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Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

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Advances in Nanoparticles 2012年第3期1卷 44-53页

作者： Nicholas j. Wiley A. B. Madhankumar Ryan M. Mitchell Elizabeth B. Neely Elias Rizk Gregory L. Douds zachary Simmons james R. Connor Department of Neurology Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA George M. Leader Family Laboratory Department of Neurosurgery Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA

Activation of microglia is a histological feature observed in neurodegenerative diseases like ALS. The oral administration of minocycline has been demonstrated to have minimal neuroprotection ability in the animal models and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows promise in a number of disease models suggesting it could be effective if delivered optimally. Thus, we utilized LPS modified liposomes to target TLR4 receptor on the microglia in SOD1G93A mice and compared its efficacy with non- targeted nanoliposomes. The in vitro results indicate that targeting the TLR4 receptor on microglia significantly increases (p G93A mouse model of ALS, targeted and non-targeted minocycline treatment significantly increased (p G93A mice, the non- targeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

关键词： Amyotrophic Lateral Sclerosis Minocycline Liposomes Microglia TLR4 Lipopolysaccharides

Maize Gene Regulatory Network for Phenolic Metabolism

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Molecular Plant 2017年第3期10卷 498-515页

作者： Fan Yang Wei Li Nan jiang Haidong Yu Kengo Morohashi Wilberforce zachary Oumal Daniel E. Morales-Mantilla Fabio Andres Gomez-Canol Eric Mukundi Luis Daniel Prada-Salcedo Roberto Alers Velazquez jasmin Valentin Maria Katherine Mejia-Guerra john Gray Andrea I. Doseff Erich Grotewold Center for Applied Sciences (CAPS) Department of Molecular Genetics Department of Physiology and Cell Biology Heart and Lung Research Institute Molecular Cellular and Developmental Biology (MCDB) Graduate Program Success in Graduate Education (SiGuE) Program The Ohio State University Columbus OH 43210 USA Department of Biological Sciences University of Toledo Toledo OH 43560 USA

The translation of the genotype into phenotype, represented for example by the expression of genes encod- ing enzymes required for the biosynthesis of phytochemicals that are important for interaction of plants with the environment, is largely carried out by transcription factors （TFs） that recognize specific cis-regulatory elements in the genes that they control. TFs and their target genes are organized in gene regulatory net- works （GRNs）, and thus uncovering GRN architecture presents an important biological challenge necessary to explain gene regulation. Linking TFs to the genes they control, central to understanding GRNs, can be car- ried out using gene- or TF-centered approaches. In this study, we employed a gene-centered approach uti- lizing the yeast one-hybrid assay to generate a network of protein-DNA interactions that participate in the transcriptional control of genes involved in the biosynthesis of maize phenolic compounds including gen- eral phenylpropanoids, lignins, and flavonoids. We identified 1100 protein-DNA interactions involving 54 phenolic gene promoters and 568 TFs. A set of 11 TFs recognized 10 or more promoters, suggesting a role in coordinating pathway gene expression. The integration of the gene-centered network with informa- tion derived from TF-centered approaches provides a foundation for a phenolics GRN characterized by in- terlaced feed-forward loops that link developmental regulators with biosynthetic genes.

关键词： phenylpropanoid flavonoid yeast one-hybrid chromatin immunoprecipitation

Scalable and automated CRISPR-based strain engineering using droplet microfluidics

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Microsystems & Nanoengineering 2022年第2期8卷 227-236页

作者： Kosuke Iwai Maren Wehrs Megan Garber jess Sustarich Lauren Washburn zachary Costello Peter W.Kim David Ando William R.Gaillard Nathan j.Hillson Paul D.Adams Aindrila Mukhopadhyay Hector Garcia Martin Anup K.Singh Technology Division DOE Joint BioEnergy InstituteEmeryvilleCA 94608USA Biotechnology and Bioengineering Department Sandia National LaboratoriesLivermoreCA 94550USA Biofuels and Bioproducts Division DOE Joint BioEnergy InstituteEmeryvilleCA 94608USA Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Molecular Biophysics and Integrated Bioimaging Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Bioengineering University of CaliforniaBerkeleyCA 94720USA BCAM Basque Center for Applied MathematicsBilbao 48009Spain

We present a droplet-based microfluidic system that enables CRISPR-based gene editing and high-throughput screening on a *** microfluidic device contains a 10x10 element array,and each element contains sets of electrodes for two electric field-actuated operations:electrowetting for merging droplets to mix reagents and electroporation for *** device can perform up to 100 genetic modification reactions in parallel,providing a scalable platform for generating the large number of engineered strains required for the combinatorial optimization of genetic pathways and predictable *** demonstrate the system's capabilities through the CRISPR-based engineering of two test cases:(1)disruption of the function of the enzyme galactokinase(galK)in£coli and(2)targeted engineering of the glutamine synthetase gene(glnA)and the blue-pigment synthetase gene(bpsA)to improve indigoidine production in£coli.

关键词： operations generating fluid

Evading the host response:Staphylococcus“hiding”in cortical bone canalicular system causes increased bacterial burden

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Bone Research 2020年第4期8卷 447-457页

作者： Stephen D.Zoller Vishal Hegde zachary D.C.Burke Howard Y.Park Chad R.Ishmael Gideon W.Blumstein William Sheppard Christopher Hamad Amanda H.Loftin Daniel O.johansen Ryan A.Smith Marina M.Sprague Kellyn R.Hori Samuel j.Clarkson Rachel Borthwell Scott I.Simon jeff F.Miller Scott D.Nelson Nicholas M.Bernthal Department of Orthopedic Surgery University of CaliforniaLos Angeles125016th St Suite 2100Santa MonicaCA 90404USA David Geffen School of Medicine University of CaliforniaLos Angeles10833 Le Conte AveLos AngelesCA 90095USA Department of Internal Medicine University of CaliforniaLos Angeles757 Westwood PlazaSuite 7501Los AngelesCA 90095USA Department of Biomedical Engineering University of CaliforniaDavisDavisCA 95616USA California NanoSystems Institute University of CaliforniaLos Angeles570 Westwood PlazaLos AngelesCA 90095USA Department of Microbiology Immunologyand Molecular GeneticsDavid Geffen School of MedicineUniversity of CaliforniaLos Angeles 90095USA Department of Pathology University of CaliforniaLos Angeles125016th St Suite 3450Santa MonicaCA 90404USA

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone *** persists as to the optimal void filler for this“limb salvage”surgery,whether metal or allograft *** focus on optimizing important functional gains for patients,and the risk of devastating implant infection has been thought to be similar regardless of implant *** insights into infection pathophysiology are challenging this equipoise,however,with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus(the most common infecting agent)into the host lacunar–canaliculi network,and also clinical data revealing a higher rate of infection of allograft over *** current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and ***-time Staphylococci infection characteristics were quantified in cortical bone vs metal,and both microarchitecture of host implant and presence of host immune response were *** orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous *** establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone *** study results reveal a mechanism by which Staphylococci evasion of host immunity is possible,contributing to elevated risks of infection in cortical *** presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

关键词： immunity insight reservoir

大视野成像血细胞计数对微量体液的快速与智能诊断

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大视野成像血细胞计数对微量体液的快速与智能诊断

Single low-dose lipopolysaccharide preconditioning:neuroprotective against axonal injury and modulates glial cells

中国化学会第30届学术年会

作者：高婷娟 zachary j Smith james Hood Sebastian Wachsmann-Hogiu UC Davis Health System 华中师范大学

便携式血细胞计数是床旁诊断（POCT）中一个急待突破的领域。参照智能、廉价、微创等终极目标,流式细胞术和库尔特原理对开发便携式血细胞计数显示了其技术局限性。鉴于此种现状,我们开发了一套"血细胞大视场显微成像计数"光学系统,运... 详细信息

便携式血细胞计数是床旁诊断（POCT）中一个急待突破的领域。参照智能、廉价、微创等终极目标,流式细胞术和库尔特原理对开发便携式血细胞计数显示了其技术局限性。鉴于此种现状,我们开发了一套"血细胞大视场显微成像计数"光学系统,运用单个荧光标记对血样染色,同时记录明场与荧光成像,并采用计算机程序对成像进行分析。这套仪器与方法可以准确的计数红细胞、血小板、白细胞及其三分类和血红蛋白。整个诊断过程只需15分钟和少至0.5微升的临床样品。初步临床试验对人体四种体液的诊断取得成功,这套方法还被拓展到其他哺乳动物包括马、牛、猫、狗的血液诊断中,均获得了良好效果。我们期待这套仪器与方法转化并过渡到临床应用研究,为开发便携式血液诊断提供有效的思路和技术支持。

关键词：床旁诊断血细胞计数便携式显微成像成像分析

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Neuroimmunology and Neuroinflammation 2017年第1期4卷 6-15页

作者： Ryan C.Turner zachary j.Naser Brandon P.Lucke-Wold Aric F.Logsdon Reyna L.Vangilder Rae R.Matsumoto jason D.Huber Charles L.Rosen Department of Neurosurgery West Virginia UniversitySchool of MedicineMorgantownWV26506USA Center for Neuroscience West Virginia UniversitySchool of MedicineMorgantownWV 26506USA Department of Basic Pharmaceutical Sciences West Virginia UniversitySchool of PharmacyMorgantownWV 26506USA Center for Health Restoration West Virginia UniversitySchool of NursingMorgantownWV 26506USA

Aim:Over 7 million traumatic brain injuries (TBI) are reported each year in the United ***,treatments and neuroprotection following TBI are limited because secondary injury cascades are poorly *** (LPS) administration before controlled cortical impact can contribute to ***,the underlying mechanisms and whether LPS preconditioning confers neuroprotection against closed-head injuries remains ***:The authors hypothesized that preconditioning with a low dose of LPS (0.2 mg/kg) would regulate glial reactivity and protect against diffuse axonal injury induced by weight *** was administered 7 days prior to *** administration reduced locomotion,which recovered completely by time of ***:LPS preconditioning significantly reduced the post-injury gliosis response near the corpus callosum,possibly by downregulating the oncostatin M *** novel findings demonstrate a protective role of LPS preconditioning against diffuse axonal *** preconditioning successfully prevented neurodegeneration near the corpus callosum,as measured by fluorojade ***:Further work is required to elucidate whether LPS preconditioning confers long-term protection against behavioral deficits and to elucidate the biochemical mechanisms responsible for LPS-induced neuroprotective effects.

关键词： Lipopolysaccharide preconditioning oncostatin M receptor diffuse axonal injury gliosis neuroprotection

The joint automated repository for various integrated simulations (jARVIS) for data-driven materials design

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npj Computational Materials 2020年第1期6卷 234-246页

作者： Kamal Choudhary Kevin F.Garrity Andrew C.E.Reid Brian DeCost Adam j.Biacchi Angela R.Hight Walker zachary Trautt jason Hattrick-Simpers A.Gilad Kusne Andrea Centrone Albert Davydov jie jiang Ruth Pachter Gowoon Cheon Evan Reed Ankit Agrawal Xiaofeng Qian Vinit Sharma Houlong Zhuang Sergei V.Kalinin Bobby G.Sumpter Ghanshyam Pilania Pinar Acar Subhasish Mandal Kristjan Haule David Vanderbilt Karin Rabe Francesca Tavazza Materials Measurement Laboratory National Institute of Standards and TechnologyGaithersburgMD 20899USA Theiss Research La JollaCA 92037USA Department of Chemistry and Biochemistry University of MarylandCollege ParkMD 20742USA Physical Measurement Laboratory National Institute of Standards and TechnologyGaithersburgMD 20899USA Materials and Manufacturing Directorate Air Force Research LaboratoryWright–Patterson Air Force BaseDaytonOH 45433USA Department of Materials Science and Engineering Stanford UniversityStanfordCA 94305USA Department of Electrical and Computer Engineering Northwestern UniversityEvanstonIL 60208USA Department of Materials Science and Engineering Texas A&M UniversityTexasTX 77843USA joint Institute for Computational Sciences University of TennesseeKnoxvilleTN 37996USA National Institute for Computational Sciences Oak Ridge National LaboratoryOak RidgeTN 37831USA School for Engineering of Matter Transport and Energy Arizona State UniversityTempeAZ 85287USA Center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTN 37831USA Materials Science and Technology Division Los Alamos National LabLos AlamosNM 87545USA Department of Mechanical Engineering Virginia TechBlacksburgVA 24061USA Department of Physics and Astronomy Rutgers UniversityPiscatawayNJ 08901USA

The joint Automated Repository for Various Integrated Simulations(jARVIS)is an integrated infrastructure to accelerate materials discovery and design using density functional theory(DFT),classical force-fields(FF),and machine learning(ML)*** is motivated by the Materials Genome Initiative(MGI)principles of developing open-access databases and tools to reduce the cost and development time of materials discovery,optimization,and deployment.

关键词： automated jAR databases

Objective screening for olfactory and gustatory dysfunction during the COVID-19 pandemic: A prospective study in healthcare workers using self-administered testing

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World journal of Otorhinolaryngology-Head and Neck Surgery 2022年第3期8卷 249-256页

作者： Austin C.Cao zachary M.Nimmo Natasha Mirza Noam A.Cohen Robert M.Brody Richard L.Doty Perelman School of Medicine University of PennsylvaniaPhiladelphiaPAUSA Department of Otorhinolaryngology-Head and Neck Surgery University of PennsylvaniaPhiladelphiaPAUSA Corporal Michael j.Crescenz Veterans Administration Medical Center PhiladelphiaPAUSA Monell Chemical Senses Center PhiladelphiaPAUSA

Background: Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory ***: The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare ***: Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were ***: Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (jects. There was a time-dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR ***: Healthcare workers with recent SARS-CoV-2 infection had reduced olfaction and normal gustation on self-administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.

关键词： Anosmia Brief Smell Identification Test Chemosensory dysfunction COVID-19 Dysgeusia Gustation Healthcare workers Objective testing Olfaction Screening University of Pennsylvania Smell Identification Test

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为人类健康服务的光学技术

国际人才交流 2021年第11期 61-66页

作者： [美]储扎克杨云舟(译) 中国科学技术大学

什么是科学研究?科学研究有其遵循的一定流程。首先,我们需要提出一个想法来构成初步的假设;其次,我们需要制定一个研究方案来验证假设,精心设计并开展试验;最后,通过分析试验得出的数据,我们能够揭示最初的假设是否正确。如果假设错误... 详细信息

什么是科学研究?科学研究有其遵循的一定流程。首先,我们需要提出一个想法来构成初步的假设;其次,我们需要制定一个研究方案来验证假设,精心设计并开展试验;最后,通过分析试验得出的数据,我们能够揭示最初的假设是否正确。如果假设错误,我们就必须回到第一步,修改假设,进行“再研究”,再将流程循环到底。其实,科学研究的方法可以越过纯粹科学的边界,应用到生活中的许多方面。它实际上是帮助我们应对和解决生活难题的一个视角。正因如此,我们发现,有着严谨诚实的态度并且秉持以公众利益为重的科学,掌握着世间所有问题的答案,也拥有能够改变世界的力量。

关键词：验证假设科学研究光学技术分析试验公众利益人类健康纯粹科学生活