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Neural lineage differentiation of human pluripotent stem cells:Advances in disease modeling

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World Journal of Stem Cells 2023年第6期15卷 530-545页

作者： Yuan-Wei Yan Eddie S Qian Lauren E Woodard julie Bejoy Waisman Center University of Wisconsin-MadisonMadisonWI 53705United States Nephrology and Hypertension Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37232United States Department of Veterans Affairs Tennessee Valley Healthcare SystemNashvilleTN 37232United States Biomedical Engineering Vanderbilt UniversityNashvilleTN 37232United States

Brain diseases affect 1 in 6 people *** diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer’s *** advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models,tissue culture models,and epidemiologic patient data that are commonly used to study brain *** innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells(hPSCs)to neural lineages including neurons,astrocytes,and ***-dimensional models such as brain organoids have also been derived from hPSCs,offering more physiological relevance due to their incorporation of various cell *** such,brain organoids can better model the pathophysiology of neural diseases observed in *** this review,we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models.

关键词： Induced pluripotent stem cells Astrocytes Oligodendrocytes Microglia Brain organoids Assembloids

Effects of obesity on breast size,thoracic spine structure and function,upper torso musculoskeletal pain and physical activity in women

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Journal of Sport and Health Science 2020年第2期9卷 140-148页

作者： julie R.Steele Celeste E.Coltman Deirdre E.McGhee Biomechanics Research Laboratory School of MedicineUniversity of WollongongWollongongNSW 2522Australia Research Institute for Sport and Exercise Faculty of HealthUniversity of CanberraCanberraACT 2601Australia

Purpose:This study investigated the effects of obesity on breast size,thoracic spine structure and function,upper torso musculoskeletal pain and physical activity participation in women living independently in the ***:A total of 378 women were divided into 3 groups(Not Overweight:body mass index(BMI)=22.5±0.2 kg/m^2(mean±SE);Overweight:BMI=27.4±0.3 kg/m^2;Obese:BMI=35.4±0.3 kg/m^2).Outcome variables of breast volume(mL),thoracic flexion torque(N·m),thoracic kyphosis(degrees),upper torso musculoskeletal pain(score) and time spent in physical activity(min) were calculated and compared among the 3 groups,adjusting for between-group differences in ***:There was a significant main effect of BMI on all outcome *** classified as Obese displayed significantly larger breasts,had greater thoracic flexion torques and reported less time participating in physical activity relative to the participants who were classified as Not Overweight and *** in the Obese group also displayed significantly more thoracic kyphosis and reported significantly more upper torso musculoskeletal pain compared to their counterparts who were classified as Not ***:This study is the first to demonstrate that increased obesity levels were associated with compromised kyphosis and loading of the thoracic spine,as well as increased symptoms of upper torso musculoskeletal pain and reduced time spent in physical activity in women living in the *** recommend further research to determine whether evidence-based interventions designed to reduce the flexion torque generated on the thoracic spine can improve these symptoms of upper torso musculoskeletal pain and the ability of women with obesity to participate in physical activity.

关键词： Breast volume Obesity Thoracic kyphosis Upper torso loading

Habitual physical activity levels and sedentary time of children in different childcare arrangements from a nationally representative sample of Canadian preschoolers

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Journal of Sport and Health Science 2020年第6期9卷 657-663页

作者： julie Statler Piotr Wilk Brian W.Timmons Rachel Colley Patricia Tucker Faculty of Health Sciences University of Western OntarioLondonOntarioN6A 3K7Canada Schulich School of Medicine&Dentistry University of Western OntarioLondonOntarioN6A 3K7Canada Department of Pediatrics McMaster UniversityHamiltonOntarioL8S 4L8Canada Division of Health Analysis Statistics CanadaOttawaOntarioK1A 0T6Canada School of Occupational Therapy University of Western OntarioLondonOntarioN6A 3K7Canada

Background:Children spend substantial time in childcare,and the reasons parents choose a particular childcare type may differ by ***,little is known about how childcare type influences habitual(full day)activity levels among ***,exploring patterns between childcare type and habitual physical activity(PA)(i.e.,light,moderate-to-vigorous PA(MVPA),and total PA)and sedentary time(ST)in young Canadian children is ***:A nationally representative sample of preschoolers from Cycles 3 and 4 of the Canadian Health Measures Survey was used in this cross-sectional *** type(e.g.,center-based childcare,home-based childcare,home with parent,kindergarten)was reported by *** wore an Actical accelerometer for 7 *** and population-spcific cut-points were applied to delineate PA intensities and *** means and sample totals were calculated to examine average daily and hourly rates of ***:Preschoolers’rates of MVPA and total PA from the 4 childcare arrangements ranged from 65.99 min/day to 74.62 min/day(5.48-6.18 min/h)and 274.20 min/day to 281.66 min/day (22.69-23.21 min/h),respectively,while ST ranged from 443.13 min/day to 460.57 min/day(36.80-37.31 min/h).No significant differences were observed in daily or hourly rates of ***:This study provides a snapshot of the levels of PA and ST among preschoolers in various childcare settings at a national level,with no differences observed in habitual activity levels based on childcare *** research is needed to clarify the relationship between young children’s PA and childcare type,with consideration given to the quality of the childcare settings.

关键词： Early learning environment Motor activity Preschool Screen time

IGF1-PI3K-induced physiological cardiac hypertrophy:Implications for new heart failure therapies,biomarkers,and predicting cardiotoxicity

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Journal of Sport and Health Science 2021年第6期10卷 637-647,I0001页

作者： Sebastian Bass-Stringer Celeste M.K.Tai julie R.McMullen Baker Heart and Diabetes Institute MelbourneVIC 3004Australia Department of Physiology Anatomy and MicrobiologyLa Trobe UniversityBundooraVIC 3086Australia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourneVIC 3004Australia Department of Physiology and Department of Medicine Alfred Hospital Monash UniversityMelbourneVIC 3004Australia

Heart failure represents the end point of a variety of cardiovascular *** is a growing health burden and a leading cause of death *** date,limited treatment options exist for the treatment of heart failure,but exercise has been well-established as one of the few safe and effective interventions,leading to improved outcomes in ***,a lack of patient adherence remains a significant barrier in the implementation of exercise-based therapy for the treatment of heart *** insulin-like growth factor 1(IGF1)phosphoinositide 3-kinase(PI3K)pathway has been recognized as perhaps the most critical pathway for mediating exercisedinduced heart growth and ***,we discuss how modulating activity of the IGF1PI3K pathway may be a valuable approach for the development of therapies that mimic the protective effects of exercise on the *** outline some of the promising approaches being investigated that utilize PI3K-based therapy for the treatment of heart *** discuss the implications for cardiac pathology and cardiotoxicity that arise in a setting of reduced PI3K ***,we discuss the use of animal models of cardiac health and disease,and genetic mice with increased or decreased cardiac PI3K activity for the discovery of novel drug targets and biomarkers of cardiovascular disease.

关键词： Cardiac protection Cardiotoxicity Exercise Heart failure IGF1 PI3K Therapies

Flor Revisited(Again):eQTL and Mutational Analysis of NB-LRR Mediated Immunity to Powdery Mildew in Barley

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Journal of Integrative Agriculture 2014年第2期13卷 237-243页

作者： Roger Wise Priyanka Surana Greg Fuerst Ruo Xu Divya Mistry julie Dickerson Dan Nettleton Corn Insects and Crop Genetics Research Unit U.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Plant Pathology & Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Department of Statistics Iowa State UniversityAmesIowa 50011USA Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA

Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rarl （Required for Mla12-specified resistance1）, and Roml （Restoration of Mla-specified resistancel）. The HSP90-SGT1-RAR1 complex appears to function as chaperone in MLA-specified resistance, however, much remains to be discovered regarding the precise signaling underlying plant immunity. Genetic analyses of fast-neutron mutants derived from CI 16151 （Mla6） uncovered a novel locus, designated Rar3 （R_equired for Mla6-specified resitance3）. Rar3 segregates independent of Mla6 and Rarl, and rar3 mutants are susceptible to Blumeria graminis f. sp. hordei （Bgh） isolate 5874 （A VRar）, whereas, wild-type progenitor plants are resistant. Comparative expression analyses of the rar3 mutant vs. its wild-type progenitor were conducted via Barleyl GeneChip and GAIIx paired-end RNA-Seq. Whereas Rarl affects transcription of relatively few genes; Rar3 appears to influence thousands, notably in genes controlling ATP binding, catalytic activity, transcription, and phosphorylation; possibly membrane bound or in the nucleus, eQTL analysis of a segregating doubled haploid population identified over two-thousand genes as being regulated by Mla （q value/FDR=0.00001）, a subset of which are significant in Rar3 interactions. The intersection of datasets derived from mla-loss-of-function mutants, Mla-associated eQTL, and rar3-mediated transcriptome reprogramming are narrowing the focus on essential genes required for Mla-specified immunity.

关键词： eQTL transcript profiling immunity resistance signaling barley Blumeria graminis

SNAP23-Kif5 complex controls mGlu1 receptor trafficking

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Journal of Molecular Cell Biology 2018年第5期10卷 423-436页

作者： Fabrice Raynaud Vincent Homburger Martial Seveno Oana Vigy Enora Moutina Laurent Fagni julie Perroy IGF CNRS INSERM Univ. Montpel[ier F-34094 Montpellier France BioCampus Montpellier CNRS INSERM Univ. Montpellier F-34094 Montpellier France Present address: INSERM U1046 PhyMedExp CNRS UMR9214 Univ. Montpellier F-34094 Montpellier France

Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting. Here we investigated the nature of the molecular motor and adaptor protein responsible for trafficking and membrane localization of the group I metabotropic glutamate mGlu1 postsynaptic receptor in cultured hippocampal neurons. In proteomic studies, we identified the synaptosome-associated protein 23 （SNAP23） and the molecular motor Kif5 kinesin as proteins interacting with mGlu1 receptor. We showed that SNAP23, but not Kif5, directly interacts with mGlu1 receptor carboxyl terminus. Using a recombination approach to impair or enhance the interaction between SNAP23 and KifS, we found that the SNAP23-Kif5 complex controls the trafficking of mGlu1 receptor along microtubules. Additional fluorescence recovery after cleavage experiments allowed us to identify a role of the complex in the receptor cell surface targeting. In conclusion, our study indicates that along dendritic processes Kif5-SNAP23 complex contributes to proper mGlu1 receptor trafficking and cell surface expression.

关键词： mGlu1 SNARE kinesin neuron traffic

Prognostic value of chemotherapy-induced hematological toxicity in metastatic colorectal cancer patients

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World Journal of Gastroenterology 2014年第6期20卷 1565-1573页

作者： Laurie Rambach Aurelie Bertaut julie Vincent Veronique Lorgis Sylvain Ladoire Francois Ghiringhelli Department of Medical Oncology Centre Georges-Fran ois Leclerc Biostatistics and Epidemiological Unit EA4184 Centre Georges-Fran ois Leclerc Institut National de la Santé et de la Recherche Médicale (INSERM) CRI-866 Faculty of Medicine School of Medicine University of Burgundy

AIM: To establish whether chemotherapy-induced neutropenia is predictive of better outcome in patients with metastatic colorectal cancer (mCRC).

关键词： Colorectal cancer Metastasis Prognostic factor Neutropenia Chemotherapy

Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

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Bone Research 2014年第1期2卷 33-42页

作者： julie L Frey David P Stonko Marie-Claude Faugere Ryan C Riddle Department of Orthopaedic Surgery Johns Hopkins University School of Medicine Division of Nephrology Bone & Mineral Metabolism University of Kentucky Veterans Administration Medical Center

The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

关键词： PTH Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone Figure

Preparation and Control of the Formation of Single Core and Clustered Nanoparticles for Biomedical Applications Using a Versatile Amphiphilic Diblock Copolymer

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Nano Research 2010年第12期3卷 852-862页

作者： Hongwei Chen julie Yeh Liya Wang Hafsa Khurshid Nan Peng Andrew YWang Hui Mao Department of Radiology Center for Systems ImagingEmory University School of MedicineAtlantaGeorgia 30322USA Department of Physics and Astronomy University of DelawareNewarkDelaware 19716USA Department of Rehabilitation Medicine Chinese PLA General Hospital28 Fuxing RoadBeijing 100853China Ocean NanoTech LLC2143 Worth LaneSpringdaleArkansas 72764USA

We report the application of a versatile diblock copolymer,poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane)(PEO-b-PγMPS),to prepare nanocrystals such as iron oxide nanoparticles or quantum dots,with either a single core or multi-core cluster,for biomedical *** amphiphilic copolymer comprises both a hydrophilic PEO segment and a hydrophobic segment with a“surface anchoring moiety”(the silane group)which can interact effectively with the hydrophobic nanocrystals through ligand *** of the unique features of this work is that we can control the formation of either single core nanoparticles or multi-core nanoclusters by simply varying the conditions of ligand exchange and aging of the mixture of block copolymer and nanoparticles without needing to change the *** morphologies of the resulting single core nanoparticles or multi-core nanoclusters were confirmed by dynamic light scattering and transmission electron *** clustered nanoparticles exhibit enhanced physicochemical properties that are beyond those expected from a simple accumulation of individual ***,the hybrid nanoparticles containing both magnetic iron oxide nanoparticles and optical quantum dots obtained using our strategy provide have combined magnetic and optical functionalities that allow for potential new and expanded biomedical applications,as demonstrated by their use for magnetic resonance imaging and biomarker-targeted cell imaging.

关键词： Magnetic nanoparticles quantum dots nanoparticle coating copolymer multifunctional nanoparticles imaging