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Molecular Plant 2019年第4期12卷 538-551页

作者： Vinay Shukla lara Lombardi Sergio lacopino Ales Pencik Ondrej Novak Pierdomenico Perata Beatrice Giuntoli Francesco Licausi Unstitute of Life Sciences Scuola Superiore Sant'Anna Pisa Italy Biology Department University of Pisa Pisa Italy Laboratory of Growth Regulators Centre of the Region Hana for Biotechnological and Agricultural Research Institute of Experimental Botany CAS & Faculty of Science. Palacky University Slechtitelu 27 78371 Olomouc Czech Republic

As non-photosynthesizing organs, roots are dependent on diffusion of oxygen from the external environment and, in some in stances, from the shoot for their aerobic metabolism . Establishment of hypoxic niches in the developing tissues of plants has been postulated as a consequence of insufficient diffusion of oxygen to satisfy the demands throughout development. Here, we report that such niches are established at specific stages of lateral root primordia development in Arabidopsis thaliana grown under aerobic conditions. Using gain- and loss-of-function mutants, we show that ERF-Ⅶ transcription factors, which mediate hypoxic responses, control root architecture by acting in cells with a high level of auxin signaling. ERF-Ⅶs repress the expression of the auxin-induced genes LBD16, LBD18, and PUCHI, which are essential for lateral root development, by binding to their promoters. Our results support a model in which the establishment of hypoxic n iches in the developing lateral root primordia con tributes to the shutting down of key auxin-induced genes and regulates the production of lateral roots.

关键词： Arabidopsis auxin ERF-VII, hypoxia lateral root root development

Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines

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Genomics, Proteomics & Bioinformatics 2021年第1期19卷 25-43页

作者： José Alexandre Ferreira Marta Relvas-Santos Andreia Peixoto AndréM.N.Silva Lúcio lara Santos Experimental Pathology and Therapeutics Group Portuguese Institute of OncologyPorto 4200-072Portugal Institute of Biomedical Sciences Abel Salazar University of PortoPorto 4050-313Portugal Porto Comprehensive Cancer Center(P.ccc) Porto 4200-072Portugal REQUIMTE-LAQV Department of Chemistry and BiochemistryFaculty of Sciences of the University of PortoPorto 4169-007Portugal

Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing(NGS),supported by robust *** quest for genomicsbased cancer medicine set the foundations for improved patient stratification,while unveiling a wide array of neoantigens for *** pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target ***,the low mutational burden presented by many lesions challenges the generalization of these solutions,requiring the diversification of neoantigen *** utilizing customized databases for protein annotation by mass spectrometry(MS)is a powerful tool toward this *** the concept toward exploring proteoforms originated from post-translational modifications(PTMs)will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer *** through the path of systems biology,we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted ***,we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics *** envisage that such rationale may flag a rather neglected research field,generating novel paradigms for precision oncology and immunotherapy.

关键词： Glycoproteogenomics Oncoproteogenomics Cancer neoantigens Glycosylation Precision oncology

C-type lectin receptor-induced NF-κB activation in innate immune and inflammatory responses

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Cellular & Molecular Immunology 2012年第2期9卷 105-112页

作者： lara M Kingeter Xin Lin Department of Molecular and Cellular Oncology The University of TexasM.D.Anderson Cancer CenterHoustonTXUSA Cancer Biology Program The University of TexasGraduate School of Biomedical SciencesHoustonTXUSA

The C-type lectin receptors （CLRs） belong to a large family of proteins that contain a carbohydrate recognition domain （CRD） and calcium binding sites on their extracellular domains. Recent studies indicate that many CLRs, such as Dectin-1, Dectin-2 and Mincle, function as pattern recognition receptors （PRRs） recognizing carbohydrate ligands from infected microorganisms. Upon ligand binding, these CLRs induce multiple signal transduction cascades through their own immunoreceptor tyrosine-based activation motifs （ITAMs） or interacting with ITAM-containing adaptor proteins such as FcRy. Emerging evidence indicate that CLR-induced signaling cascades lead to the activation of nuclear factor kappaB （NF-KB） family of transcriptional factors through a Syk- and CARD9-dependent pathway（s）. The activation of NF-κB plays a critical role in the induction of innate immune and inflammatory responses following microbial infection and tissue damages. In this review, we will summarize the recent progress on the signal transduction pathways induced by CLRs. and how these CLRs activate NF-κB and contribute to innate immune and inflammatory responses.

关键词： C-type lectin receptor innate immunity NF-κB

Polarized Defense Against Fungal Pathogens Is Mediated by the Jacalin-Related Lectin Domain of Modular Poaceae-Specific Proteins

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Molecular Plant 2016年第4期9卷 514-527页

作者： Denise Weidenbach lara Esch Claudia Moller Goetz Hensel Jochen Kumlehn Caroline Hofle Ralph Huckelhoven Ulrich Schaffrath Department of Plant Physiology RWTH Aachen University 52056 Aachen Germany plant Reproductive Biology Leibniz Institute of Plant Genetics and Crop Plant Research 06466 Stadt Seeland/OT Gatersleben Germany Center of Life and Food Sciences Weihenstephan Technische Universitat Munchen 85350 Freising Germany

Modular proteins are an evolutionary answer to optimize performance of proteins that physically interact with each other for functionality. Using a combination of genetic and biochemical experiments, we charac-terized the rice protein OsJAC1, which consists of a jacalin-related lectin （JRL） domain predicted to bind mannose-containing oligosaccharides, and a dirigent domain which might function in stereoselective coupling of monolignols. Transgenic overexpression of OsJAC1 in rice resulted in quantitative broad- spectrum resistance against different pathogens including bacteria, oomycetes, and fungi. Overexpression of this gene or its wheat ortholog TAJA1 in barley enhanced resistance against the powdery mildew fungus. Both protein domains of OsJAC1 are required to establish resistance as indicated by single or combined transient expression of individual domains. Expression of artificially separated and fluorescence-tagged protein domains showed that the JRL domain is sufficient for targeting the powdery mildew penetration site. Nevertheless, co-localization of the lectin and the dirigent domain occurred. Phylogenetic analyses re- vealed orthologs of OsJAC1 exclusively within the Poaceae plant family. Dicots, by contrast, only contain proteins with either JRL or dirigent domain（s）. Altogether, our results identify OsJAC1 as a representative of a novel type of resistance protein derived from a plant lineage-specific gene fusion event for better function in local pathogen defense.

关键词： jacalin-related lectin broad-spectrum disease resistance dirigent Rosetta stone protein rice (Oryza sativa) barley (Hordeum vulgare)

Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report

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World Journal of Gastrointestinal Oncology 2023年第10期15卷 1829-1834页

作者： Blake Buzard Lindsey Douglass Beth Gustafson Jennifer Buckley Marc Roth lara Kujtan Dhruv Bansal Cancer Institute St.Luke's HospitalKansasMO 64111United States Department of Medical Oncology University of Missouri-Kansas CityKansasMO 64108United States Department of Hematology/Oncology St.Luke's Cancer InstituteKansasMO 64111United States

BACKGROUND Although common in lung cancer,somatic epidermal growth factor receptor(EGFR)mutations are rarely found in colorectal cancer,occurring in approximately 3%of *** with anti-EGFR antibodies is commonplace,but EGFR tyrosine kinase inhibitors are not standard treatments in colorectal *** we report a case of sustained response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation on cell-free DNA *** SUMMARY A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair,scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic *** generation sequencing revealed a RAS/RAF wild-type,microsatellite stable,PD-L1 negative *** in TP3 and APC were also identified,as well as EGFR ***-free DNA analysis revealed an EGFR T790M *** was unable to tolerate first-line treatment with panitumumab,5-fluorouracil and leucovorin,progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab,and was unable to tolerate third-line treatment with *** was started on fourth-line treatment with off-label osimertinib,with clinical response–decrease in size of hepatic metastases and a pericardial *** remained on treatment with osimertinib for seven *** This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.

关键词： Colorectal cancer Osimertinib Epidermal growth factor receptor T790M Precision oncology Tyrosine kinase inhibitor Case report

Pigmented well-differentiated hepatocellular neoplasm with β-catenin mutation

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 660-664页

作者： lara Neves Souza Rodrigo Bronze de Martino Richard Thompson Sandra Strautnieks Nigel D Heaton Alberto Quaglia Institute of Liver Studies King's College Hospital Department of Gastroenterology Discipline of Liver and Gastrointestinal TransplantationHospital das ClínicasUniversity of S?o Paulo

ABSTRACT： According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the β-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcino- mas.

关键词： hepatocellular adenoma hepatocellular carcinoma β-catenin glutamine synthetase diethylstilbestrol

Comment on “Chen et al., Fabrication and photovoltaic conversion enhancement...”,Electrochimica Acta,2014

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Journal of Semiconductors 2015年第9期36卷 97-98页

作者： lara Valentic Nima E.Gorji Department of Environment Sciences,University of Nova Gorica Department of Physics,Brown University Department of Physics Brown University Providence 02912 Rhode Island USA

In a recent article, Chen et aL [Electrochimica Acta, 2014, 130： 279] presented their fabrication and characterization results on a graphene/n-Si solar cell where the Au nanoparticles were inserted in graphene to increase its optical and electrical properties. The higher efficiency of the device was attributed to increased conductivity of graphene after doping with Au nanoparticles. However, the knowledge in the field of Schottky diode solar cells relates this to increased band bending at the junction. Also, to explain the instability behaviour, they concluded that the growth of silicon oxide on the Si surface or oxygen adsorption on the window layer resulted in the device performance increasing initially and decreasing in the end. However, this instability seems to be due to variation in series resistance reduced at the beginning because of slightly lowered Fermi level and increased at the end by the self-compensation by deep in-diffusion ofAu nanoparticles into n-Si layer. We also propose that inserting a very thin p-type layer at the junction will enhance the carrier collection and performance of this device.

关键词： Shockley barrier solar cell graphene Si Au nanoparticle

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Journal of Sport and Health Science 2023年第3期12卷 414-422页

作者： Joseph M.Bano Rebecca J.McAdams Kristin J.Roberts Jingzhen Yang lara B.McKenzie Center for Injury Research and Policy Abigail Wexner Research Institute at Nationwide Children's HospitalColumbusOH 43205USA Department of Pediatrics The Ohio State UniversityCollege of MedicineColumbusOH 43205USA Division of Epidemiology The Ohio State UniversityCollege of Public HealthColumbusOH 43210USA

Background:Lacrosse is one of the fastest-growing sports in the United *** rules regarding permitted contact differ by sex and *** are no known studies using a nationally representative data set to analyze lacrosse injury patterns over several years by sex and age in the youth ***:A retrospective analysis was performed using data from the National Electronic Injury Surveillance System for youth aged 11-18 years who were treated for lacrosse-related injuries in *** departments from 2000 to *** on our review of the case narratives,we created and coded a new injury-mechanism *** generated national estimates from 6406 ***:An estimated 206,274 lacrosse-related injuries to youths aged 11-18 years were treated in *** departments from 2000 to *** rate of injuries per 10,000 significantly increased from 1.9 in 2000 to a peak of 5.3 in 2012(p<0.0001),followed by a significant decrease to 3.4 in 2016(p=0.020).Injury mechanism,body part injured,and diagnosis differed by *** were 1.62 times(95%confidence interval(95%CI):1.25-2.09)more likely than girls to be injured by player-to-player *** were 2.21 times(95%CI:1.96-2.49)more likely than boys to have non-contact ***,as age increased,the percentage of injuries from lacrosse sticks decreased and player-toplayer contact ***:Despite additional protective regulations in the sport,lacrosse is an important source of injury where we continue to see differences by sex and *** study supports the continuation,modification,and addition of rules aimed at reducing lacrosse injury risk.

关键词： Lacrosse National Electronic Injury Surveillance System Sex differences Youth injuries

Institutional experience of PTH evaluation on fine-needle washing after aspiration biopsy to locate hyperfunctioning parathyroid tissue

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第5期10卷 323-330页

作者： Massimo GIUSTI Mara DOLCINO lara VERA Carla GHIARA Francesca MASSARO Laura FAZZUOLI Diego FERONE Michele MUSSAP Francesco MINUTO Department of Endocrinology San Martino University Hospital Analysis Laboratory San Martino University Hospital

Assaying parathyroid hormone(PTH) in the washing liquid after fine-needle aspiration biopsy(FNAB) seems to be a valid approach to locate parathyroid ***-FNAB was evaluated in 47 patients with a clinical picture of primary hyper-parathyroidism(PHP) and ultrasonography(US) suggestive of parathyroid *** patients were subdivided into two groups on the basis of the absence or presence of US thyroid *** result of PTH-FNAB was compared with those of cytology,scintigraphy and,in 24 patients,surgical ***-FNAB samples with a value higher than that recorded in the serum and higher than our institutional cut-off were deemed to be probable samples of parathyroid *** proved diagnostic for benign thyroid lesions,non-diagnostic for thyroid lesions,hyperplastic parathyroid tissue,undetermined or malignant thyroid lesions and other lesions in 45%,30%,17%,4%,and 4% of cases,*** 47% of cases,PTH-FNAB indicated that the sample had been taken in parathyroid *** patients without US alterations,the diagnostic accuracy of PTH-FNAB was greater than that of *** surgery,comparison between the results of PTH-FNAB and scintigraphy,in terms of positive predictive value(PPV),revealed the superiority of PTH-FNAB;PPV was 94% for FNAB and 71% for scintigraphy,while sensitivity was 83% and 69%,***-FNAB evaluation after FNAB appears to be more diagnostic than cytology and *** all the procedures used,PTH-FNAB appears to be the method of choice when the target is US suggestive and ***-FNAB appears to be a useful method of guiding surgical intervention.

关键词： Primary hyperparathyroidism Nodular goitre Scintigraphy Ultrasonography Fine-needle aspiration biopsy (FNAB) Parathyroid hormone (PTH)-FNAB

DNA fragmentation in two cytometric sperm populations： relationship with clinical and ultrasound characteristics of the male genital tract

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Asian Journal of Andrology 2017年第3期19卷 272-279页

作者： Francesco Lotti lara Tamburrino Sara Marchiani Elisa Maseroli Pasquale Vitale Gianni Forti Monica Muratori Mario Maggi Elisabetta Baldi Sexual Medicine and Andrology Unit Department of Experimental and Clinical Biomedical Sciences Center of Excellence DeNothe University of FlorenceViale Pieraccini 6 1-50036 Florence Italy.

We investigated whether DNA fragmentation in two cytometric sperm populations （PIddimmer and PIbriehter） with different biological characteristics and clinical relevance is related to clinical and color-Doppler ultrasound （CDUS） parameters of the male genital tract. One hundred and sixty males of infertile couples without genetic abnormalities were evaluated for clinical, scrotal, and transrectal CDUS characteristics, presence of prostatitis-like symptoms （with the National Institutes of Health-Chronic Prostatitis Symptom Index） and sperm DNA fragmentation （sDF） in PIdimmer and PIbrighter populations （using TUNEIJPI method coupled with flow cytometry）. Data were adjusted for age （Model 1） along with waistline, testosterone levels, smoking habit, and sexual abstinence （Model 2）. According to the statistical Model 2, PIdi sDF was associated with testicular abnormalities, including lower clinical and ultrasound volume （r = -0.21 and r = -0.20, respectively; P 〈 0.05）, higher FSH levels （r = 0.34, P 〈 0.0001） and occurrence of testicular inhomogeneity （P 〈 0.05） and hypoechogenicity （P 〈 0.05）. PIbrighter sDF was associated with prostate-related symptoms and abnormal signs, including higher NIH-CPSI total and subdomain scores, a higher prevalence of prostatitis-like symptoms and of CDUS alterations such as macro-calcifications, severe echo-texture inhomogeneity, hyperemia （all P 〈 0.05）, and higher arterial peak systolic velocity （r = 0.25, P 〈 0.05）. Our results suggest that DNA fragmentation in PIdimmer sperm, which is related to poor semen quality, mainly originates in the testicles, likely due to apoptosis. Conversely, DNA fragmentation in PIbrighter sperm appears to mainly originate during or after transit through the prostate, increasing with the presence of an inflammatory status of the organ. These results could lead to new perspectives for the identification of therapeutic targets to reduce sDF.

关键词： color-Doppler ultrasonography DNA fragmentation male infertility male sex organs spermatozoa