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Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers

Translational Neurodegeneration 2020年第2期9卷 309-321页

作者： julia remnestål Linn Oijerstedt Abbe Ullgren Jennie Olofsson Sofia Bergström Kim Kultima Martin Ingelsson Lena Kilander Mathias Uhlén Anna Månberg Caroline Graff Peter Nilsson Division of Affinity Proteomics Department of Protein ScienceKTH Royal Institute of TechnologySciLifeLabTomtebodavägen 23 AAlpha 217165 SolnaStockholmSweden Swedish FTD Initiative StockholmSweden Division of Neurogeriatrics Centre for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164SolnaSweden Unit for hereditary dementias Theme AgingKarolinska University HospitalStockholmSweden Department of Medical Sciences Clinical ChemistryUppsala UniversityUppsalaSweden Department of Public Health and Caring Sciences GeriatricsUppsala UniversityUppsalaSweden Department of Neuroscience Karolinska InstitutetSolnaSweden

Background The clinical presentations of frontotemporal dementia(FTD)are diverse and overlap with other neurological *** are,as of today,no biomarkers in clinical practice for diagnosing the ***,we aimed to find protein markers in cerebrospinal fluid(CSF)from patients with FTD,presymptomatic mutation carriers and *** Antibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD(bvFTD,n=16)and progressive primary aphasia(PPA,n=13),as well as presymptomatic mutation carriers(PMC,n=16)and non-carriers(NC,n=8).A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF *** findings were further examined in an independent cohort including 13 FTD patients,79 patients with Alzheimer’s disease and 18 healthy *** We found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals(PMC and NC)for 26 *** analysis show patterns of separation between unaffected individuals and FTD patients,especially for those with a clinical diagnosis of *** most statistically significant differences in protein levels were found for VGF,TN-r,NPTXr,TMEM132D,PDYN and *** with FTD were found to have higher levels of TN-r and NF-M,and lower levels of VGF,NPTXr,TMEM132D and PDYN,compared to unaffected *** main findings were reproduced in the independent *** In this pilot study,we show a separation of FTD patients from unaffected individuals based on protein levels in *** investigation is required to explore the CSF profiles in larger cohorts,but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.

关键词： Frontotemporal dementia Cerebrospinal fluid Biomarkers Proteomics Antibody suspension bead array

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Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVr12

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World Journal of Gastroenterology 2016年第35期22卷 8050-8059页

作者： Christoph r Werner julia M Schwarz Daniel P Egetemeyr robert Beck Nisar P Malek Ulrich M Lauer Christoph P Berg Department of Gastroenterology Hepatology and Infectiology University Hospital Tübingen Institute of Medical Virology University Hospital Tübingen

AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVr) 12 wk after conclusion of treatment, and to determine predictors of SVr12 in this *** Two hundred and sixty patients treated with SOF combination partners Pr(n = 51), r(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets re ≥ 10 and 17/260 were postliver transplantation patients. 194/260 had HCV GT1, 44/260 HCV *** Two hundred and forty/256(93.7%) patients achieved SVr12(m ITT); 4/260 were lost to follow-up. SVr12 rates for subgroups were: 92% for SOF/DCV, 93% for each SOF/SMV, SOF/Pr, 94% for SOF/LDV, 100% for 3D, 94% for pretreated, 87% for liver cirrhosis, 82% for patients with platelets r transplantation, 95% for GT1 a, 93% for GT1 b, 90% for GT3, 100% for GT2, 4, and 6. 12 patients suffered from relapse, 6 prematurely discontinued treatment, of which 4 died. Negative predictors of SVr12 were a platelet count re ≥ 10(P r cirrhosis(P = 0.005) at baseline. In Interferonfree treatment GT3 had significantly lower SVr rates than GT1(P = 0.016). Side effects were mild. CONCLUSION Excellent SVr12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets re in special need for further research efforts to overcome comparatively higher rates of virological failure.

关键词： Sofosbuvir Simeprevir Ledipasvir 丙肝肝移植持续 virological 反应肝肝硬化副作用抵抗 Daclatasvir

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Effects of broccoli extract and various essential oils on intestinal and faecal microflora and on xenobiotic enzymes and the antioxidant system of piglets

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Open Journal of Animal Sciences 2012年第2期2卷 78-98页

作者： Kristin Mueller Nicole M. Blum Holger Kluge rolf Bauerfeind julia Froehlich Anneluise Mader Karola r. Wendler Andreas S. Mueller Delacon Biotechnik Ges.m.b.H. Steyregg Austria Institute of Agricultural and Nutritional Sciences Preventive Nutrition Group Martin Luther University of Halle-Wittenberg Halle Germany Institute of Animal Nutrition Free University of Berlin Berlin Germany Institute of Veterinary Hygiene and Infectious Diseases of Animals Justus Liebig University Giessen Giessen Germany

Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant derived substances that are discussed to improve the health of farm animals by direct and indirect antioxidant effects and by influencing microbial eubiosis in the gastrointestinal tract. Consequently our study aimed to investigate the influence of broccoli extract and the essential oils of tur- meric, oregano, thyme and rosemary, as selected individual additives, on intestinal and faecal microflora, on xenobiotic enzymes, and on the antioxidant system of piglets. Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8. The piglets were housed individually in stainless steel pens with slatted floor. The control group (Con) was fed a diet without an additive for 4 weeks. The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo), oregano (Oo), thyme (To) and rosemary (ro) were added to the diets of the remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’ key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The composition of bacterial microflora was examined by cultivating samples of jejeunal and colonic mucosa and of faeces under specific conditions. The mrNA expression of xenobiotic and antioxidant enzymes was determined by reversing transcrip- tase real time detection PCr (rT-PCr). Total antioxidant status was assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid peroxidation was determined by measuring thiobarbioturic acid reactive substances (TBA- rS). results: Compared to Con piglets all additives positively influenced weight gain and feed conversion in week 1. Over the whole trial period no significant differences in performance parameters existed between the experimental

关键词： Pigs Phytogenic Feed Additives Broccoli Extract Essential Oils Xenobiotic Enzymes Antioxidant System

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Efficient first-principles prediction of solid stability:Towards chemical accuracy

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npj Computational Materials 2018年第1期4卷 591-596页

作者： Yubo Zhang Daniil A.Kitchaev julia Yang Tina Chen Stephen T.Dacek rafael A.Sarmiento-Pérez Maguel A.L.Marques Haowei Peng Gerbrand Ceder John P.Perdew Jianwei Sun Department of Physics and Engineering Physics Tulane UniversityNew OrleansLA 70118USA Department of Materials Science and Engineering MITCambridgeMA 02139USA Materials Science Division LBNLBerkeleyCA 94720USA Department of Materials Science and Engineering UC BerkeleyBerkeleyCA 94720USA Institute of Physical Chemistry and National Center for Computational Design and Discovery of Novel Materials Department of ChemistryUniversity of BaselKlingelbergstrBasel 804056Switzerland Institut für Physik Martin-Luther-Universität Halle-WittenbergHalle D-06099Germany Department of Physics Temple UniversityPhiladelphiaPA 19122USA Department of Chemistry Temple UniversityPhiladelphiaPA 19122USA

The question of material stability is of fundamental importance to any analysis of system properties in condensed matter physics and materials *** ability to evaluate chemical stability,i.e.,whether a stoichiometry will persist in some chemical environment,and structure selection,*** crystal structure a stoichiometry will adopt,is critical to the prediction of materials synthesis,reactivity and ***,we demonstrate that density functional theory,with the recently developed strongly constrained and appropriately normed(SCAN)functional,has advanced to a point where both facets of the stability problem can be reliably and efficiently predicted for main group compounds,while transition metal compounds are improved but remain a *** therefore offers a robust model for a significant portion of the periodic table,presenting an opportunity for the development of novel materials and the study of fine phase transformations even in largely unexplored systems with little to no experimental data.

关键词： properties stability chemical

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Estimation of the carbon pool in soil and above-ground biomass within mangrove forests in Southeast Mexico using allometric equations

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Journal of Forestry research 2014年第1期25卷 129-134页

作者： Jesús Jaime Guerra-Santos rosa María Cerón-Bretón julia Griselda Cerón-Bretón Diana Lizett Damián-Hernández reyna Cristina Sánchez-Junco Emma del Carmen Guevara Carrió Centro de Investigación de Ciencias Ambientales-Universidad Autónoma del Carmen Av.Abasolo s/n.Col.Renovación 2da.Sección C.P.24180.Cd.del CarmenCampecheMéxico

We report the results of carbon stored in soil and aboveground biomass from the most important area of mangroves in Mexico, with dominant vegetation of red mangrove （rhizophora mangle L.）, Black mangrove （Avicennia germinans L.）, white mangrove （Laguncularia racemosa Gaertn.） and button mangrove （Conocarpus erectus L.）. We sampled soils with high fertility during the dry season in 2009 and 2010 at three sites on Atasta Peninsula, Campeche. We used allometric equations to estimate above ground biomass （AGB） of trees. AGB was higher in C. erectus （253.18±32.17 t？ha-1）, lower in A. germinans （161.93±12.63 t？ha-1）, and intermediate in r. mangle （181.70±16.58 t？ha-1） and L. racemosa （206.07±19.12 t？ha-1）. Of the three studied sites, the highest absolute value for AGB was 279.72 t？ha-1 in button mangrove forest at any single site. Carbon stored in soil at the three sites ranged from 36.80±10.27 to 235.77±66.11 t？ha-1. The Tukey test （p 〈0.05） made for AGB was higher for black mangrove showed significant differences in soil carbon content between black mangrove and button mangrove. C. erectus had higher AGB compared with the other species. A. germinans trees had lower AGB because they grew in hypersaline environments, which reduced their development. C. erectus grew on higher ground where soils were richer in nutrients. AGB tended to be low in areas near the sea and increased with distance from the coast. A. germinans usually grew on recently deposited sediments. We assumed that all sites have the same potential to store carbon in soil, and then we found that there were no significant differences in carbon content between the three samples sites： all sites had potential to store carbon for long periods. Carbon storage at the three sampling sites in the state of Campeche, Mexico, was higher than that reported for other locations.

关键词： carbon storage rhizophora mangle Laguncularia racemosa,Avicennia germinans tree biomass

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Gene variants of the phosphatidylcholine synthesis pathway do not contribute to rDS in the Chinese population

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World Journal of Pediatrics 2018年第1期14卷 52-56页

作者： Yu-Jun Chen julia Meyer Jennifer A.Wambach Kelcey DePass Daniel J.Wegner Xin Fan Qun-Yuan Zhang Heins Hillary F.Sessions Cole Aaron Hamvas Neonatology the First Affliated Hospital of GuangxiMedical UniversityNanningChina Division of Newborn Medicine Edward MallinckrodtDepartment of PediatricsWashington University Schoolof MedicineSt.LouisUSA

Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening Center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. results We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang popula-tions (0.0045 vs. 0.0064, respectively,P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous vari-ants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB;F341L was also not previously reported in exome sequencing project. Conclusions The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1,CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.

关键词： Genetic epidemiology Human population genetics Neonatal respiratory distress syndrome Pulmonary surfactant

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A clinically relevant combination treatment with doxorubicin and cyclophosphamide does not induce hepatotoxicity in C57BL/6J mice

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Liver research 2021年第4期5卷 239-242页

作者： Satyanarayana r Pondugula julia M Salamat Kodye L Abbott Patrick C Flannery Mohammed Majrashi Mohammed Almaghrabi Manoj Govindarajulu Sindhu ramesh Maninder Sandey Suneel K Onterue Chen-Che J Huang Yoshimi Iwaki Kristina Gill Natasha Narayanan Edwin McElroy Darshini Desai rishi Nadar Timothy Moore Muralikrishnan Dhanasekaran Department of Anatomy Physiology and PharmacologyCollege of Veterinary MedicineAuburn UniversityAuburnALUSA Department of Pharmacology Faculty of MedicineUniversity of JeddahJeddahSaudi Arabia Department of Drug Discovery and Development Harrison School of PharmacyAuburn UniversityAuburnALUSA Department of Pathobiology College of Veterinary MedicineAuburn UniversityAuburnALUSA Animal Biochemistry Division National Dairy Research InstituteICAR-National Dairy Research InstituteKarnalHaryanaIndia Department of Clinical Science College of Veterinary MedicineAuburn UniversityAuburnALUSA

Background and aims:Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity.A combination chemotherapy regimen of doxorubicin(DOX)and cyclophos-phamide(CPS)is employed in treatment of several cancers such as leukemia,lymphoma,and breast *** is not well understood whether a combination therapy with DOX and CPS can induce *** therefore sought to determine whether co-administration of DOX and CPS at their clini-cally relevant doses and frequency results in ***:Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 *** the treatment period,liver histology and various serum bio-markers of hepatotoxicity were ***:Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase(ALT),alkaline phosphatase(ALP),bilirubin,albumin,globulin,or total ***,co-administration of DOX and CPS did not result in a noticeable change in liver ***,it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase(AST).Elevated serum AST levels were also associated with increased serum creatinine kinase(CK)levels,suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and ***:Taken together,our results,for the first time,suggest that co-administration of DOX and CPS,at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.

关键词： Cyclophosphamide(CPS) Doxorubicin(DOX) Hepatotoxicity Liver injury Muscle injury

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脱乙酰甲壳质分子量对经其处理过的羊毛防缩性和染色性的影响

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国外纺织技术（纺织针织服装化纤染整） 2001年第1期 16-20页

作者： M.r.julia 郑敏沈煜如

1引言羊毛织物在含水或潮湿的环境中易毡缩是羊毛的天性之一.因此羊毛服装的防缩处理是相当必要的.在使用合成聚合物之前,传统的羊毛防缩处理方法是氧化,但这种处理增加了废水中AOX(可吸收的有机卤素化合物).因此,研究人员又接连开发了... 详细信息

1引言羊毛织物在含水或潮湿的环境中易毡缩是羊毛的天性之一.因此羊毛服装的防缩处理是相当必要的.在使用合成聚合物之前,传统的羊毛防缩处理方法是氧化,但这种处理增加了废水中AOX(可吸收的有机卤素化合物).因此,研究人员又接连开发了AOX防缩整理的各种新材料和新方法.

关键词：脱乙酰甲壳质分子量羊毛织物防缩处理染色性

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Use of Three Dimensional Conformal radiation Therapy for Node Positive Breast Cancer Does Not result in Excess Lung and Heart Irradiation

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International Journal of Medical Physics, Clinical Engineering and radiation Oncology 2017年第1期6卷 1-9页

作者： Phillip Prior Irina Sparks J. Frank Wilson Joseph Bovi Adam Currey Julie Bradley Tracy Kelly X. Allen Li julia r White Department of radiation Oncology Medical College of Wisconsin Milwaukee WI USA Department of radiation Oncology Ohio State University Columbus OH USA

Purpose: This work evaluates the use of target and organs at risk (OAr) dose-volume goals in 3D conformal radiotherapy (3DCrT) planning for node positive breast cancer (NPBC) patients undergoing regional nodal irradiation after lumpectomy/mastectomy. Methods: Dosimetric data for 262 NPBC patients receiving regional nodal and whole breast/chest wall (WB/CW) irradiation from 2000-2009 were analyzed. In all cases, target & OAr volumes were delineated on treatment CT scans for field generation and dose-volume histograms (DVHs) were generated. Cases were analyzed to identify how frequently they met treatment planning institutional dose-volume goals (“institutional guidelines” & standardized in 2005) and how this would affect OAr doses. results: The incidence of cases from 2000-2009 meeting current institutional guidelines improved over the study period. Target coverage improved from 2005-2009, when guidelines were followed as a part of the plan approval. Those cases from 2000-2004 meeting acceptable target goals were found to be significantly different from those cases from 2005-2009 (p r, no significant difference between cases meeting OAr goals for plans from 2000-2004 versus 2005-2009 was found. Conclusions: The use of institutional guidelines in 3DCrT for WB/CW and regional nodal irradiation for NPBC patients improved target coverage without a statistically significant increase in heart and lung doses.

关键词： Node Positive Breast Cancer Dose-Volume Goals Target Coverage CT Based Planning

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The role of extracellular vesicles in acquisition of resistance to therapy in glioblastomas

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Cancer Drug resistance 2021年第1期4卷 1-16页

作者： Anudeep Yekula Abigail Taylor Alexandra Beecroft Keiko M.Kang julia L.Small Koushik Muralidharan Zachary rosh Bob S.Carter Leonora Balaj Department of Neurosurgery Massachusetts General HospitalBostonMA 02114USA Brigham Young University ProvoUT 84602USA

Glioblastoma(GBM)is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking,followed by radiation therapy with concurrent and adjuvant temozolomide *** natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after *** mechanisms including inter-and intratumoral heterogeneity,the evolution of therapy-resistant clonal subpopulations,reacquisition of stemness in glioblastoma stem cells,multiple drug efflux mechanisms,the tumor-promoting microenvironment,metabolic adaptations,and enhanced repair of drug-induced DNA damage have been implicated in therapy *** vesicles(EVs)have emerged as crucial mediators in the maintenance and establishment of *** seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug *** include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based *** this review,we discuss the various mechanisms of therapy resistance in GBM,highlighting the emerging role of EV-orchestrated drug *** the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease.

关键词： Glioblastoma resistance extracellular vesicles temozolomide radiation

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