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Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features

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science Bulletin 2020年第15期65卷 1281-1296,M0004页

作者： Xiangmin Lv Chunbo He Cong Huang Guohua Hua Xingcheng Chen Barbara K.Timm Victoria M.Maclin Abigail A.Haggerty shelly K.Aust Denae M.Golden Bhavana J.Dave Yun-An Tseng Li Chen Hongbo Wang Peichao Chen David L.Klinkebiel Adam R.Karpf Jixin Dong Ronny I.Drapkin Bo R.Rueda john s.davis Cheng Wang Vincent Center for Reproductive Biology Department of Obstetrics and GynecologyMassachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Olson Center for Women's Health Department of Obstetrics and GynecologyUniversity of Nebraska Medical CenterOmahaNE 68198USA College of Animal sciences and Veterinary Medicine Huazhong Agricultural UniversityWuhan 470000China Fred&Pamela Buffett Cancer Center University of Nebraska Medical CenterOmahaNE 68198USA Department of Pathology and Microbiology.University of Nebraska Medical Center OmahaNE 68198USA Heartland Center for Reproductive Medicine OmahaNE 68198USA Munroe-Meyer Institute University of Nebraska Medical CenterOmahaNE 68198USA Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China College of Life and Environmental science Wenzhou UniversityWenzhou 325035China Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNE 68198USA Department of Obstetrics and Gynecology University of PennsylvaniaPhiladelphiaPA 19104USA

Understanding the cell-of-origin of ovarian high grade serous cancer(HGsC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological ***,a mesenchymal type of ovarian HGsC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCs *** cell-of-origin of this subtype of ovarian cancer is *** pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous *** research results unveil a potential cell-of-origin for a subtype of HGsC with mesenchymal features.

关键词： Ovarian granulosa cells Cell reprogramming Cell dedifferentiation The Hippo pathway YAP1 oncogene Mesenchymal type of high grade serous cancer

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Why forefoot striking in minimal shoes might positively change the course of running injuries

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Journal of sport and Health science 2017年第2期6卷 154-161页

作者： Irene s.davis Hannah M.Rice scott C.Wearing spaulding National Running Center Department of Physical Medicine and Rehabilitation Harvard Medical School sport and Health sciences University of Exeter Institute of Health and Biomedical Innovation Queensland University of Technology

It is believed that human ancestors evolved the ability to run bipedally approximately 2 million years ago. This form of locomotion may have been important to our survival and likely has influenced the evolution of our body form. As our bodies have adapted to run, it seems unusual that up to 79% of modern day runners are injured annually. The etiology of these injuries is clearly multifactorial. However, 1 aspect of running that has significantly changed over the past 50 years is the footwear we use. Modern running shoes have become increasingly cushioned and supportive, and have changed the way we run. In particular, they have altered our footstrike pattern from a predominantly forefoot strike(FFs) landing to a predominantly rearfoot strike(RFs) landing. This change alters the way in which the body is loaded and may be contributing to the high rate of injuries runners experience while engaged in an activity for which they were adapted. In this paper, we will examine the benefits of barefoot running(typically an FFs pattern),and compare the lower extremity mechanics between FFs and RFs. The implications of these mechanical differences, in terms of injury, will be discussed. We will then provide evidence to support our contention that FFs provides an optimal mechanical environment for specific foot and ankle structures, such as the heel pad, the plantar fascia, and the Achilles tendon. The importance of footwear will then be addressed, highlighting its interaction with strike pattern on mechanics. This analysis will underscore why footwear matters when assessing mechanics. Finally, proper preparation and safe transition to an FFs pattern in minimal shoes will be emphasized. Through the discussion of the current literature, we will develop a justification for returning to running in the way for which we were adapted to reduce running-related injuries.

关键词： shoes running injuries strike predominantly landing tendon striking plantar locomotion

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Use of a handheld slit beam intraoperatively to assist in big bubble formation during deep anterior lamellar keratoplasty

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Annals of Eye science 2018年第1期3卷 369-374页

作者： Alexander s.davis Peter Bedard Joshua H.Hou Department of Ophthalmology and Visual Neurosciences University of MinnesotaMinneapolisMNUSA Dean McGee Eye Institute Oklahoma CityOKUSA Lions Gift of sight Eye Bank St.PaulMNUSA

Deep anterior lamellar keratoplasty(DALK)is preferred over conventional penetrating keratoplasty(PKP)for the treatment of anterior corneal opacities or ectasias due to decreased risk of endothelial ***,DALK remains surgically challenging,largely due to challenges associated with achieving consistent pneumo-dissection of posterior stroma from the underlying pre-Descemet’s or Descemet’s membrane(DM).Air must be injected at sufficient depth in the corneal stroma in order to achieve successful pneumo-dissection,but advancing a needle too deep into the cornea can lead to perforation of *** describe here a novel technique using a handheld slit lamp(Eidolon model 510L,Eidolon Optical LLC,Natick,MA,UsA)to assist in creation of the big-bubble in DALK *** of a handheld slit beam intraoperatively is a safe,relatively inexpensive,and effective technique for increasing the success of big-bubble formation in DALK procedures.

关键词： Deep anterior lamellar keratoplasty(DALK) big bubble technique slit beam

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Transition to forefoot strike reduces load rates more effectively than altered cadence

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Journal of sport and Health science 2020年第3期9卷 248-257页

作者： Erin E.Futrell K.Douglas Gross Darcy Reisman David R.Mullineaux Irene s.davis Department of Physical Therapy Springfield CollegeSpringfieldMA 01109USA spaulding National Running Center Harvard Medical SchoolCambridgeMA 02138USA Department of Physical Therapy MGH Institute of Health ProfessionsBostonMA 02129USA Department of Physical Therapy University of DelawareNewarkDE 19713USA school of sport and Exercise science University of LincolnBrayford PoolLincolnBrayford PoolLN67TSUK Department of Physical Medicine and Rehabilitation Harvard Medical SchoolBostonMA 02115USA

Background: Excessive vertical impacts at landing are associated with common running injuries. Two primary gait-retraining interventions aimed at reducing impact forces are transition to forefoot strike and increasing cadence. The objective of this study was to compare the shortand long-term effects of 2 gait-retraining interventions aimed at reducing landing ***: A total of 39 healthy recreational runners using a rearfoot strike and a cadence of 170 steps/min were randomized into cadence(CAD) or forefoot strike(FFs) groups. All participants performed 4 weeks of strengthening followed by 8 sessions of gait-retraining using auditory feedback. Vertical average load rates(VALR) and vertical instantaneous load rates(VILR) were calculated from the vertical ground reaction force curve. Both cadence and foot strike angle were measured using 3D motion analysis and an instrumented treadmill at baseline and at 1 week,1 month, and 6 months post ***: ANOVA revealed that the FFs group had significant reductions in VALR(49.7%) and VILR(41.7%), and changes were maintained long term. Foot strike angle in the FFs group changed from 14.2° dorsiflexion at baseline to 3.4° plantarflexion, with changes maintained long term. The CAD group exhibited significant reduction only in VALR(16%) and only at 6 months. Both groups had significant and similar increases in cadence at all follow-ups(CAD, +7.2% to 173 steps/min;and FFs, +6.1% to 172 steps/min).Conclusion: Forefoot strike gait-retraining resulted in significantly greater reductions in VALR and similar increases in cadence compared to cadence gait-retraining in the short and long term. Cadence gait-retraining resulted in small reductions in VALR at only the 6-month follow-up.

关键词： Foot strike Gait-retraining Physical therapy Running step rate

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Impact loading in female runners with single and multiple bone stress injuries during fresh and exerted conditions

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Journal of sport and Health science 2023年第3期12卷 406-413页

作者： Kristin L.Popp Jereme Outerleys sarah Gehman Margaret Garrahan sara Rudolph Elizabeth Loranger Kathryn E.Ackerman Adam s.Tenforde Mary L.Bouxsein Irene s.davis Military Performance Division United States Army Research Institute of Environmental MedicineNatickMA 01760USA Endocrine Unit Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Physical Medicine and Rehabilitation Spaulding Rehabilitation HospitalHarvard Medical SchoolCambridgeMA 02138USA Department of sports Medicine Boston Children's HospitalHarvard Medical SchoolBostonMA 02115USA Center for Advanced Orthopedic studies Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA

Background:Bone stress injuries(BsIs)are common in female runners,and recurrent BsI rates are *** work suggests an association between higher impact loading during running and tibial ***,it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple *** study compared impact variables at the beginning of a treadmill run to exertion andthe changes in those variables with exertion among female runners with no history of BsI as well as among those with a history of single or multiple ***:We enrolled 45 female runners(aged 18-40 years)for this cross-sectional study:having no history of diagnosed lower extremity BsI(N-BsI,n=14);a history of 1 lower extremity BsI(1-BsI,n=16);and diagnosed by imaging,or a history of multiple(>3)lower extremity BsIs(M-BsI,n=15).Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement *** vertical average loading rate(VALR),vertical instantaneous loading rate(VILR),vertical stiffness during impact via instrumented treadmill,and tibial shock determined as the peak po sitive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the ***:There were no differences between groups in VALR,VILR,vertical stiffness,or tibial shock in a fresh or exerted ***,compared to N-BsI,women with M-BsI had greater increase with exertion in VALR(-1.8%vs.6.1%,p=0.01)and VILR(1.5%vs.4.8%,p=0.03).similarly,compared to N-BsI,vertical stiffness increased more with exertion among women with M-BsI(-0.9%vs.7.3%,p=0.006)and 1-BsI(-0.9%vs.1.8%,p=0.05).Finally,compared to N-BsI,the increase in tibial shock from fresh to exerted condition was greater among women with M-BsI(0.9%vs.5.5%,p=0.03)and 1-BsI(0.9%vs.11.2%,p=0.02).Conclusion:Women with 1-BsI or M-BsIs experience greater exertion-related increases in impact loading than women with *** observations impl

关键词： Biomechanics Bone stress injuries Fatigue Runners stress fracture

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Targeting TrkB–PsD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Berrimach病毒免疫奶牛的研究

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中国畜禽传染病 1995年第5期17卷 25-28页

作者：张自刚 s.davis 中国农科院哈兽研所澳大利亚长袋试验室

Berrimacb病毒(BERV)是牛流行热病毒(BEFV)的相关病毒。它对牛仅表现为亚临床感染,在血清学上与BEPV存在交叉反应。以纯化BERV与Quil A佐剂配成免疫制剂接种奶牛后,取得了良好的免疫效果。

关键词：牛病乳牛流行热病毒疫苗免疫

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Reduction in ground reaction force variables with instructed barefoot running

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Journal of sport and Health science 2014年第2期3卷 143-153,157页

作者： Cynthia D.samaan Michael J.Rainbow Irene s.davis spaulding National Running Center Department of Physical Medicine and RehabilitationHarvard Medical School

Backgound:Barefoot(BF) running has recently increased in popularity with claims that it is more natural and may result in fewer injuries due to a reduction in impact ***,novice BF runners do not necessarily immediately switch to a forefoot strike *** may increase mechanical parameters such as loading rate,which has heen associated with certain running-related injuries,specifically,tibial stress *** pain,and plantar *** purpose of this study was to examine changes in loading parameters between typical shod running and instructed BF running with real-time force ***:Forty-nine patients seeking treatment for a lower extremity injury ran on a force-sensing treadmill in their typical shod condition and then BF at the same *** BF they received verbal instruction and real-time feedback of vertical ground reaction ***:While 92%of subjects(n = 45) demonstrated a rearfoot strike pattern when shod,only 2%(n = 1) did during the instructed BF ***,while BF 47%(n = 23) eliminated the vertical impact transient in all eight steps *** loading variables of interest were significantly reduced from the shod to instructed BF *** included maximum instantaneous and average vertical loading rates of the ground reaction force(p stiffness during initial loading(p s and impulses in the vertical(p s impact loading has been associated with certain running-related injuries,instruction and feedback on the proper forefoot strike pattern may help reduce the injury risk associated with transitioning to BF running.

关键词： Barefoot running Ground reaction force Loading rates Mediolateral forces Vertical stiffness

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Electrical stimulation and denervated muscles after spinal cord injury

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Neural Regeneration Research 2020年第8期15卷 1397-1407页

作者： subhalakshmi Chandrasekaran john davis Ines Bersch Gary Goldberg Ashraf s.Gorgey spinal Cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA swiss Paraplegic Centre NottwilSwitzerland Institute of Clinical sciences Department of Orthopedics at the University of GothenburgGothenburgSweden Department of Physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA Electrodiagnostic Center Hunter Holmes McGuire VA Medical CenterRichmondVAUSA

spinal cord injury(sCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous *** morphological changes may put individuals with sCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and ***,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in sCI individuals with lower motor neuron ***,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following *** pulse width stimulation(LPWs)technique is an upcoming method of stimulating denervated *** primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated *** parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and *** use of electrical stimulation in animal and human models induces muscle *** in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle *** studies have shown similar outcomes,identifying the use of LPWs as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle ***,displaying promise is an effective future stimulation *** summary,LPWs is a novel stimulation technique for denervated muscles in humans with *** studies on LPWs of denervated muscles will help in translating

关键词： denervation DXA electrical stimulation LMN injury LPWs MRI spinal cord injury stimulation parameters

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用作药物载体的聚合物微球

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生物医学工程学杂志 1989年第3期6卷 226-230页

作者： stanley s.davis Lisbeth Illum 杨晓陆英国诺丁罕大学药学系

聚合物载体近年来,人们用聚合体系作为药物载体的兴趣日益浓厚。这些体系既可采用可溶性聚合物(与药物形成可生物降解的键),也可采用可生物降解的微球(药物结合于微球中)。概括说来,通常把用于药物输送的聚合物微球归类为胶体载体。

关键词：载体聚合物微球药物

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