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rNA m^(6)A reader YTHDF2 facilitates precursor mir-126 maturation to promote acute myeloid leukemia progression

genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han andrew Small Jianhuang Xue Huilin Huang Hengyou Weng rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA gehr Family Center for Leukemia research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mrNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microrNAs(pri-mirNAs)and fa-cilitates its processing into precursor mirNAs(pre-mirNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-mirNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of mir-126-3p(also known as mir-126,as it is the main product of precursor mir-126(pre-mir-126)),a mirNA that was reported as an oncomirNA in AML,through facilitating the processing of pre-mir-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-mir-126 and recruits AgO2,a regulator of pre-mirNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with mir-126 and mir-126's downstream target genes,respec-tively,in AML patients,and forced expression of mir-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that mir-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/mir-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-mirNA processing that contributes to tumorigenesis.

关键词： AML mir-126 N^(6)-methyladenosine Pre-mirNA maturation YTHDF2

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Population structure and body condition of White-crested Elaenia(Elaenia albiceps)in relation to habitat in a modiffed Neotropical forest landscape

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Avian research 2023年第2期14卷 160-165页

作者： roberto F.Thomson andrew g.gosler Edward grey Institute of Field Ornithology Department of ZoologyUniversity of OxfordSouth Parks RoadOX13PSOxfordUK Laboratorio de Ecología de Vida Silvestre Facultad de Ciencias Forestales y Conservacion de la NaturalezaUniversidad de ChileSanta Rosa#11315La PintanaRegion MetropolitanaChile Institute of Human Sciences The Pauling Centre58a Banbury Rd.OxfordOX26QSUK

Despite the widely accepted view that planted forests are valuable habitat for wildlife species,there is a lack of empirical evidence showing the suitability of this novel habitat,especially in relation to plantations of exotic tree ***,little is known about the effects of forest management on the ecology and dynamics of wild populations in the *** the breeding season,the migrant flycatcher White-crested Elaenia is the most abundant bird species in forested landscapes in *** several years we have studied different aspects of these artificial forests in the coastal range of south-central Chile as habitat for the species,particularly in contrast to the native *** general,our results indicate that plantation forests offer a poorer quality habitat,where the density of the species tends to be lower than in the native forest,although a significant edge effect suggests that its quality can be mitigated by planting as a matrix mosaic with native ***,compared to native forests,populations in plantations contained a higher proportion of younger adult individuals maintaining larger territories,and showing poorer body *** suggest that these differences could also have an impact on the birds'longevity and survival.

关键词： Body condition Migrant planted forests Survival Temperate forests Territory

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Waterbird use of farm dams in south-eastern Australia:abundance and influence of biophysical and landscape characteristics

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Chinese Birds 2017年第1期8卷 12-24页

作者： andrew J.Hamilton ChloéConort Aurore Bueno Christopher g.Murray James r.grove Faculty of Veterinary and Agricultural Sciences The University of MelbourneDookie CampusCurrawaVIC 3647Australia Office of the Deputy Vice-Chancellor(research and Innovation) Federation University AustraliaBallaratVIC 3353Australia Department of rural Health Melbourne Medical School49 Graham StreetPO Box 6500SheppartonVIC 3632Australia École Nationale Supérieure Agronomique de Toulouse 31326 Castanet TolosanFrance Faculty of Science The University of MelbourneParkvilleVIC 3010Australia Faculty of Science Department of GeographyThe University of MelbourneParkvilleVIC 3010Australia

Background: While agriculture has taken much environmental water in Australia's Murray-Darling Basin, agricultural expansion has resulted in a vast number of farm dams, almost three-quarters of a million in the Murray-Darling Basin ***: Over a summer we studied(1) waterbird abundance and species richness and(2) the influence of biophysical and landscape characteristics across 49 farm dams at a large mixed-enterprise farm in northern Victoria on the southern reach of the Murray-Darling ***: On average, dams were found to host 27.1 ± 71.1 individuals/ha and 1.8 ± 2.9 species per pond. Such densities are comparable to those on natural wetlands. Dam surface area and perimeter and amount of vegetation were positively and strongly correlated with the rallidae density(birds/ha), but no other parameters were strongly correlated with any other functional group. The landscape in which the dams were embedded had a highly significant effect(p r of birds found on a ***: Our research needs to be complemented with further studies in other parts of the Basin and on other taxa, but given at our site they supported similar densities of individuals and species to natural wetlands, and given the fact that there are 710,539 farm dams in the Murray-Darling Basin, which hosts much of Australia's waterbird fauna, it is reasonable to suggest that farm dams are overlooked, and possibly very important, avian biodiversity hotspots. It also highlights the importance of a landscape setting, in which dams are situated, on the number of birds using the dams.

关键词： Farm ponds Waterbirds Waterfowl Zooplankton

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genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah g.Overbey Kirill grigorev Krista A.ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno andrew Boddicker Junhua Zhao Bryan Lajoie andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HrH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCr,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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CrISPr/Cas9 and genome Editing in Drosophila

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Journal of genetics and genomics 2014年第1期41卷 7-19页

作者： andrew r.Bassett Ji-Long Liu MrC Functional genomics Unit University of Oxford Department of Physiology Anatomy and Genetics

recent advances in our ability to design DNA binding factors with specificity for desired sequences have resulted in a revolution in genetic engineering, enabling directed changes to the genome to be made relatively easily. Traditional techniques for generating genetic mutations in most organisms have relied on selection from large pools of randomly induced mutations for those of particular interest, or time-consuming gene targeting by homologous recombination. Drosophila melanogaster has always been at the forefront of genetic analysis, and application of these new genome editing techniques to this organism will revolutionise our approach to performing analysis of gene function in the future. We discuss the recent techniques that apply the CrISPr/Cas9 system to Drosophila, highlight potential uses for this technology and speculate upon the future of genome engineering in this model organism.

关键词： Drosophila melanogaster CrISPr Cas9 genome engineering Targeted mutagenesis

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Classical epithelial-mesenchymal transition(EMT)and alternative cell death process-driven blebbishield metastaticwitch(BMW)pathways to cancer metastasis

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3388-3404页

作者： goodwin g.Jinesh andrew S.Broh Department of Molecular Oncology 12902 USF Magnolia DriveH.Lee Mofftt Cancer Center&Research InstituteTampa 33612 FLUSA Sarcoma Department 12902 USF Magnolia DriveH.Lee Mofftt Cancer Center&Research InstituteTampa33612FLUSA

Metastasis is a pivotal event that accelerates the prognosis of cancer patients towards *** that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for better *** this goal,we discuss the details of two distinct but overlapping pathways of metastasis:a classical reversible epithelial-to-mesenchymal transition(hybrid-EMT)-driven transport pathway and an alternative cell death process-driven blebbishield metastatic-witch(BMW)transport pathway involving reversible cell death *** knowledge about the EMT and BMW pathways is important for the therapy of metastatic cancers as these pathways confer drug resistance coupled to immune evasion/*** initiallydiscuss the EMT pathway and compare it with the BMW pathway in the contexts of coordinated oncogenic,metabolic,immunologic,and cell biological events that drive *** particular,we discuss how the cell death environment involving apoptosis,ferroptosis,necroptosis,and NETosis in BMW or EMT pathways recruits immune cells,fuses with it,migrates,permeabilizes vasculature,and settles at distant sites to establish ***,we discuss the therapeutic targets that are common to both EMT and BMW pathways.

关键词： metastasis metastatic transition

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Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

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World Journal of gastroenterology 2018年第43期24卷 4846-4861页

作者： andrew Mcguigan Paul Kelly richard C Turkington Claire Jones Helen g Coleman r Stephen McCain Centre for Cancer research and Cell Biology Queen’s University Belfast Department of Pathology Royal Victoria HospitalBelfast Department of Hepatobiliary Surgery Mater Hospital Centre for Public Health Queen’s University Belfast

This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to

关键词： Pancreatic cancer Pancreatic adenocarcinoma Pancreatic cancer risk factors Pancreatic cancer treatment

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Assessing feeding competition between lake whitefish Coregonus clupeaformis and round whitefish Prosopium cylindraceum

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Current Zoology 2010年第1期56卷 109-117页

作者： andrew MACPHErSON John A.HOLMES andrew M.MUIr David L.g.NOAKES Axelrod Institute of Ichthyology and Department of Zoology University of Guelph Faculty of Architecture Landscape and Design University of Toronto Pacific Biological Station Fisheries and Oceans Canada golder Associates Fisheries and Wildlife Department and Oregon Hatchery research Center Oregon State University

We collected lake whitefish Coregonus clupeaformis and round whitefish Prosopium cylindraceum from the main basin of Lake Huron and georgian Bay in the Laurentian great Lakes of North America to investigate details of diet and feeding tactics of these species in different seasons. Lake whitefish supports important commercial fisheries in Lake Huron and both species make use of habitats near the Bruce Nuclear Power Development, on the eastern shore of Lake Huron. Most fish of both species showed generalist feeding behavior, but some lake whitefish appeared to show specialist prey selection. The invasive spiny water flea Bythotrephes longimanus was an important component of the diet of both species. There was considerable dietary overlap between the whitefish species, but the ecological implications of these dietary overlaps are mitigated by the fact that dominant prey species differed in most seasons. We conclude that the potential for ecologically significant interactions between lake whitefish and round whitefish resulting from competition for similar benthic food resources in the main basin of Lake Huron is probably low [Current Zoology 56 （1）： 109-117, 2010].

关键词： Lake Huron Diet Feeding tactics Seasonal variation Invasive species

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Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

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World Journal of gastroenterology 2020年第23期26卷 3201-3212页

作者： andrew Eiterman Ali Lahooti Somashekar g Krishna Department of Internal Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of gastroenterology Hepatologyand NutritionThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

Pancreatic cancer has a high mortality rate with minimal proven *** Papillary Mucinous Neoplasms(IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies,successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia(high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include-through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

关键词： Pancreatic cyst Confocal endomicroscopy Microforceps biopsy Cyst fluid molecular analysis Endoscopic ultrasound Intraductal papillary mucinous neoplasms

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Confidence estimation in the prediction of epithermal neutron resonance self-shielding factors in irradiation samples using an ensemble neural network

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能源与人工智能(英文) 2022年第1期7卷 101-119页

作者： Ian M.Wilkinson ritwik r.Bhattacharjee Jenifer C.Shafer andrew g.Osborne Nuclear Science&Engineering The Colorado School of Mines101214th St.GoldenCO80401USA Department of Chemistry The Colorado School of Mines101214th St.GoldenCO80401USA Department of Mechanical Engineering The Colorado School of Mines1610 Illinois St.GoldenCO80401USA

Large neutron absorption resonances in the nuclides present in irradiation samples reduce the irradiating neutron flux at energies close to a *** neutron activation analysis of optically thick samples with resonant isotopes,this self-shielding effect can be significant,and must be accounted for to ensure accurate *** we show that an ensemble artificial neural network can be used to accurately predict the epithermal selfshielding factors in wires composed of up to 57 ***,the neural network can account for resonance interference that affects the self-shielding in samples containing nuclides with large overlapping *** use Monte Carlo simulations of sample wires irradiated in a thermal neutron spectrum to create the data for training the neural network and validate its predictions.A gaussian negative log likelihood loss function is combined with the ensemble to estimate the confidence in the predicted self-shielding factors when ground-truth data are unavailable.

关键词： Neutron activation analysis Epithermal self-shielding Neural Networks

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