Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs a...Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.展开更多
Purpose:Supracondylar fractures of the humerus cause significant morbidity in children.Nerve damage and loss of fracture reduction are common recognised complications in patients with this injury.Uncertainty surrounds...Purpose:Supracondylar fractures of the humerus cause significant morbidity in children.Nerve damage and loss of fracture reduction are common recognised complications in patients with this injury.Uncertainty surrounds the optimal Kirschner wire configuration and diameter for closed reduction and pinning of these fractures.This study describes current practice and examined the association between wire configuration or diameter and outcomes(clinical and radiological)in the operative management of paediatric supracondylar fractures.Methods:Children presenting w让h GartlandⅡorⅢsupracondylar fractures at five hospitals in southwest England were eligible for inclusion.Collaborators scrutinised paper and electronic case notes.Outcome measures were maintenance of reduction and iatrogenic nerve injury.Results:Altogether 209 patients were eligible for inclusion:15.7%had a documented neurological deficit at presentation;3.9%who were neurologically intact at presentation sustained a new deficit caused by treatment and 13.4%experienced a clinically significant loss of reduction following fixation.Maintenance of reduction was significantly better in patients treated specifically with crossed×3 Kirschner wire configuration compared to all other configurations.The incidence of iatrogenic nerve injury was not significantly different between groups treated with different wire configurations.Conclusion:We present a large multicentre cohort study showing that crossed×3 Kirschner wires are associated with better maintenance of reduction than crossed×2 or lateral entry wires.Greater numbers would be required to properly investigate nerve injury relating to operative management of supracondylar fractures.We found significant variations in practice and compliance w让h the British Orthopaedic Association Standard for Trauma(BOAST)11 guidelines.展开更多
Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1...Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1 a(IRE1 a),double-stranded RNA-dependent protein kinase(PKR)-like ER kinase(PERK)and activating transcription factor 6(ATF6)signaling pathways,is a protective cellular response activated by ER stress.However,UPR activation can also induce cell death upon persistent ER stress.The liver is susceptible to ER stress given its synthetic and other biological functions.Numerous studies from human liver samples and animal disease models have indicated a crucial role of ER stress and the UPR signaling pathways in the pathogenesis of liver diseases,including non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease(ALD),alpha-1 antitrypsin(AAT)deficiency(AATD),cholestatic liver disease,drug-induced liver injury,ischemia/reperfusion(I/R)injury,viral hepatitis and hepatocel-lular carcinoma(HCC).Extensive investigations have demonstrated the potential underlying mechanisms of the induction of ER stress and the contribution of the UPR pathways during the development of the diseases.Moreover,ER stress and the UPR proteins and genes have become emerging therapeutic targets to treat liver diseases.展开更多
Hepatic artery pseudoaneurysms(HAP)are rare events,particularly after liver biopsy,but can be associated with serious complications.Therefore a high suspicion is necessary for timely diagnosis and appropriate treatmen...Hepatic artery pseudoaneurysms(HAP)are rare events,particularly after liver biopsy,but can be associated with serious complications.Therefore a high suspicion is necessary for timely diagnosis and appropriate treatment.We report on a case of HAP that potentially formed after a liver biopsy in a patient with sarcoidosis.The HAP in our case was virtually undetectable initially by angiography but resulted in several complications including recurrent gastrointestinal bleeding,hemorrhagic cholecystitis and finally hepatic infarction with abscess formation until it became detectable at a size of 5-mm.The patient remains asymptomatic over a year after endovascular embolization of the HAP.In this report,we demonstrate that a small HAP can avoid detection by angiography at an early stage while being symptomatic for a prolonged course.A high clinical suspicion with a close clinical/radiological follow-up is needed in symptomatic patients with history of liver biopsy despite initial negative work up.Once diagnosed,HAP can be safely and effectively treated by endovascular embolization.展开更多
This is the third paper in a series connected with our Multiwavelength Quasar Survey. The survey is aimed to provide a quasar sample more complete than any previous survey by using a combined selection technique to re...This is the third paper in a series connected with our Multiwavelength Quasar Survey. The survey is aimed to provide a quasar sample more complete than any previous survey by using a combined selection technique to reduce selection effects. We present the observational results for the X-ray candidates in field f836. We found 15 X-ray AGNs in this field of which eight are new discoveries. The X-ray data and optical spectra of these AGNs are given. We give the X-ray candidate selection criteria, which proved to be highly efficient in isolating X-ray AGNs.展开更多
X-ray loud M dwarfs are a major source of by-products （contamination） in the X-ray band of the multiwavelength quasar survey. As a by-product, the low dispersion spectra of 22 M dwarfs are obtained in which the spec...X-ray loud M dwarfs are a major source of by-products （contamination） in the X-ray band of the multiwavelength quasar survey. As a by-product, the low dispersion spectra of 22 M dwarfs are obtained in which the spectra of 16 sources are taken for the first time. The spectral types and distances of the sample are given based on spectral indices CaH2, CaH3, and TiO5. The parameter ζ TiO/CaH is calculated to separate the different metallicity classes among dwarfs, subdwarfs and extreme subdwarfs. We also discuss the distributions in the diagrams of log（L x /L bol ）, the ratio between X-ray and bolometric luminosity versus spectral type and infrared colors.展开更多
We aim to provide a quasar sample that is more complete than any previous surveys by using a combined selection technique to reduce the selection effects. Here we present the observational results for the X-ray candid...We aim to provide a quasar sample that is more complete than any previous surveys by using a combined selection technique to reduce the selection effects. Here we present the observational results for the X-ray candidates in the field of the Leo Cluster. We found 33 X-ray AGNs in this field of which 10 are new discoveries. The X-ray data and optical spectra of these AGNs are given. We also study the near-IR properties of the X-ray-selected AGNs by using the data from 2MASS. Most of the AGNs in our sample span the color range 0.0〈B-J〈2.5,1.0〈 J-Ks 〈2.0 and 0.5〈H-Ks〈1.2.展开更多
This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morpholog...This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morphological phenotype.Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain,SAK950 showed that many induced a“rounded”phenotype.We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes.We show that five of the strains produced streptothricin and that 26 strains produced polyenes,including fungichromin,filipin and candicidin,the last of which was produced by 24 strains.A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S.albidoflavus whilst those that additionally produced streptothricin were related to S.enissocaesilis.A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern.The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S.pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.展开更多
The competition between coral and algae in marine reefs is pervasive through geologic time;that competition determines the structure and composition of reef communities, which we see in the fossil record. However, the...The competition between coral and algae in marine reefs is pervasive through geologic time;that competition determines the structure and composition of reef communities, which we see in the fossil record. However, the relationships between coral and calcareous algae in reefs are poorly understood. To study this relationship, several hand samples and thin sections were examined from nine different foralgal reef localities around the world. Foralgal reefs typically extend from about 20 m depth or shallower on the seaward side of the reef. The first section is Salt Mountain, Alabama, which preserves a Paleocene reef. It contains a high percentage of red coralline algae with benthic foraminifera. The second section is IDOP-U1376, IIA Limestone, it is Middle Eocene, in the form of an isolated reef sandwiched between two igneous beds. The third section is the Utoe’ Limestone, New Caledonia, it is Middle Eocene in age and is composed mainly of grain-boundstone units with some igneous interlayered. The fourth section is the Darnah Formation in the West-Darnah roadcut section, Northeast Libya, it is Middle Eocene in age, it is composed of highly fossiliferous limestone (corals, red coralline algae, echinoids, mollusks, foraminifers, and bryozoans). The fifth section, the Al Bayda Formation (Algal Limestone Member) in Northeast Libya, is in the Drayanah—Al Abyar roadcut, Northeast Libya, it has several species of algae but also includes a high percentage of buildups of coral species. The sixth section is the Oligo-Miocene Al Faidiyah Formation (Al Fatayah Cement Quarry) limestone unit in Northeast Libya. The seventh section is (Core-core 20) late-early to middle Miocene Limestone Unit-Cicuco Field, NW Colombia. The eighth section is the Benghazi Formation at Benghazi Cement Quarry, in Northeast Libya, it is fossiliferous limestone, consisting of coral, algae, mollusks, and echinoids. The ninth and tenth sections are Quaternary reefs in the Bahamas and the Florida Keys, respectively. These reefs contain a high percentag展开更多
Ophiolitic podiform chromitites for a long time have been considered as ＂cumulates＂ formed by harzburgite- melt interaction and related melt mixing at the upper part of the suboceanic mantle to the Moho transition z...Ophiolitic podiform chromitites for a long time have been considered as ＂cumulates＂ formed by harzburgite- melt interaction and related melt mixing at the upper part of the suboceanic mantle to the Moho transition zone. Within many existing concepts, which are in a focus of this workshop, there is one suggesting that some portion of chromitites originate from deep mantle,展开更多
基金The reported work was in part supported by research grants from the National Institutes of Health(AR50142 and AR054381 to RCH and HHL)RW,JG,and OI were recipients of the Pritzker Summer Research Fellowship funded through a NIH T-35 training grant(NIDDK).AH was a recipient of the Urban Leadership Fellowship from Miami University.
文摘Bone Morphogenetic Proteins(BMPs)are a group of signaling molecules that belongs to the Transforming Growth Factor-b(TGF-b)superfamily of proteins.Initially discovered for their ability to induce bone formation,BMPs are now known to play crucial roles in all organ systems.BMPs are important in embryogenesis and development,and also in maintenance of adult tissue homeostasis.Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects,highlighting the essential functions of BMPs.In this review,we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development.A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.
文摘Purpose:Supracondylar fractures of the humerus cause significant morbidity in children.Nerve damage and loss of fracture reduction are common recognised complications in patients with this injury.Uncertainty surrounds the optimal Kirschner wire configuration and diameter for closed reduction and pinning of these fractures.This study describes current practice and examined the association between wire configuration or diameter and outcomes(clinical and radiological)in the operative management of paediatric supracondylar fractures.Methods:Children presenting w让h GartlandⅡorⅢsupracondylar fractures at five hospitals in southwest England were eligible for inclusion.Collaborators scrutinised paper and electronic case notes.Outcome measures were maintenance of reduction and iatrogenic nerve injury.Results:Altogether 209 patients were eligible for inclusion:15.7%had a documented neurological deficit at presentation;3.9%who were neurologically intact at presentation sustained a new deficit caused by treatment and 13.4%experienced a clinically significant loss of reduction following fixation.Maintenance of reduction was significantly better in patients treated specifically with crossed×3 Kirschner wire configuration compared to all other configurations.The incidence of iatrogenic nerve injury was not significantly different between groups treated with different wire configurations.Conclusion:We present a large multicentre cohort study showing that crossed×3 Kirschner wires are associated with better maintenance of reduction than crossed×2 or lateral entry wires.Greater numbers would be required to properly investigate nerve injury relating to operative management of supracondylar fractures.We found significant variations in practice and compliance w让h the British Orthopaedic Association Standard for Trauma(BOAST)11 guidelines.
基金This work was supported by USA National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)R01 DK093807.
文摘Endoplasmic reticulum(ER)stress occurs when ER homeostasis is perturbed with accumulation of unfolded/misfolded protein or calcium depletion.The unfolded protein response(UPR),comprising of inositol-requiring enzyme 1 a(IRE1 a),double-stranded RNA-dependent protein kinase(PKR)-like ER kinase(PERK)and activating transcription factor 6(ATF6)signaling pathways,is a protective cellular response activated by ER stress.However,UPR activation can also induce cell death upon persistent ER stress.The liver is susceptible to ER stress given its synthetic and other biological functions.Numerous studies from human liver samples and animal disease models have indicated a crucial role of ER stress and the UPR signaling pathways in the pathogenesis of liver diseases,including non-alcoholic fatty liver disease(NAFLD),alcoholic liver disease(ALD),alpha-1 antitrypsin(AAT)deficiency(AATD),cholestatic liver disease,drug-induced liver injury,ischemia/reperfusion(I/R)injury,viral hepatitis and hepatocel-lular carcinoma(HCC).Extensive investigations have demonstrated the potential underlying mechanisms of the induction of ER stress and the contribution of the UPR pathways during the development of the diseases.Moreover,ER stress and the UPR proteins and genes have become emerging therapeutic targets to treat liver diseases.
文摘Hepatic artery pseudoaneurysms(HAP)are rare events,particularly after liver biopsy,but can be associated with serious complications.Therefore a high suspicion is necessary for timely diagnosis and appropriate treatment.We report on a case of HAP that potentially formed after a liver biopsy in a patient with sarcoidosis.The HAP in our case was virtually undetectable initially by angiography but resulted in several complications including recurrent gastrointestinal bleeding,hemorrhagic cholecystitis and finally hepatic infarction with abscess formation until it became detectable at a size of 5-mm.The patient remains asymptomatic over a year after endovascular embolization of the HAP.In this report,we demonstrate that a small HAP can avoid detection by angiography at an early stage while being symptomatic for a prolonged course.A high clinical suspicion with a close clinical/radiological follow-up is needed in symptomatic patients with history of liver biopsy despite initial negative work up.Once diagnosed,HAP can be safely and effectively treated by endovascular embolization.
基金the National Natural Science Foundation of China.
文摘This is the third paper in a series connected with our Multiwavelength Quasar Survey. The survey is aimed to provide a quasar sample more complete than any previous survey by using a combined selection technique to reduce selection effects. We present the observational results for the X-ray candidates in field f836. We found 15 X-ray AGNs in this field of which eight are new discoveries. The X-ray data and optical spectra of these AGNs are given. We give the X-ray candidate selection criteria, which proved to be highly efficient in isolating X-ray AGNs.
基金supported by the Scientific Research Foundation of Beijing Normal Universitythe National Natural Science Foundation of China (Grant No.10778717)supported by the Open Project Program of the Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences
文摘X-ray loud M dwarfs are a major source of by-products （contamination） in the X-ray band of the multiwavelength quasar survey. As a by-product, the low dispersion spectra of 22 M dwarfs are obtained in which the spectra of 16 sources are taken for the first time. The spectral types and distances of the sample are given based on spectral indices CaH2, CaH3, and TiO5. The parameter ζ TiO/CaH is calculated to separate the different metallicity classes among dwarfs, subdwarfs and extreme subdwarfs. We also discuss the distributions in the diagrams of log（L x /L bol ）, the ratio between X-ray and bolometric luminosity versus spectral type and infrared colors.
基金the National Natural Science Foundation of China.
文摘We aim to provide a quasar sample that is more complete than any previous surveys by using a combined selection technique to reduce the selection effects. Here we present the observational results for the X-ray candidates in the field of the Leo Cluster. We found 33 X-ray AGNs in this field of which 10 are new discoveries. The X-ray data and optical spectra of these AGNs are given. We also study the near-IR properties of the X-ray-selected AGNs by using the data from 2MASS. Most of the AGNs in our sample span the color range 0.0〈B-J〈2.5,1.0〈 J-Ks 〈2.0 and 0.5〈H-Ks〈1.2.
基金the Francis Crick Institute which receives its core funding from Cancer Research UK(FC001121)the UK Medical Research Council(FC001121)+2 种基金the Wellcome Trust(FC001121)In addition,this work was supported by a Wellcome Trust grant to P.N.(Grant Number 093917)Demuris Ltd.
文摘This study was designed to identify and investigate bioactive natural product compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe and induce a“rounded”or“small”cellular morphological phenotype.Bioassays using a range of antifungal agents against a multidrug-sensitive fission yeast strain,SAK950 showed that many induced a“rounded”phenotype.We then investigated whether 46 of the actinomycete strains identified in our previous study as inducing a similar phenotype produced antifungal agents of similar classes.We show that five of the strains produced streptothricin and that 26 strains produced polyenes,including fungichromin,filipin and candicidin,the last of which was produced by 24 strains.A taxonomic study of the strains indicated that the majority of the candicidin only producers were Streptomyces hydrogenans and S.albidoflavus whilst those that additionally produced streptothricin were related to S.enissocaesilis.A follow-up study to investigate the natural products made by related strains indicated that they followed a similar pattern.The identification of several compounds from the actinomycete strains similar to the antifungal agents initially tested confirm the validity of an approach using the S.pombe morphological phenotype and actinomycete taxonomy as a predictive tool for natural product identification.
文摘The competition between coral and algae in marine reefs is pervasive through geologic time;that competition determines the structure and composition of reef communities, which we see in the fossil record. However, the relationships between coral and calcareous algae in reefs are poorly understood. To study this relationship, several hand samples and thin sections were examined from nine different foralgal reef localities around the world. Foralgal reefs typically extend from about 20 m depth or shallower on the seaward side of the reef. The first section is Salt Mountain, Alabama, which preserves a Paleocene reef. It contains a high percentage of red coralline algae with benthic foraminifera. The second section is IDOP-U1376, IIA Limestone, it is Middle Eocene, in the form of an isolated reef sandwiched between two igneous beds. The third section is the Utoe’ Limestone, New Caledonia, it is Middle Eocene in age and is composed mainly of grain-boundstone units with some igneous interlayered. The fourth section is the Darnah Formation in the West-Darnah roadcut section, Northeast Libya, it is Middle Eocene in age, it is composed of highly fossiliferous limestone (corals, red coralline algae, echinoids, mollusks, foraminifers, and bryozoans). The fifth section, the Al Bayda Formation (Algal Limestone Member) in Northeast Libya, is in the Drayanah—Al Abyar roadcut, Northeast Libya, it has several species of algae but also includes a high percentage of buildups of coral species. The sixth section is the Oligo-Miocene Al Faidiyah Formation (Al Fatayah Cement Quarry) limestone unit in Northeast Libya. The seventh section is (Core-core 20) late-early to middle Miocene Limestone Unit-Cicuco Field, NW Colombia. The eighth section is the Benghazi Formation at Benghazi Cement Quarry, in Northeast Libya, it is fossiliferous limestone, consisting of coral, algae, mollusks, and echinoids. The ninth and tenth sections are Quaternary reefs in the Bahamas and the Florida Keys, respectively. These reefs contain a high percentag
文摘Ophiolitic podiform chromitites for a long time have been considered as ＂cumulates＂ formed by harzburgite- melt interaction and related melt mixing at the upper part of the suboceanic mantle to the Moho transition zone. Within many existing concepts, which are in a focus of this workshop, there is one suggesting that some portion of chromitites originate from deep mantle,
