Accurate information on eye position in the orbit is available from visual feedback,efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM).Whereas visual feedback and o...Accurate information on eye position in the orbit is available from visual feedback,efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM).Whereas visual feedback and oculomotor commands have been extensively studied,central processing of EOM proprioceptive signals remains to be elucidated.A challenge to the field is to develop an approach to induce passive eye movements without physically contacting the eyes.A novel method was developed to generate passive eye movements in rats.A small rare-earth magnet disk (0.7 mm diameter,0.5 mm thickness) was attached to the surface of a rat's eyeball.A metal rod (5 mm diameter) wrapped with an electromagnetic (EM) coil was placed near the magnet (8-15 mm).By passing currents to the EM coil,electromagnetic force (EMF) was generated and acted upon the magnet and induced passive eye movements.The EMF induced well-defined passive eye movements,whose directions were dependent on current polarity and amplitudes and peak velocities were dependent on current intensity and duration.Peak velocities of the EMF-induced eye movements were linearly related to amplitudes,exhibiting main sequence relationships similar to that of saccades in awake rats and eye movements induced by electrical microstimulation of the abducens nucleus in anesthetized rats.Histological examination showed that repetitive EMF stimulations did not appear to result in damages in the EOM fibers.These results validated the EMF approach as a novel tool to investigate EOM proprioceptive signals and their roles in visual localization and gaze control.展开更多
Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved ove...Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.展开更多
Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved ove...Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.展开更多
基金supported by a Pre-doctoral Fellowship from the American Heart Association to ELS.(12PRE11530009)a Research Grant from the National Institute of Neurological Disorders and StrokeNational Institutes of Health,USA to DWB(NS050730)
基金supported by NIH grants to WZ(R21EY025550 R01DC014930)and HZ(R01DC012060)
文摘Accurate information on eye position in the orbit is available from visual feedback,efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM).Whereas visual feedback and oculomotor commands have been extensively studied,central processing of EOM proprioceptive signals remains to be elucidated.A challenge to the field is to develop an approach to induce passive eye movements without physically contacting the eyes.A novel method was developed to generate passive eye movements in rats.A small rare-earth magnet disk (0.7 mm diameter,0.5 mm thickness) was attached to the surface of a rat's eyeball.A metal rod (5 mm diameter) wrapped with an electromagnetic (EM) coil was placed near the magnet (8-15 mm).By passing currents to the EM coil,electromagnetic force (EMF) was generated and acted upon the magnet and induced passive eye movements.The EMF induced well-defined passive eye movements,whose directions were dependent on current polarity and amplitudes and peak velocities were dependent on current intensity and duration.Peak velocities of the EMF-induced eye movements were linearly related to amplitudes,exhibiting main sequence relationships similar to that of saccades in awake rats and eye movements induced by electrical microstimulation of the abducens nucleus in anesthetized rats.Histological examination showed that repetitive EMF stimulations did not appear to result in damages in the EOM fibers.These results validated the EMF approach as a novel tool to investigate EOM proprioceptive signals and their roles in visual localization and gaze control.
文摘Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.
文摘Acute myeloid leukemia(AML)is the most common form of acute leukemia in adults and the second most common form of acute leukemia in children.Despite this,very little improvement in survival rates has been achieved over the past few decades.This is partially due to the heterogeneity of AML and the need for more targeted therapeutics than the traditional cytotoxic chemotherapies that have been a mainstay in therapy for the past 50 years.In the past 20 years,research has been diversifying the approach to treating AML by investigating molecular pathways uniquely relevant to AML cell proliferation and survival.Here we review the development of novel therapeutics in targeting apoptosis,receptor tyrosine kinase(RTK)signaling,hedgehog(HH)pathway,mitochondrial function,DNA repair,and c-Myc signaling.There has been an impressive effort into better understanding the diversity of AML cell characteristics and here we highlight important preclinical studies that have supported therapeutic development and continue to promote new ways to target AML cells.In addition,we describe clinical investigations that have led to FDA approval of new targeted AML therapies and ongoing clinical trials of novel therapies targeting AML survival pathways.We also describe the complexity of targeting leukemia stem cells(LSCs)as an approach to addressing relapse and remission in AML and targetable pathways that are unique to LSC survival.This comprehensive review details what we currently understand about the signaling pathways that support AML cell survival and the exceptional ways in which we disrupt them.
