Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because ...Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].展开更多
Rice is often grown as multiple seasons in one year,alternating between flooded and upland systems.A major constraint,introduced from the flooded system,is a plough pan that may decrease rooting depth and productivity...Rice is often grown as multiple seasons in one year,alternating between flooded and upland systems.A major constraint,introduced from the flooded system,is a plough pan that may decrease rooting depth and productivity of follow-on upland rice.Roots penetrating the plough pan under flooded rice system can leave a legacy of weaker root growth pathways.Deeper rooting rice cultivars could have a bigger impact,but no direct evidence is available.To explore whether a deep rather than a shallow rooting rice cultivar grown in a flooded cropping cycle benefited deeper root growth of follow-on rice in an upland,reduced tillage cropping cycle,a simulated flooded paddy in greenhouse was planted with deep(Black Gora) and shallow(IR64) rooting cultivars and a plant-free control.Artificial plough pans were made in between the topsoil and subsoil to form different treatments with no plough pan(0.35 MPa),soft plough pan(1.03 MPa) and hard plough pan(1.70 MPa).After harvest of this ‘first season’ rice,the soil was drained and undisturbed to simulate zero-tillage upland and planted rice cultivar BRRI Dhan 28.The overall root length density(RLD),root surface area,the numbers of root tips and branching of BRRI Dhan 28 did not vary between plough pan and no plough pan treatments.Compared with the shallow rooting rice genotype,the deep rooting rice genotype as ‘first season’ crop produced 19% greater RLD,34% greater surface area and 29% more branching of BRRI Dhan 28 in the subsoil.In the topsoil,however,BRRI Dhan 28 had 28% greater RLD,35% greater surface area and 43% more branching for the shallow rather than deep rooting genotype planted in the ‘first season’.The results suggested that rice cultivar selection for a paddy cycle affects root growth of a follow-on rice crop grown under no-till,with benefits to subsoil access from deep rooting cultivars and topsoil proliferation for shallow rooting cultivars.展开更多
Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to ...Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is mo展开更多
There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie th...There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.展开更多
Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cau...Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development.However,the cellular functions of Ddr2 in bone are not understood.Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum.Consistent with these findings,Ddr2^(+)cells could differentiate into hypertrophic chondrocytes,osteoblasts,and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker,Gli1.A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts.Furthermore,Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation,respectively.This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.展开更多
Photophobia is a common symptom seen in many neurologic disorders,however,its pathophysiology remains unclear.Even the term is ambiguous.In this paper,we review the epidemiology and clinical manifestations of photopho...Photophobia is a common symptom seen in many neurologic disorders,however,its pathophysiology remains unclear.Even the term is ambiguous.In this paper,we review the epidemiology and clinical manifestations of photophobia in neurological disorders,including primary headache,blepharospasm,progressive supranuclear palsy,and traumatic brain injury,discuss the definition,etiology and pathogenesis,and summarize practical methods of diagnosis and treatment.展开更多
Prevention The best treatment is to prevent the illness in the first place or to retard its progression. There is considerable new information about Parkinson's disease genetics and pathophysiology that hopefu... Prevention The best treatment is to prevent the illness in the first place or to retard its progression. There is considerable new information about Parkinson's disease genetics and pathophysiology that hopefully will lead to therapy in this regard, but there is still nothing definitive. The only medication for which there are some reasonable data is selegiline, a monoamine oxidase (MAO)-B inhibitor. This drug actually has a symptomatic effect since it prevents the breakdown ofdopamine in the brain. Some trials have shown a beneficial effect separate from its symptomatic effect. The situation is rather controversial, however, and in one study there was an excess of mortality. {4}There are no supportive data for antioxidants such as vitamin E, and a trial of the neurotrophic factor GDNF was not positive.
……展开更多
Background: Hazardous alcohol consumption and associated harms are high among young uni- versity students. The university environment is conducive to excessive alcohol consumption with studies finding young university...Background: Hazardous alcohol consumption and associated harms are high among young uni- versity students. The university environment is conducive to excessive alcohol consumption with studies finding young university students to drink alcohol at higher levels than their non-university peers. Methods: A random sample of 18 - 24-year-old undergraduate, internal university students completed a survey (n = 2465) to investigate differences in self-reported personal, second-hand and witnessed alcohol-related harms, alcohol expectancies, pre-loading, and friends’ alcohol consumption between low risk and hazardous drinkers. Univariate and multivariate analyses are reported. Results: Almost 40% of students who had consumed alcohol in the past year reported drinking at hazardous levels. Univariate analyses found students who reported hazardous drinking reported significantly higher scores relating to experienced, second-hand, witnessed and academic problems compared to low risk drinkers. Hazardous drinkers were also more likely to pre-load, to drink at higher levels when pre-loading, have more friends who drank alcohol, have more friends who drank at hazardous levels and to score higher on alcohol expectancies. However both low risk and hazardous drinkers experienced a range of harms due to their own drinking including hangover (71.2%), unprotected sex (19.3%), regretted sex (16.8%) and drink-driving (17%). Looking after an intoxicated student (34.3%) and witnessing someone pass out (37.5%) were issues for all drinkers. Experienced alcohol related harms, academic problems, alcohol expectancies, close friends’ level of alcohol consumption, pre-loading in the last four weeks and level of consumption when pre-loading were predictors of hazardous drinking (p < 0.001). Conclusion: Young undergraduate university students are at risk of a range of academic, social, emotional and physical harms associated with their own and other students’ alcohol consumption. There is a need for integrated programs to address university dr展开更多
Objective: To explore the role of abnormal neuronal activity in the basal gang lia and thalamus in the generation of dystonia. Methods: Microelectrode recordin g was performed in the globus pallidus internus (GPi), ve...Objective: To explore the role of abnormal neuronal activity in the basal gang lia and thalamus in the generation of dystonia. Methods: Microelectrode recordin g was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucl eus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) d uring surgery. Electromyogram (EMG) was simultaneously recorded in selected musc le groups. Single unit analysis and cross correlations were carried out. Result s: Three hundred and sixty seven neurons were obtained from 29 trajectories (GP i: 13; Vop/Vim:12; STN: 4), 87%exhibited altered neuronal activity including gr ouped discharges in GPi (n=79) and STN (n=37), long lasting neuronal activity ( n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EM G at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0. 64 (n=18) and STN: r2=0.86 (n=17)). Conclusions: Consistent with previous findin gs of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the pre sent data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the prod uction of dystonic movement. Dystonia related neuronal activity observed in mot or thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the developme nt of either generalized or focal dystonia. Significance: These data support a c entral role of the basal ganglia in producing dystonic movements.展开更多
Phagocytosis is a fundamental cell biological process exhibited by a wide variety of cell types from single cell organ-isms,which rely on this for feeding,to phagocytes in higher animals,which rely on specialised immu...Phagocytosis is a fundamental cell biological process exhibited by a wide variety of cell types from single cell organ-isms,which rely on this for feeding,to phagocytes in higher animals,which rely on specialised immune cells for com-bating infecting micro-organisms.In the immune system,both macrophages and neutrophils play roles as phagocytes.Neutrophils are often called'professional phagocytes'because of their remarkable capacity for phagocytosis,beingable to internalise microscopic particles(diam 0.5-3 μm)of virtually any surface material.The efficiency and speedof phagocytosis is,however,increased by coating the surface of the particles with opsonins such as antibodies or thecomplement component C3bi(acting on β2 integrin receptors),and C3bi-accelerated phagocytosis by neutrophils is thefirst line of defence by the innate immune system in vivo,operating in advance of the slower production of antibodies.Understanding the mechanism of phagocytosis is,therefore,clearly an important goal.展开更多
Background:Focal dystonia is a neurological disorder characterized by unwanted muscle spasms.Blepharospasm is a focal dystonia producing an involuntary closure of the eyelid.Its etiology is unknown.Objective:To invest...Background:Focal dystonia is a neurological disorder characterized by unwanted muscle spasms.Blepharospasm is a focal dystonia producing an involuntary closure of the eyelid.Its etiology is unknown.Objective:To investigate if there are structural changes in the white and grey matter of blepharospasm patients,and if the changes are related to disease features.Methods:T1 and diffusion-weighted magnetic resonance imaging scans were collected from 14 female blepharospasm patients and 14 healthy matched controls.Grey matter volumes,fractional anisotropy(FA),and mean diffusivity maps were compared between the groups.Based on grey matter differences within the facial portion of the primary motor cortex,the corticobulbar tract was traced and compared between groups.Results:Changes in grey matter in patients included the facial portion of the sensorimotor area and anterior cingulate gyrus.These changes did not correlate with disease duration.Corticobulbar tract volume and peak tract connectivity were decreased in patients compared with controls.There were no significant differences in FA or mean diffusivity between groups.Conclusions:Grey matter changes within the primary sensorimotor and the anterior cingulate cortices in blepharospasm patients may help explain involuntary eyelid closure and the abnormal sensations often reported in this condition.展开更多
Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,as well as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are ...Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,as well as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are still elusive.Greater understanding of NK cell biology,from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential of NK cells.Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands.The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells.Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,and provide superior graft-versus-tumor (GVT) responses.Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NK cells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologic malignancies.Cellular & Molecular Immunology.2004;1(1):12-21.展开更多
基金the National Natural Science Foundation of China(81520108016,81661148045,and 31471084 to Yu-Feng Zang81671774 and 81630031 to Chao-Gan Yan+11 种基金81571228 to Tao Wu61571047 to Xia Wu81701664 to Jian Wang,81471654 to Biao Huang81701671 to Wei-Guo Liu82001898 to Xi-Ze Jia81771820,81371519 and 81571654 to Wei Luo)Henry G Leong Endowed Professorship in Neurology to Shu-Leong Ho and Shirley YY Pang,BRC for Mental Health at South London and Maudsley NHS Foundation Trust and by the Sackler Institute to Grainne McAlonan,NIH(2R01AG006457 to Fay B.Horak1RC4NS073008-01 and P50NS062684 to Tara Madhyastha)NINDS Intramural Research Program to Mark HallettStart-up Funds for Leading Talents at Beijing Normal UniversityNational Basic Science Data Center‘‘Chinese Data-sharing Warehouse for In-vivo Imaging Brain”(NBSDC-DB-15)to Xi-Nian ZuoGrant NU20-04-00294 of the Agency for Health Research,Czech Republic to Lenka Krajcovicova and Irena Rektorova。
文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].
基金funded by the Commonwealth Scholarship Commission in the UK。
文摘Rice is often grown as multiple seasons in one year,alternating between flooded and upland systems.A major constraint,introduced from the flooded system,is a plough pan that may decrease rooting depth and productivity of follow-on upland rice.Roots penetrating the plough pan under flooded rice system can leave a legacy of weaker root growth pathways.Deeper rooting rice cultivars could have a bigger impact,but no direct evidence is available.To explore whether a deep rather than a shallow rooting rice cultivar grown in a flooded cropping cycle benefited deeper root growth of follow-on rice in an upland,reduced tillage cropping cycle,a simulated flooded paddy in greenhouse was planted with deep(Black Gora) and shallow(IR64) rooting cultivars and a plant-free control.Artificial plough pans were made in between the topsoil and subsoil to form different treatments with no plough pan(0.35 MPa),soft plough pan(1.03 MPa) and hard plough pan(1.70 MPa).After harvest of this ‘first season’ rice,the soil was drained and undisturbed to simulate zero-tillage upland and planted rice cultivar BRRI Dhan 28.The overall root length density(RLD),root surface area,the numbers of root tips and branching of BRRI Dhan 28 did not vary between plough pan and no plough pan treatments.Compared with the shallow rooting rice genotype,the deep rooting rice genotype as ‘first season’ crop produced 19% greater RLD,34% greater surface area and 29% more branching of BRRI Dhan 28 in the subsoil.In the topsoil,however,BRRI Dhan 28 had 28% greater RLD,35% greater surface area and 43% more branching for the shallow rather than deep rooting genotype planted in the ‘first season’.The results suggested that rice cultivar selection for a paddy cycle affects root growth of a follow-on rice crop grown under no-till,with benefits to subsoil access from deep rooting cultivars and topsoil proliferation for shallow rooting cultivars.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(No.81371256,81171061,81361128012)Ministry of Education of Republic of China(BIBD-PXM2013-014226-07-000084)Seed Grant of International Alliance of Translational Neuroscience(PXM2014-014226-000015).
文摘Background:The cardinal features of Parkinson’s disease(PD)are bradykinesia,rigidity and rest tremor.Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms.This study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.Methods:Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus(STN)DBS(n=11),unilateral pallidotomy(n=9)and unilateral thalamotomy(n=9)were studied.Microelectrode recordings in the STN,globus pallidus internus(GPi)and ventral oral posterior/ventral intermediate of thalamus(Vop/Vim)were performed.Electromyography of the contralateral limbs was recorded.Single unit characteristics including interspike intervals were analyzed.Spectral and coherence analyses were assessed.Mean spontaneous firing rate(MSFR)of neurons was calculated.Analysis of variance and χ^(2) test were performed.Results:Of 76 STN neurons,39.5% were 4–6 Hz band oscillatory neurons and 28.9% were β frequency band(βFB)oscillatory neurons.The MSFR was 44.2±7.6 Hz.Of 62 GPi neurons,37.1% were 4–6 Hz band oscillatory neurons and 27.4% were βFB neurons.The MSFR was 80.9±9.6 Hz.Of 44 Vop neurons,65.9% were 4–6 Hz band oscillatory neurons and 9%were βFB neurons.The MSFR was 24.4±4.2 Hz.Of 30 Vim oscillatory neurons,70% were 4–6 Hz band oscillatory neurons and 13.3% were β FB neurons.The MSFR was 30.3±3.6 Hz.Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim(P<0.05).Conversely,the proportion of 4–6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi(P<0.05).The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons(P<0.005).Conclusion:The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism.β oscillatory activity is mo
基金a National Health and Medical Research Council Leadership Fellowship(1195830)has received research funding from The Michael J.Fox Foundation and the Australian Research Council.S.A.F.was supported by The Sartain Lanier Family Foundation.He has been a consultant for Lundbeck,Sunovion,Biogen,Impel,Acorda,and CereSpir.He has received education and research grants from Medtronic,Boston Scientific,Sun Pharmaceuticals Advanced Research Company,Biohaven,Impax,Lilly,US World Meds,Sunovion Therapeutics,Neurocrine,Vaccinex,Voyager,Jazz Pharmaceuticals,CHDI Foundation,The Michael J.Fox Foundation,National Institutes of Health(NIH),and Parkinson’s Foundation.He receives royalties from Demos,Blackwell Futura,Springer for textbooks,and UpToDate.Other support was from Signant(Bracket Global LLC)and CNS Ratings LLC.N.G.serves as consultant to Sionara,NeuroDerm,Pharma2B,Denali,Neuron23,Sanofi-Genzyme,Biogen,and AbbVie.He receives royalties from Lysosomal Therapeutics(LTI)and payment for lectures at AbbVie,Sanofi-Genzyme,and Movement Disorder Society.He received research support from The Michael J.Fox Foundation,the National Parkinson Foundation,European Union,and Israel Science Foundation,as well as from Teva NNE program,Biogen,and Ionis.He receives support from the Sieratzki Family Foundation and the Aufzien Academic Center in Tel-Aviv University.A.N.received funding from the European Commission,Research Foundation Flanders,King Baudouin Foundation,The Michael J.Fox Foundation,Jacques and Gloria Gossweiler Foundation,and KU Leuven Internal Research Funds.M.H.is an inventor of patents held by the NIH for an immunotoxin for the treatment of focal movement disorders and the H-coil for magnetic stimulationin relation to the latter,he has received license-fee payments from the NIH(from Brainsway).He is on the Medical Advisory Boards of CALA Health and Brainsway(both unpaid positions).He is on the editorial board of approximately 15 journals and receives royalties and/or honoraria from publishing from Cambridge University Press,Ox
文摘There has been a growing appreciation for freezing of gait as a disabling symptom that causes a significant burden in Parkinson’s disease. Previous research has highlighted some of the key components that underlie the phenomenon, but these reductionist approaches have yet to lead to a paradigm shift resulting in the development of novel treatment strategies. Addressing this issue will require greater integration of multi-modal data with complex computational modeling, but there are a number of critical aspects that need to be considered before embarking on such an approach. This paper highlights where the field needs to address current gaps and shortcomings including the standardization of definitions and measurement, phenomenology and pathophysiology, as well as considering what available data exist and how future studies should be constructed to achieve the greatest potential to better understand and treat this devastating symptom.
基金supported by a scholarship from the Ministry of Higher Education and Scientific Research, Libyan Transitional Government (FFM)a scholarship from King Saud University (AB), NIH/NIDCR grants DE11723, DE029012, DE029465+1 种基金Department of Defense grant PR190899, research funds from the Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry (to RTF)the Michigan Musculoskeletal Health Core Center ((NIH/NIAMS P30 AR069620)
文摘Discoidin Domain Receptor 2(DDR2)is a collagen-activated receptor kinase that,together with integrins,is required for cells to respond to the extracellular matrix.Ddr2 loss-of-function mutations in humans and mice cause severe defects in skeletal growth and development.However,the cellular functions of Ddr2 in bone are not understood.Expression and lineage analysis showed selective expression of Ddr2 at early stages of bone formation in the resting zone and proliferating chondrocytes and periosteum.Consistent with these findings,Ddr2^(+)cells could differentiate into hypertrophic chondrocytes,osteoblasts,and osteocytes and showed a high degree of colocalization with the skeletal progenitor marker,Gli1.A conditional deletion approach showed a requirement for Ddr2 in Gli1-positive skeletal progenitors and chondrocytes but not mature osteoblasts.Furthermore,Ddr2 knockout in limb bud chondroprogenitors or purified marrow-derived skeletal progenitors inhibited chondrogenic or osteogenic differentiation,respectively.This work establishes a cell-autonomous function for Ddr2 in skeletal progenitors and cartilage and emphasizes the critical role of this collagen receptor in bone development.
基金The work was supported by the National Natural Science Foundation of China(No.81200981,81,371,407)the Innovation Program of Shanghai Municipal Education Commission(No.13YZ026)the Intramural Program of the National Institute of Neurological Disorders and Stroke.
文摘Photophobia is a common symptom seen in many neurologic disorders,however,its pathophysiology remains unclear.Even the term is ambiguous.In this paper,we review the epidemiology and clinical manifestations of photophobia in neurological disorders,including primary headache,blepharospasm,progressive supranuclear palsy,and traumatic brain injury,discuss the definition,etiology and pathogenesis,and summarize practical methods of diagnosis and treatment.
文摘 Prevention The best treatment is to prevent the illness in the first place or to retard its progression. There is considerable new information about Parkinson's disease genetics and pathophysiology that hopefully will lead to therapy in this regard, but there is still nothing definitive. The only medication for which there are some reasonable data is selegiline, a monoamine oxidase (MAO)-B inhibitor. This drug actually has a symptomatic effect since it prevents the breakdown ofdopamine in the brain. Some trials have shown a beneficial effect separate from its symptomatic effect. The situation is rather controversial, however, and in one study there was an excess of mortality. {4}There are no supportive data for antioxidants such as vitamin E, and a trial of the neurotrophic factor GDNF was not positive.
……
文摘Background: Hazardous alcohol consumption and associated harms are high among young uni- versity students. The university environment is conducive to excessive alcohol consumption with studies finding young university students to drink alcohol at higher levels than their non-university peers. Methods: A random sample of 18 - 24-year-old undergraduate, internal university students completed a survey (n = 2465) to investigate differences in self-reported personal, second-hand and witnessed alcohol-related harms, alcohol expectancies, pre-loading, and friends’ alcohol consumption between low risk and hazardous drinkers. Univariate and multivariate analyses are reported. Results: Almost 40% of students who had consumed alcohol in the past year reported drinking at hazardous levels. Univariate analyses found students who reported hazardous drinking reported significantly higher scores relating to experienced, second-hand, witnessed and academic problems compared to low risk drinkers. Hazardous drinkers were also more likely to pre-load, to drink at higher levels when pre-loading, have more friends who drank alcohol, have more friends who drank at hazardous levels and to score higher on alcohol expectancies. However both low risk and hazardous drinkers experienced a range of harms due to their own drinking including hangover (71.2%), unprotected sex (19.3%), regretted sex (16.8%) and drink-driving (17%). Looking after an intoxicated student (34.3%) and witnessing someone pass out (37.5%) were issues for all drinkers. Experienced alcohol related harms, academic problems, alcohol expectancies, close friends’ level of alcohol consumption, pre-loading in the last four weeks and level of consumption when pre-loading were predictors of hazardous drinking (p < 0.001). Conclusion: Young undergraduate university students are at risk of a range of academic, social, emotional and physical harms associated with their own and other students’ alcohol consumption. There is a need for integrated programs to address university dr
文摘Objective: To explore the role of abnormal neuronal activity in the basal gang lia and thalamus in the generation of dystonia. Methods: Microelectrode recordin g was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucl eus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) d uring surgery. Electromyogram (EMG) was simultaneously recorded in selected musc le groups. Single unit analysis and cross correlations were carried out. Result s: Three hundred and sixty seven neurons were obtained from 29 trajectories (GP i: 13; Vop/Vim:12; STN: 4), 87%exhibited altered neuronal activity including gr ouped discharges in GPi (n=79) and STN (n=37), long lasting neuronal activity ( n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EM G at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0. 64 (n=18) and STN: r2=0.86 (n=17)). Conclusions: Consistent with previous findin gs of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the pre sent data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the prod uction of dystonic movement. Dystonia related neuronal activity observed in mot or thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the developme nt of either generalized or focal dystonia. Significance: These data support a c entral role of the basal ganglia in producing dystonic movements.
文摘Phagocytosis is a fundamental cell biological process exhibited by a wide variety of cell types from single cell organ-isms,which rely on this for feeding,to phagocytes in higher animals,which rely on specialised immune cells for com-bating infecting micro-organisms.In the immune system,both macrophages and neutrophils play roles as phagocytes.Neutrophils are often called'professional phagocytes'because of their remarkable capacity for phagocytosis,beingable to internalise microscopic particles(diam 0.5-3 μm)of virtually any surface material.The efficiency and speedof phagocytosis is,however,increased by coating the surface of the particles with opsonins such as antibodies or thecomplement component C3bi(acting on β2 integrin receptors),and C3bi-accelerated phagocytosis by neutrophils is thefirst line of defence by the innate immune system in vivo,operating in advance of the slower production of antibodies.Understanding the mechanism of phagocytosis is,therefore,clearly an important goal.
基金This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke,National Institutes of Health.
文摘Background:Focal dystonia is a neurological disorder characterized by unwanted muscle spasms.Blepharospasm is a focal dystonia producing an involuntary closure of the eyelid.Its etiology is unknown.Objective:To investigate if there are structural changes in the white and grey matter of blepharospasm patients,and if the changes are related to disease features.Methods:T1 and diffusion-weighted magnetic resonance imaging scans were collected from 14 female blepharospasm patients and 14 healthy matched controls.Grey matter volumes,fractional anisotropy(FA),and mean diffusivity maps were compared between the groups.Based on grey matter differences within the facial portion of the primary motor cortex,the corticobulbar tract was traced and compared between groups.Results:Changes in grey matter in patients included the facial portion of the sensorimotor area and anterior cingulate gyrus.These changes did not correlate with disease duration.Corticobulbar tract volume and peak tract connectivity were decreased in patients compared with controls.There were no significant differences in FA or mean diffusivity between groups.Conclusions:Grey matter changes within the primary sensorimotor and the anterior cingulate cortices in blepharospasm patients may help explain involuntary eyelid closure and the abnormal sensations often reported in this condition.
文摘Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,as well as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are still elusive.Greater understanding of NK cell biology,from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential of NK cells.Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands.The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells.Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,and provide superior graft-versus-tumor (GVT) responses.Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NK cells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologic malignancies.Cellular & Molecular Immunology.2004;1(1):12-21.
