is altered glial and neuronal behaviors that influence the disease ***,discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.

关键词： Neurodegeneration Neuroprotection Migration MPTP MCAM Regulatory T cell effector T cell,Neuroinflammation

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An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety,tolerability,and immune biomarkers from limited case numbers

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Translational Neurodegeneration 2023年第1期12卷 529-545页

作者： katherine e.olson Mai M.Abdelmoaty Krista L.Namminga Yaman Lu Helen Obaro Pamela Santamaria R.Lee Mosley Howard e.Gendelman Department of Pharmacology and experimental Neuroscience Center for Neurodegenerative DisordersUniversity of Nebraska Medical CenterOmahaNE 68198USA Great Plains Center for Clinical and Translational Research Nebraska MedicineOmahaNEUSA Neurology Consultants of Nebraska PC and Nebraska MedicineOmahaNEUSA

Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s *** safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been *** As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 *** goals included numbers of CD4+T cells and monocytes and motor ***,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/*** 2 years,drug use was discon-tinued for 3 *** was then followed by an additional 6 months of *** Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone *** drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term *** Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were *** the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin *** finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile *** Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim *** in larger patient populations is planned in a future phase II evaluation.

关键词： Parkinson’s disease Granulocyte-macrophage colony-stimulating factor Unified Parkinson’s Disease Rating Scale Regulatory T cells Neuroprotection Sargramostim therapy

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Structural and Optical Properties and emerging Applications of Metal Nanomaterials

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Journal of Materials Science & Technology 2008年第4期24卷 433-446页

作者： Tammg Y.olson Department of Chemistry and Biochemistry University of CaliforniaSanta CruzCA 95064USA

Nanomaterials possess intriguing optical properties that depend sensitively on size, shape, and material content of the structures. Controlling such structural characteristics of the nanostructures allows the tailoring of their physical and chemical properties, e.g. optical, electronic, and catalytic, to achieve what is desired lot specific applications of interest. This review will cover the development of various shapes for silver and gold nanomaterials with emphasis on their relation to optical properties. examples of various modern synthetic methods and characterization techniques are highlighted. The influence of the metal nanomaterial＇s shape and optical absorption on surface enhanced Raman scattering （SeRS） and a final note on new emerging applications of metal nanostructures are also discussed.

关键词： Nanomaterial Metal nanostructure Optical properties Size and shape effect

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Journey Through the Groan Zone with Academics and Practitioners: Bridging Conflict and Difference to Strengthen Disaster Risk Reduction and Recovery Work

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International Journal of Disaster Risk Science 2018年第3期9卷 421-428页

作者： katherine e.Browne Caela O'Connell Laura Meitzner Yoder Department of Anthropology Colorado State University Department of Anthropology – Disasters Displacement and Human Rights Program University of Tennessee Program in Human Needs and Global Resources Wheaton College

Academic-practitioner divides in disaster management and research can be persistent and pernicious,bearing consequences for disaster survivors and future affected populations. The gap between disaster professionals and academic researchers is often treated as an unavoidable structural problem or a neutral accident of professional silos and circumstance. We suggest that these gaps are not neutral, and that they can and must be overcome. With hundreds of millions of people affected by disaster each year and recovery costs skyrocketing, there is urgency in connecting researcher and practitioner knowledges to avoid expensive mistakes and most importantly, to decrease human suffering. Yet the difficulties that US academic anthropologists and practitioners experienced in their efforts to collaborate became evident in a cross-sector National Science Foundation(NSF)-funded workshop on the relevance of culture in disaster work. We suggest and illustrate how more systematic cross-field communication can be operationalized through engaging in an ongoing and relational process of bridging. Such a process can offer long-term benefits to the people and institutions involved,dramatically enhance the science of disaster management,and help reduce the social and material costs of disaster impacts.

关键词： Academic and practitioner divide Applied research Cross-sector communication Culture and disaster Disaster anthropology Disaster management

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Surgery for oligometastasis of pancreatic cancer

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Chinese Journal of Cancer Research 2015年第4期27卷 358-367页

作者： Fengchun Lu katherine e.Poruk Matthew J.Weiss Department of General Surgery Union Hospital Fujian Medical University Department of Surgery The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine

The incidence of pancreatic adenocarcinoma（PDAC） has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy（PM） has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

关键词： Pancreatic cancer(PC) oligometastasis hepatic metastasis pulmonary metastasis surgical management

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Arabidopsis FtsZ2-1 and FtsZ2-2 Are Functionally Redundant, But FtsZ-Based Plastid Division Is Not essential for Chloroplast Partitioning or Plant Growth and Development

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Molecular Plant 2009年第6期2卷 1211-1222页

作者： Aaron J. Schmitz Jonathan M. Glynn Bradley J.S.C. olson Kevin D. Stokes katherine W. Osteryoung Department of Plant Biology 166 Plant Biology Bldg Michigan State University East Lansing MI 48824-1312 USA Cell and Molecular Biology Program Michigan State University East Lansing MI 48824 USA Department of energy-Plant Research Laboratory Michigan State University East Lansing MI 48824 USA Genetics Program Michigan State University East Lansing MI 48824 USA Biochemistry and Molecular Biology Program Michigan State University East Lansing MI 48824 USA Present address: The Salk Institute for Biological Studies Plant Molecular and Cellular Biology Laboratory La Jolla CA 92037 USA Present address: Mycobacteria and Brucella Section NVSL/APHIS/USDA 1920 Dayton Ave Ames IA 50010 USA

FtsZ1 and FtsZ2 are phylogenetically distinct families of FtsZ in plants that co-localize to mid-plastid rings and facilitate division of chloroplasts. In plants, altered levels of either FtsZ1 or FtsZ2 cause dose-dependent defects in chloroplast division; thus, studies on the functional relationship between FtsZgenes require careful manipulation of FtsZ levels in vivo. To define the functional relationship between the two FtsZ2 genes in Arabidopsis thaliana, FtsZ2-1 and FtsZ2-2, we expressed FtsZ2-1 in an ftsZ2-2 null mutant, and vice versa, and determined whether the chloroplast division defects were rescued in plants expressing different total levels of FtsZ2. Full rescue was observed when either the FtsZ2-1 or FtsZ2-2 level approximated total FtsZ2 levels in wild-type （WT）. Additionally, FtsZ2-2 interacts with ARC6, as shown previously for FtsZ2- 1. These data indicate that FtsZ2-1 and FtsZ2-2 are functionally redundant for chloroplast division in Arabidopsis. To rigorously validate the requirement of each FtsZ family for chloroplast division, we replaced FtsZ1 with FtsZ2 in vivo, and vice versa, while maintaining the FtsZ level in the transgenic plants equal to that of the total level in WT. Chloroplast division defects were not rescued, demonstrating conclusively that FtsZ1 and FtsZ2 are non-redundant for maintenance of WT chloroplast numbers. Finally, we generated ftsZtriple null mutants and show that plants completely devoid of FtsZ protein are viable and fertile. As plastids are presumably essential organelles, these findings suggest that an FtsZ-independent mode of plastid partitioning may occur in higher plants.

关键词： Chloroplast plastid division FtsZ ARC6 PDV1.

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Different paths to sexual size dimorphism in two praying mantids, Pseudomantis albofimbriata and Hierodula majuscula

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Insect Science 2014年第2期21卷 227-233页

作者： Louise e. Allen katherine L. Barry Gregory I. Holwell Department of Biological Sciences Macquarie University North Ryde NSW 2109 Australia School of Biological Sciences The University of Auckland Auckland New Zealand

Sexual size dimorphism （SSD） is widespread among diverse animal taxa and has attracted the attention of evolutionary biologists for over a century. SSD is likely to be adaptive and the result of divergent selection on different size optima for males and females, given their different roles in reproduction. The developmental trajectory leading to SSD may help us to understand how selection acts on male and female size. Here, we describe the growth and development of two Australian praying mantids, Pseudomantis albofimbriata and Hierodula majuscula including the number of moults, time to adulthood, size at each moult, and the degree of SSD. While both species exhibit the common pattern of female-biased SSD, the number of moults required for individuals to reach adulthood differed between males and females and between species. Despite their larger adult size, P. albofimbriata females require fewer moults and less time than males to reach adulthood, but are significantly larger than males from the second instar onwards. In contrast, H. majuscula males reached adulthood in fewer moults, and less time than females, however males and females did not differ in size until females went through their final moult into adulthood. H. majuscula also required more time and more moults to reach adulthood than 17. albofimbriata. We discuss these different developmental pathways in light of the existing knowledge of reproductive biology for each species. We also suggest that these differences may relate to the different phenologies that occur in strongly seasonal temperate environments compared with those in the tropics. This study provides evidence that SSD can result from two different patterns of growth and development in closely related species.

关键词： developmental trajectories Mantodea sexual size dimorphism

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Two-dimensional d-πconjugated metal-organic framework based on hexahydroxytrinaphthylene

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Nano Research 2021年第2期14卷 369-375页

作者： Zheng Meng katherine A.Mirica Department of Chemistry Burke Laboratory41 College Streety Dartmouth CollegeHanoverNH 03755USA

The development of new two-dimensional(2D)d-πconjugated metal-organic frameworks(MOFs)holds great promise for the construction of a new generation of porous and semiconductive *** paper describes the synthesis,structural characterization,and electronic properties of a new d-πconjugated 2D MOF based on the use of a new ligand 2,3,8,9,14,*** reticular self-assembly of this largeπ-conjugated organic building block with Cu(II)ions in a mixed solvent system of 1,3-dimethyl-2-imidazolidinone(DMI)and H2 O with the addition of ammonia water or ethylenediamine leads to a highly crystalline MOF Cu3(HHTN)2,which possesses pore aperture of 2.5 ***3(HHTN)2 MOF shows moderate electrical conductivity of 9.01×10^(-8)S·cm^(-1)at 385 K and temperature-dependent band gap ranging from 0.75 to 1.65 *** chemical oxidation by l2,the conductivity of Cu3(HHTN)2 can be increased by 360 *** access to HHTN based MOF adds an important member to previously reported MOF systems with hexagonal lattice,paving the way towards systematic studies of structure-property relationships of semiconductive MOFs.

关键词： two-dimensional metal-organic framework(MOF) trinaphthylene conductive MOF

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Plasmon point spread functions： How do we model plasmon-mediated emission processes？

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Frontiers of physics 2014年第1期9卷 3-16页

作者： katherine A. Willets Department of Chemistry University of Texas at AustinWelch Hall 1.202 105 E 2~TH ST. STOP A5300 Austin TX 78712 USA

A major challenge with studying plasmon-mediated emission events is the small size of plasmonic nanoparticles relative to the wavelength of light. Objects smaller than roughly half the wavelength of light will appear as diffraction-limited spots in far-field optical images, presenting a significant experimental challenge for studying plasmonic processes on the nanoscale. Super-resolution imaging has recently been applied to plasmonic nanosystems and allows plasmon-mediated emission to be resolved on the order of ~5 nm. In super-resolution imaging, a diffraction-limited spot is fit to some model function in order to calculate the position of the emission centroid, which represents the loca- tion of the emitter. However, the accuracy of the centroid position strongly depends on how well the fitting function describes the data. This Perspective discusses the commonly used two-dimensional Gaussian fitting function applied to super-resolution imaging of plasmon-mediated emission, then introduces an alternative model based on dipole point spread flmctions. The two fitting models are compared and contrasted for super-resolution imaging of nanoparticle scattering/luminescence, surface-enhanced Raman scattering, and surface-enhanced fluorescence.

关键词： plasmon point spread function dipole super-resolution surface-enhanced Ramanscattering (SeRS)

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Understanding the sources and composition of the incremental excess of fine particles across multiple sampling locations in one air shed

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Journal of environmental Sciences 2014年第4期26卷 818-826页

作者： Jerome e.McGinnis Jongbae Heo Michael R.olson Andrew P.Rutter James J.Schauer University of Wisconsin-Madison Environmental Chemistry and Technology Program Wisconsin State Laboratory of Hygiene

Well-designed health studies and the development of effective regulatory policies need to rely on an understanding of the incremental differences in particulate matter concentrations and their sources. Although only a limited number of studies have been conducted to examine spatial differences in sources to particulate matter within an air shed, routine monitoring data can be used to better understand these differences. Measurements from the US ePA Chemical Speciation Network （CSN） collected between 2002-2008 were analyzed to demonstrate the utility of regulatory data across three sites located within 100 km of each other. Trends in concentrations, source contribution, and incremental excesses across three sites were investigated using the Positive Matrix Factorization model. Similar yearly trends in chemical composition were observed across all sites, however, excesses of organic matter and elemental carbon were observed in the urban center that originated from local emissions of mobile sources and biomass buming. Secondary sulfate and secondary nitrate constituted over half of the PM2.5 with no spatial differences observed across sites. For these components, the excess of emissions from industrial sources could be directly quantified. This study demonstrates that CSN data from multiple sites can be successfully used to derive consistent source profiles and source contributions for regional pollution, and that CSN data can be used to quantify incremental differences in source contributions of across these sites. The analysis strategy can be used in other regions of the world to take advantage of existing ambient particulate matter monitoring data to better the understanding of spatial differences in source contributions within a given air shed.

关键词： CSN Incremental excess PMFPM2.5

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