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Electrophysiology and heart rhythm disorders in older adults

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Journal of Geriatric Cardiology 2016年第8期13卷 645-651页

作者： Parag Goyal Michael W Rich Division of Cardiology Weill Cornell Medical College New York USA Cardiovascular Division Washington University School of Medicine St. Louis USA

Heart rhythm disorders, including bradyarrhythmias, atrial fibrillation (AF), and ventricular arrhythmias, become increasingly common with aging and represent important causes of morbidity and mortality among older adults. Older adults are particularly predisposed to these conditions due to the high prevalence of cardiovascular disease in conjunction with age-related changes that occur in the heart and cardiac conduction system.

关键词：心律不齐 Atrial 纤维性颤动 Bradycardia 变老室的心悸亢进

Die in pieces:How Drosophila sheds light on neurite degeneration and clearance

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Journal of Genetics and Genomics 2019年第4期46卷 187-199页

作者： Maria L.Sapar Chun Han weill Institute for Cell and Molecular Biology Department of Molecular Biology and GeneticsCornell University

Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate prior to neuronal death. Understanding the mechanisms of neurite degeneration has been an intense focus of neurobiology research in the last two decades. As a result, many discoveries have been made in the molecular pathways that lead to neurite degeneration and the cell-cell interactions responsible for the subsequent clearance of neuronal debris. Drosophila melanogaster has served as a prime in vivo model system for identifying and characterizing the key molecular players in neurite degeneration, thanks to its genetic tractability and easy access to its nervous system. The knowledge learned in the fly provided targets and fuel for studies in other model systems that have further enhanced our understanding of neurodegeneration. In this review, we will introduce the experimental systems developed in Drosophila to investigate injuryinduced neurite degeneration, and then discuss the biological pathways that drive degeneration. We will also cover what is known about the mechanisms of how phagocytes recognize and clear degenerating neurites, and how recent findings in this area enhance our understanding of neurodegenerative disease pathology.

关键词： Drosophila Neurite degeneration Axon Dendrite Wallerian degeneration Phagocyte Phagocytosis PS exposure Injury assay

Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids

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Journal of Molecular Cell Biology 2020年第8期12卷 580-592页

作者： Fong Cheng Pan Todd Evans Shuibing Chen Department of Surgery Weill Cornell Medical CollegeNew YorkNY 10065USA

Recent advances in development of protocols for directed differentiation from human pluripotent stem cells(hPSCs)to defined lineages,in combination with 3D organoid technology,have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated *** this review,we discuss current state-ofthe-art strategies for generating hPSC-derived endodermal organoids including stomach,liver,pancreatic,small intestine,and colonic *** also review the advantages of using this system to model various human diseases and evaluate the shortcomings of this ***,we emphasize how other technologies,such as genome editing and bioengineering,can be incorporated into the 3D hPSC-organoid models to generate even more robust and powerful platforms for understanding human organ development and disease modeling.

关键词： human pluripotent stem cells endoderm gastrointestinal development disease modeling

Dehydration and volume depletion:How to handle the misconceptions

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World Journal of Nephrology 2019年第1期8卷 23-32页

作者： Muhammad Asim Mohamad M Alkadi Hania Asim Adil Ghaffar Hamad General Hospital Hamad Medical Corporation and Weill Cornell Medicine-Qatar Birmingham City Hospital Dudley RoadBirmingham B18 7QHUnited Kingdom Saint Vincent Hospital

Dehydration and volume depletion describe two distinct body fluid deficit disorders with differing pathophysiology,clinical manifestations and treatment ***,the two are often confused or equated with each ***,we address a number of commonly encountered misconceptions about body-fluid deficit disorders,analyse their origins and propose approaches to overcome them.

关键词： Body fluids Dehydration Volume depletion Misconceptions

Detection and characterization of regulatory elements using probabilistic conditional random field and hidden Markov models

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Chinese Journal of Cancer 2013年第4期32卷 186-194页

作者： Hongyan Wang Xiaobo Zhou Department of Radiology the Methodist Hospital Research Institute Department of Radiology Weill Cornell Medical College

By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules, Chromatin marks have been proposed to regulate gene expression, a property that has motivated researchers to link these marks to cis-regulatory elements. With the help of next generation sequencing technologies, we can now correlate one specific chromatin mark with regulatory elements (e.g. enhancers or promoters) and also build tools, such as hidden Markov models, to gain insight into mark combinations. However, hidden Markov models have limitation for their character of generative models and assume that a current observation depends only on a current hidden state in the chain. Here, we employed two graphical probabilistic models, namely the linear conditional random field model and multivariate hidden Markov model, to mark gene regions with different states based on recurrent and spatially coherent character of these eight marks. Both models revealed chromatin states that may correspond to enhancers and promoters, transcribed regions, transcriptional elongation, and low-signal regions. We also found that the linear conditional random field model was more effective than the hidden Markov model in recognizing regulatory elements, such as promoter-, enhancer-, and transcriptional elongation-associated regions, which gives us a better choice.

关键词： Epigenetics, histone modification, conditional random field, regulatory elements

Non-enzymatic covalent modifications:a new link between metabolism and epigenetics

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Protein & Cell 2020年第6期11卷 401-416页

作者： Qingfei Zheng Igor Maksimovic Akhil Upad Yael David Chemical Biology Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Tri-Institutional PhD Program in Chemical Biology New YorkNY 10065USA Department of Pharmacology Weill Cornell MedicineNew YorkNY 10065USA Department of Physiology Biophysics and Systems BiologyWeill Cornell MedicineNew YorkNY 10065USA

Epigenetic modifications,including those on DNA and histones,have been shown to regulate cellular metabolism by controlling expression of enzymes involved in the corresponding metabolic *** turn,metabolic flux influences epigenetic regulation by affecting the biosynthetic balance of enzyme cofactors or donors for certain chromatin ***,non-enzymatic covalent modifications(NECMs)by chemically reactive metabolites have been reported to manipulate chromatin architecture and gene transcription through multiple ***,we summarize these recent advances in the identification and characterization of NECMs on nucleic acids,histones,and transcription factors,providing an additional mechanistic link between metabolism and epigenetics.

关键词： epigenetics metabolism non-enzymatic modification chromatin human disease

Long-term spaceflight and the cardiovascular system

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Precision Clinical medicine 2020年第4期3卷 284-291页

作者： Nicholas A.Vernice Cem Meydan Ebrahim Afshinnekoo Christopher E.Mason The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell Medicine1305 York AvenueNew YorkNY 10021USA Department of Physiology and Biophysics Weill Cornell Medicine1300 York AvenueNew YorkNY 10021USA The WordQuant Initiative for Quantitative Prediction Weill Cornell Medicine1300 York AvenueNew YorkNY 10021USA The Feil Family Brain and Mind Research Institute Weill Cornell Medicine1300 York Avenue New YorkNY 10021USA

While early investigations into the physiological effects of spaceflight suggest the body’s ability to reversibly adapt,the corresponding effects of long-term spaceflight(>6months)aremuch less *** exposure to microgravity and radiation yields profound effects on the cardiovascular system,including a massive cephalad fluid translocation and altered arterial pressure,which attenuate blood pressure regulatory mechanisms and increase cardiac ***,central venous pressure decreases as a result of the loss of venous *** stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15%reduction in plasma volume,with fluid translocating from the vascular lumen to the *** possible increases in cardiac workload,myocyte atrophy and notable,yet unexplained,alterations in hematocrit have been *** is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated *** data are scarce regarding their causative agents,arrhythmias have been frequently reported,albeit sublethal,during both Russian and American expeditions,with QT interval prolongation observed in long,but not short duration,*** of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration,aortic stiffness,carotid intima thickening via collagen-mediated action,accelerated atherosclerosis,and induction of a pro-inflammatory *** return,long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses,which can prove hazardous should any rapidmobilization or evacuation be required,and indicates that these cardiac risks should be especially monitored for future missions.

关键词： microgravity cardiovascular system spaceflight aerospace medicine

Exploring the role of anti-angiogenic therapies in prostate cancer： results from the phase 3 trial of sunitinib

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Asian Journal of Andrology 2014年第4期16卷 568-569页

作者： Himisha Beltran Gurveen Kaur Carmen Garcias de Espana Scott T Tagawa Division of Hematology and Medical Oncology Weill Cornell Medical College New York USA

Prostate cancer is aleading cause of cancer death in men. Despite recent advancesin our understanding and treatment of advanced disease, no systemic therapy is curative and new therapies are needed. Targeting angiogenesis is an attractive therapeutic strategy, as angiogenic pathways are upregulated in prostate tumors similar to other malignancies due to imbalance of pro- and anti-angiogenic factors secreted by tumor,

关键词： TYROSINE KINASE INHIBITOR SU11248 MEN

Oxytocin and cancer: An emerging link

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World Journal of Clinical Oncology 2018年第5期9卷 74-82页

作者： Ben Lerman Trisheena Harricharran Olorunseun O Ogunwobi Department of Biological Sciences Hunter College of the City University of New York the Graduate Center Departments of Biology and Biochemistry the City University of New York Joan and Sanford I. weill Department of medicine Weill Cornell Medicine Cornell University

The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.

关键词： Oxytocin Cancer Prostate Pancreas Exercise