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Optogenetic inhibition of medial prefrontal cortex projections to the nucleus accumbens core and methyl supplementation via L-Methionine attenuates cocaine-primed reinstatement

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Integrative Zoology 2018年第6期13卷 795-803页

作者： Katherine N.WRIGHT Amanda M.DOSSAT Caroline E.STRONG lindsay L.SAILER Samantha M.PAVLOCK Mohamed KABBAJ Department of Biomedical Sciences and Program in Neuroscience Florida State UniversityTallahasseeFloridaUSA National Institute on Drug Abuse BaltimoreMarylandUSA Department of Biomedical Sciences College of MedicineFlorida State UniversityTallahasseeFloridaUSA

DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli,including exposure to drugs of ***,the medial prefrontal cortex(mPFC)projections to the nucleus accumbens(NAc)are critically important for reinstated cocaine-seeking in a rodent model of cocaine *** circuitry undergoes several epigenetic modifications following cocaine exposure,including changes in DNA methylation that are associated with drug-seeking *** have previously shown that methyl supplementation via L-Methionine(MET)administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos,suggesting that MET may act by altering the excitability of this circuitry during cocaine *** the current study,male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC,optical fibers were surgically implanted into the NAc,and the rats were given injections of MET *** underwent acquisition of cocaine self-administration(0.75 mg/kg/infusion,2-h sessions)followed by extinction training in the absence of drug-paired *** reinstatement tests were conducted:cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-NAc *** were no group differences before the cocaine-primed reinstatement session,and all groups showed robust cue-induced *** rats treated with MET and rats that received mPFC-to-NAc inhibition showed an abolishment of cocaine-primed reinstatement,suggesting that systemic methyl supplementation may act through this critical circuity.

关键词： cocaine-primed reinstatement corticolimbic DNA methylation methionine optogenetics

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A Simple Test of Seminal Fluid Chemistry and Its Potential Impact on Cryopreservation

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Open Journal of Veterinary Medicine 2023年第9期13卷 161-172页

作者： Glenn Yeomans lindsay Penrose Sam Prien Animal and Food Sciences Texas Tech University Lubbock USA Ob/Gyn Texas Tech University Health Sciences Center Lubbock USA

Cryopreservation is currently the only effective tool for long-term storage of semen in most species. However, it is well-recognized that, even in species that freeze well, some individuals resist cryopreservation. Work from this laboratory has demonstrated a relationship between maternal lipid content and the chemical constitution of the embryos they produce. The objective of the present study was to determine if a similar relationship might exist in paternal body chemistry and the animal’s semen sample and if such a difference could be determined with a simple weight test. Semen samples were obtained from cattle with known differences in body composition. The samples first underwent semen analysis and were then prepared as either cell-free (CF) or neat specimens (NS). Known volumes of each sample were weighed, and the remainder of the samples was analyzed for lipids, total proteins, and total carbohydrates using a series of spectrophotometric assays and blood chemistry techniques. As expected, weight differences were seen in the CF vs NS preparations of individual semen samples (p < 0.001). Differences were also found in triglycerides (p < 0.001), glucose (p < 0.001), total protein (p < 0.001), and fructose (p < 0.009) of individuals with differing body composition. Statistical analysis suggested a non-linear correlation between the observed weights and total protein (p < 0.047) as well as triglyceride levels (p < 0.003). Together, these data suggest it might be possible to develop an algorithm to allow adjustment in cryoprotectants based on a simple weight procedure, allowing modification of cryoprotectants on an individual basis and potentially improving outcomes for valuable animals currently classified as “poor freezers”.

关键词： Sperm Cryopreservation Customization Technique

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On-chip isotachophoresis separation of functional DNA origami capture nanoarrays from cell lysate

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Nano Research 2013年第10期6卷 712-719页

作者： Qian Mei Roger H. Johnson Xixi Wei Fengyu Su Yan Liu Laimonas Kelbauskas Stuart lindsay Deirdre R. Meldrum Hao Yan Center for Biosignatures Discovery Automation Arizona State University Tempe AZ 85287 USA Center for Single Molecule Biophysics Arizona State University Tempe AZ 85287 USA Department of Chemistryand Biochemistry Arizona State University Tempe AZ85287 USA Department of Physics Arizona State University Tempe AZ 85287 USA

Scaffolded DNA origami, a versatile method to construct high yield self- assembled DNA nanostructures, has been investigated to develop water-soluble nanoarrays for label free RNA detection, drug delivery, molecular positioning and recognition, and spatially ordered catalysis of single molecule chemical reactions. Its attributes that facilitate these applications suggest DNA origami as a candidate platform for intracellular targeting. After the interaction with targeted proteins in cell lysate, it is critical to separate and concentrate DNA origami nanoarrays from the crude cell lysate for further analysis. The recent development of microchip isotachophoresis （ITP） provides an alternative robust sample preconcentration and electrophoretic separation method. In this study, we present online ITP for stacking, separation and identification of aptamer-functionalized DNA origami and its thrombin complex in a simple cross-channel fused silica microfluidic chip. In particular, the method achieved separation of a binding complex in less than 5 min and 150-fold signal enhancement. We successfully separated and analyzed the thrombin bound origami-aptamer spiked into cell lysate using on-chip ITP. Our results demonstrate that origami/thrombin nanostructures can be effectively separated from cell lysate using this method and that the structural integrity of the concentrated binding complex is maintained as confirmed by atomic force microscopy （AFM）. An ITP-based separation module can be easily coupled to other microchip pre- and post-processing steps to provide an integrated proteomics analysis platform for diagnostic applications.

关键词： DNA origami nanoarray aptamer microfluidics isotachophoresis

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Summer Sunset Song

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小学生时代（大嘴英语） 2023年第6期 20-21页

作者： lindsay Koch April Dukes(图) 不详

Soft and cool under my feet,The grass gives way And I feel the summer heat Fade with the day.

关键词： Summer grass Sunset

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论科层方法评判学术能力所带来的问题

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上海大学学报（社会科学版） 2007年第1期14卷 29-33页

作者： lindsay Waters 张建琴哈佛大学出版社人文部美国马萨诸塞02138 上海大学外国语学院上海200444

在中国大学快速扩大的时期,应当重新审视学术创新的评估过程。西方大学模式受到推崇的原因是人们认为它可以带来创新和价值的创造。应更好地理解学术出版,尤其是著作和期刊论文的出版。论文提出了下列问题评估创造性是否有客观的方法?... 详细信息

在中国大学快速扩大的时期,应当重新审视学术创新的评估过程。西方大学模式受到推崇的原因是人们认为它可以带来创新和价值的创造。应更好地理解学术出版,尤其是著作和期刊论文的出版。论文提出了下列问题评估创造性是否有客观的方法?对出版物进行计数这一最简单最原始的评估创造性的方法究竟有多大价值?学者们应当关注学术出版物的内容而非数量。

关键词：大学创新评估创造性判断内容科层制

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B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia

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World Journal of Clinical Oncology 2020年第8期11卷 528-540页

作者： lindsay Wilde Sabarina Ramanathan Margaret Kasner Department of Hematology and Medical Oncology Sidney Kimmel Cancer Center at Thomas Jefferson University HospitalPhiladelphiaPA 19107United States

Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in recent ***,the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor *** given in combination with a hypomethylating agent or low dose cytarabine,venetoclax demonstrates high response rates,some of which are *** spite of this,relapses after venetoclax treatment are common,and much interest exists in elucidating the mechanisms of resistance to the *** in leukemic stem cell metabolism have been identified as a possible escape route,and clinical trials focusing on targeting metabolism in AML are *** review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism.

关键词： Acute myeloid leukemia B-cell lymphoma-2 Venetoclax Metabolism Leukemic stem cell Resistance

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Pragmatic language production deficits in Parkinson’s disease

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Advances in Parkinson's Disease 2013年第1期2卷 31-36页

作者： Thomas Holtgraves Kelly Fogle lindsay Marsh Department of Psychological Science Ball State University Muncie USA

This study examines pragmatic language production deficits in people with Parkinson’s disease (PD). Participants (PD and non-PD) were interviewed and their responses coded for degree of informativeness. PD participants weremore under-informative than non-PD participants. Response underinformativeness was associated with decreased executive control, mental status, and speech act comprehension measures. However, both speech act priming and utterance informativeness were strongly related to a measure of executive control, and when this variable (i.e., Stroop performance) was controlled, the correlation between speech act priming and utterance underinformativeness was no longer significant. It appears, then, that executive control deficits are related to the ability to comprehend and produce conversational utterances.

关键词： Pragmatic Deficits Parkinson’s Disease Conversation Maxims

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微量营养素食物强化指南

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作者： lindsay Allen[等]

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Plasma angiopoietin 2 as a novel prognostic biomarker in alcohol- related cirrhosis and hepatitis

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Liver Research 2022年第1期6卷 21-29页

作者： Victoria Tatiana Kronsten Josepmaria Argemi Ada Sera Kurt Godhev Mannakat Vijay Jennifer Marie Ryan Ramon Bataller Debbie lindsay Shawcross Institute of Liver Studies Department of Inflammation BiologySchool of Immunology and Microbial SciencesFaculty of Life Sciences and MedicineKing's College LondonUK Division of Gastroenterology Hepatology and NutritionPittsburgh Liver Research CenterUniversity of Pittsburgh Medical CenterPittsburghPAUSA Liver Unit.University of Navarra Clinic Hepatology Program.Center for Applied Medical Research(CIMA)Navarra Research InstitutePamplonaSpain Department of Hepatology Royal Free HospitalLondonUK

Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 *** angiopoietin-Tie 2 system regulates angiogenesis and inflammation,both of which are implicated in the pathogenesis of *** study examined plasma and hepatic gene expression of angiopoietin 1(ANG1)and angiopoietin 2(ANG2)in patients with SAH and ALD and investigated their roles as prognostic ***:A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay(ELISA)from 30 patients with SAH(Maddrey's discriminant function32),32 patients with ALD cirrhosis and 15 healthy controls(HC).RNA sequencing for ANG1,ANG2,TIE1(codes for Tie1 receptor)and TEK(codes for Tie2 receptor)gene expression from a separate cohort study of 79 patients was also ***:Plasma levels of ANG1 were lower(P=0.010)and ANG2 were higher(P<0.0001)in patients with ALD/SAH compared to *** ANG2:ANG1 ratio was higher in those with ALD/SAH compared to HC(P<0.0001).ANG2 levels were the highest in patients who developed sepsis(P=0.030)and those dying within 90 days(P=0.020).ANG2 levels correlated positively with model for end-stage liver disease(MELD)score(r=0.30,P=0.020),Child-Pugh score(r=0.38,P=0.003),international normalized ratio(r=0.41,P=0.001)and white blood cell count(r=0.28,P=0.040)and inversely correlated with albumin(r=0.26,P=0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC(P<0.0001),and greater in severe disease(P<0.0001).ANG2 gene expression trended towards being lower in SAH than that in HC(P=0.070)though was upregulated in severe disease(P=0.0003).Conclusions:Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.

关键词： Alcohol-related cirrhosis Alcoholic hepatitis Alcohol-related liver disease(ALD) Angiopoietin 1(ANG1) Angiopoietin 2(ANG2)

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E-Cigarette Vapor Decreases Cellular Proliferation through Nicotine-Dependent Mechanisms

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Journal of Biosciences and Medicines 2019年第7期7卷 121-134页

作者： Stefanie Rigg lindsay M. Gielda Purdue University Northwest Westville IN USA

Electronic cigarette (e-cigarette) use has risen as individuals look for healthier nicotine delivery systems than conventional cigarettes, but recent studies have demonstrated variable physiological responses to e-cigarette vapor. The safety of e-cigarette vapor remains an open question. We investigated the molecular cellular response of adenocarcinoma human alveolar basal epithelial (A549) cells to flavored e-cigarette vapor. E-cigarette and cigarette vapor were extracted via a vacuum-percolating system into PBS. The effects of a flavored e-liquid containing nicotine (eCSE) and nicotine free e-liquid (NFeCSE) were compared to cigarette smoke extract (CSE), pure nicotine, glycerol, and PBS. Cells exposed to eCSE and NFeCSE had decreased cell viability and proliferation. An increase in active caspase-3 was observed in cells exposed to NFeCSE, while cells exposed to eCSE and CSE displayed no change, suggesting nicotine-mediated protection from apoptosis. However, phosphorylated Akt, which regulates cellular proliferation, was elevated in response to eCSE, NFeCSE, CSE, and glycerol. As the glutathione-oxidative stress response was known to integrate cellular factors including carcinogenesis, inflammation, and cell proliferation, GSH/GSSG levels were measured in cells exposed to e-cigarette smoke. An increase in oxidative stress was observed in cells treated with CSE, but not eCSE, suggesting components in CSE independent of nicotine may be contributing to an imbalance in the stress response. These results indicate e-cigarette vapor affects A549 cell viability dependent on nicotine, and is distinct from CSE-induced mechanisms of oxidative-stress.

关键词： E-Cigarettes Oxidative Stress Nicotine Apoptosis

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