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Osteoblast-restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes

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Bone Research 2013年第1期1卷 85-97页

作者： Vandana Singhal Brian c.Goh Mary L.Bouxsein Marie-claude Faugere douglas J.DiGirolamo Department of Orthopaedic Surgery Johns Hopkins University School of MedicineBaltimoreMDUSA center for Advanced Orthopedic Studies Beth Israel Deaconess Medical Center and Harvard Medical SchoolBostonMAUSA Albert B.chandler Medical center University of KentuckyLexingtonKYUSA

Growth hormone （GH） exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 （IGF-1） in liver and skeletal tissues. To examine the requirement for the GH receptor （GHR） in osteoblast function in bone, we used cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions. Osteoblasts lacking GHR exhibited reduced IGF-l-induced Erk and Akt phosphorylation and attenuated IGF-1-induced proliferation and anti-apoptotic action. In addition, differentiation was modestly impaired in osteoblasts lacking GHR, as demonstrated by reduced alkaline phosphatase staining and calcium deposition. In order to determine the requirement for the GHR in bone in vivo, we generated mice lacking the GHR specifically in osteoblasts （△GHR）, which were born at the expected Mendelian frequency, had a normal life span and were of normal size. Three week-old, female AGHR mice had significantly reduced osteoblast numbers, consistent with the in vitro data. By six weeks of age however, female AGHR mice demonstrated a marked increase in osteoblasts, although mineralization was impaired; a phenotype similar to that observed previously in mice lacking IGF-1R specifically in osteoblasts. The most striking phenotype occurred in male mice however, where disruption of the GHR from osteoblasts resulted in a ＂feminization＂ of bone geometry in 16 week-old mice, as observed by facT. These results demonstrate that the GHR is required for normal postnatal bone development in both sexes. GH appears to serve a primary function in modulating local IGF-1 action. However, the changes in bone geometry observed in male AGHR mice suggest that, in addition to facilitating IGF-1 action, GH may function to a greater

关键词： growth hormone osteoblasts knockout mice bone sexual dimorphism

Application of artificial intelligence in pediatrics: past, present and future

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World Journal of Pediatrics 2019年第2期15卷 105-108页

作者： Li-Qi Shu Yi-Kan Sun Lin-Hua Tan Qiang Shu anthony c.chang School of Medicine and Health Sciences George Washington UniversityWashingtonD.C.20037USA Faculty of Medicine University of New South WalesSydneyNSW 2052Australia children's Hospital Zhejiang University School of MedicineHangzhou 310052China The Sharon Disney Lund Medical Intelligence and Innovation Institute(MI3) Children's Hospital of Orange CountyOrangeCA 92868USA

Artificial intelligence (AI) is a very active computer science research field aiming to develop systems that mimic human intelligence and is helpful in many human activities,including ***,it is no surprise that innova... 详细信息

关键词： Application past present

SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity

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Bone Research 2018年第2期6卷 132-144页

作者： chunlin Zuo Lijun Wang Raghavendra M.Kamalesh Margot E.Bowen douglas c.Moore Mark S.Dooner anthony M.Reginato Qian Wu christoph Schorl Yueming Song Matthew L.Warman Benjamin G.Neel Michael G.Ehrlich Wentian Yang Department of Orthopaedics Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Orthopaedic Research Laboratories and Howard Hughes Medical Institute Boston Children's Hospital and Department of GeneticsHarvard Medical SchoolBostonMA 02115USA Division of Hematology and Oncology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Division of Rheumatology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Department of Pathology and Laboratory Medicine University of Connecticut Health CenterFarmingtonCT 06030USA Department of Molecular and cell Biology and Biochemistry Brown University70 Ship StreetProvidenceRI 02912USA Department of Orthopedic Surgery West China Hospital of Sichuan UniversityChengdu 610041 Laura and Issac Perlmutter cancer center NYU Langone Medical CenterNew YourkNY 10016USA Department of Endocrinology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OcP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OcPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂cre-lox P＂-mediated gene ***2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OcPs become chondrocytes and not osteoblasts. consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, col2a1, and col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PcR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OcP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.

关键词： SHP2 regulates skeletal cell modifying SOX9 expression transcriptional activity SOX

Impact of community strategy package on uptake of reproductive tract infections health services among young street females in the municipality of Eldoret,Kenya

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Gynecology and Obstetrics clinical Medicine 2023年第1期3卷 60-64页

作者： c Violet Maritim anthony Wanyoro John Maingi Jackim Nyamari Murima Ng'ang'a Department of Population and Reproductive Health Faculty of Public HealthKenyatta UniversityNairobiP.O Box 184-40110SonghorKenya Department of Obstetrics and Gynecology Faculty of Health SciencesKenyatta UniversityNairobiKenya Department of Microbiology and Biochemistry Faculty of Applied SciencesKenyatta UniversityNairobiKenya Department of Environmental and Occupational Health Faculty of Public HealthKenyatta UniversityNairobiKenya Department of Infectious Diseases Ministry of HealthKenya

Background:Despite the intervention of free medical care services for street children by a dedicated clinic in Eldoret municipality,health care service of young street females(YSFs)is still *** present study aimed to evaluate the impact of the community strategy package on the uptake of reproductive tract infections(RTI)health services among the target *** and methods:A pre-test-post-test quasi-experimental with a qualitative and quantitative approach was applied among the YSFs aged 10-24 *** study used structured questionnaires and key informant interviews to collect data from the ***:The study enrolled a total of 77 young street females in Eldoret municipality.A significantly higher proportion of respondents reportedly first sought treatment for RTI at a health facility after the implementation of the community strategy package(97.1%)when compared to the proportion of respondents who first sought treatment at a health facility in the pre-intervention phase(51.0%)(pcantly after the introduction of the intervention;72.0%and 94.1%of the respondents sought treatment early during the pre-intervention and post-intervention phase,respectively(pconclusion:The study recommends the adoption of the community strategy as an intervention to increase the uptake of RTIs health services and promotion of the reproductive health of young street females.

关键词： Reproductive tract infections Young street females(YSFs) Reproductive health services community strategy package

An apatite U-Pb thermal history map for the northern Gawler craton,South Australia

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Geoscience Frontiers 2018年第5期9卷 1293-1308页

作者： James W.Hall Stijn Glorie anthony J.Reid Samuel c.Boone Alan S.collins ANDrew Gleadow Tectonics Resources and Exploration (TRaX) Department of Earth Sciences University of Adelaide Geological Survey of South Australia Department of State Development School of Earth Sciences The University of Melbourne

Apatite U-Pb thermochronology was applied to granitoid basement samples across the northern Gawler craton to unravel the Proterozoic, post-orogenic, cooling history and to examine the role of major fault zones during cooling. Our observations indicate that cooling following the ~2500 Ma Sleaford Orogeny and ~1700 Ma Kimban Orogeny is restricted to the christie and Wilgena Domains of the central northern Gawler craton. The northern Gawler craton mainly records post-Hiltaba Event(~1590 Ma) U-Pb cooling ages. cooling following the ~1560 Ma Kararan Orogeny is preserved within the coober Pedy Ridge,Nawa Domain and along major shear zones within the south-western Fowler Domain. The Nawa Domain samples preserve U-Pb cooling ages that are >150 Ma younger than the samples within the coober Pedy Ridge and Fowler Domain, indicating that later(~1300 Ma) fault movement within the Nawa Domain facilitated cooling of these samples, caused by arc collision in the Madura Province of eastern Western Australia. When compared to^(40)Ar/^(39) Ar from muscovite, biotite and hornblende, our new apatite U-Pb ages correlate well, particularly in regions of higher data density. Our data also preserve a progressive younging of U-Pb ages from the nucleus of the craton to the periphery with a stark contrast in U-Pb ages across major structures such as the Karari Shear Zone and the Southern Overthrust, which indicates the timing of reactivation of these major crustal structures. Although this interpolation was based solely on thermochronological data and did not take into account structural or other geological data, these maps are consistent with the structural architecture of the Gawler craton and reveal the thermal footprint of known tectonic and magmatic events in the Gawler craton.

关键词： Apatite U-Pb Gawler craton Karari Shear Zone Thermochronology Hiltaba event

AtPEPTIDE REcEPTOR_2 mediates the AtPEPTIDE1‐induced cytosolic ca^(2+) trise, which is required for the suppression of Glutamine Dumper gene expression in Arabidopsis roots

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Journal of Integrative Plant Biology 2014年第7期56卷 684-694页

作者： chunli Ma Jie Guo Yan Kang Kohei Doman anthony c.Bryan Frans E.Tax Yube Yamaguchi Zhi Qi college of Life Sciences Inner Mongolia University crop Physiology Laboratory Graduate School of Agriculture Hokkaido University Department of Molecular and cellular Biology and School of Plant Sciences University of Arizona Graduate School of Life and Environmental Sciences Osaka Prefecture University

AtPEPTIDE REcEPTOR2 （AtPEPR2） is a member of leucine-rich repeat receptor-like kinase family and binds to a group of AtPROPEP gene-encoded endogenous peptides, AtPeps. Previously, we found that AtPEPR2 plays a moderate role in the AtPep1-mediated innate immunity responses in Arabidopsis leaf. In this study, we found that AtPEPR2 promoter has strong activity in the vascular tissues of the roots and the atpepr2 mutants showed a moderate but significantly shorter root phenotype. AtPEPR2 partial y mediated AtPep1-induced root elongation inhibition. AtPep1-triggered cytosolic ca2t transient rise in roots showed partial dependence on AtPEPR2 and ful y on extracellular ca2t （[ca2t]ext）. Transcriptional profiling analysis found that expression of 75% of AtPep1-modulated genes in roots was ful y dependent on AtPEPR2, of which two dramatical y induced genes showed partial dependence on the [ca2t]ext. Arabidopsis genome contains seven Glutamine Dumpers genes （AtGDUs）, encoding amino acid exporters. Three of them （AtGDU2, 3, 5） were among the top 10 genes that were＆amp;nbsp;downregulated by AtPep1 through AtPEPR2 ful y dependent pathway. Treatment with AtPep1 strongly suppressed pro-moter activity of AtGDU3 in roots, which was relieved by chelating [ca2t]ext. Arabidopsis overexpressing AtGDU3 showed a shorter root phenotype and decreased sensitivity to the AtPep1-mediated inhibition of root elongation. Taken together, this study demonstrated a significant role of AtPEPR2 in the AtPep1-mediated signaling in the roots.

关键词： Arabidopsis AtPeptide cytosolic ca2+ receptor-like kinase root

Effect of lignite amendment on carbon and nitrogen mineralization from raw and composted manure during incubation with soil

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Pedosphere 2022年第5期32卷 785-795页

作者： Robert IMPRAIM anthony WEATHERLEY Deli cHEN Helen SUTER School of Agriculture and Food Faculty of Veterinary and Agricultural Sciences.The University of MelbourneParkvilleVictoria 3010(Australia)

The application of animal manure as a source of plant nutrients requires the determination of the amount and pattern of nutrient mineralization from manure.A laboratory incubation study was conducted to investigate the influence of lignite amendment and lignite type on carbon(c)and nitrogen(N)mineralization in raw(feedstock)and composted cattle manure following application to soil at 30 and 60 t ha^(-1).The mineralization of c and N was determined by measuring changes in cO_(2) evolution and mineral N(NH_(4)^(+)-N+NO_(3)^(-)-N)over 40 *** results showed that lignite amendment suppressed the amount of manure c mineralized in both feedstock and compost,with the effect being more pronounced in the *** the 40-d incubation,the percentage of applied c mineralized was 26.4%-27.8%and 16.3%-21.4%in unamended and lignite-amended feedstocks,*** corresponding c mineralized in the composts was 12.4%-14.1%and 3.5%-6.5%.Lignite had no significant effect on the net N mineralized in compost(4.8%-6.7%and2.5%-7.8%in unamended and lignite-amended composts,respectively).Lignite had either no effect or increased the net N mineralized in feedstock(from3.2%-8.7%without lignite to 10.4%-13.5%)depending on the type of lignite *** study suggests that using lignite-amended manure,especially when composted,has the potential to build up soil organic c without limiting the availability of mineral N.

关键词： cO_(2)evolution manure mineralization mineral N nitrification soil incubation

Stress reduction via neuro-emotional technique to achieve the simultaneous resolution of chronic low back pain with multiple inflammatory and biobehavioural indicators:A randomized,double-blinded,placebo-controlled trial

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Journal of Integrative Medicine 2022年第2期20卷 135-144页

作者： Peter Bablis Henry Pollard anthony L.Rosner Universal Health New South Wales 2028Australia School of Medical and Applied Sciences University of Central QueenslandBrisbaneNew South Wales 4000Australia Medical Information Services MA 02479-4149United States

Background:Beginning with the concepts of stress developed by Selye,an approach to stress and pain management,known as neuro-emotional technique(NET),has been *** is a treatment approach based on the principle that the stressor effects of dormant and/or current unresolved issues or trauma are what determine one’s bodily *** responses are relatively personalized to the conditioned,experiential and emotional reality of the ***:To determine the effect of NET on patients with chronic low back pain(cLBP)over ***,setting,participants,and interventions:In a randomized,double-blinded,placebo-controlled study conducted in a single clinic,NET or control treatments were given twice weekly for 4 weeks in a population of 112 *** outcome measures:Outcome measures,including Oswestry Disability Index,Quadruple Visual Analogue Scale,the psychoneuroimmunology markers of blood serum levels of c-reactive protein,tumour necrosis factor-a,interleukin-1(IL-1),IL-6,and IL-10,and 10 dimensions of the Short Form Health Survey scale,were assessed at baseline and at 1,3 and 6 months following the intervention ***:compared to placebo,NET produced clinical and statistical significance(Pclines of virtually all physiological,pain and disability markers,accompanied by gains in quality-of-life indicators at 0(baseline),1,3 and 6 *** of the percentages of patients whose 5 biomarkers lay outside the normative range were achieved at 1,3 and 6 months by NET but not control ***:A randomized,controlled trial of cLBP patients indicated that 8 NET interventions,compared to placebo,produced clinically and statistically significant reductions in pain,disability and inflammatory biomarkers,and improvements in quality-of-life measures.

关键词： Neuro-emotional technique Biopsychosocial model Emotion Mind-body therapies Inflammation Biomarker

Ionic liquid/tetraglyme hybrid Mg[TFSI]_2 electrolytes for rechargeable Mg batteries

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Green Energy & Environment 2019年第2期4卷 146-153页

作者： Zheng Ma Maria Forsyth douglas R.MacFarlane Mega Kar School of chemistry Faculty of Science Monash University ARc centre of Excellence for Electromaterials Science IFM – Institute for Frontier Materials Deakin University

The electrochemical reversibility of Mg in hybrid electrolytes based on mixtures of ionic liquid and glyme based organic solvents was investigated for applications in rechargeable magnesium batteries(RMBs). The electrolytes demonstrate reversible reduction and oxidation of Mg only after being pre-treated with the dehydrating agent, magnesium borohydride, Mg[BH_4]_2, highlighting the importance of removing water in Mg based electrolytes. The addition magnesium di[bis(trifluoromethanesulfonyl)imide](Mg[TFSI]_2)(0.3 M) to N-butyl-n-methyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide [c4 mpyr][TFSI]/tetraglyme at a mole ratio of 1:2 showed stable cV cycling over almost 300 cycles while scanning electron microscopy(SEM) and X-ray diffraction(XRD) confirmed Mg deposition, showing non-dendritic morphology and a well-aligned growth. Further thermogravimetric analysis(TGA) demonstrated a mass retention of 79% at 250℃ for this electrolyte suggesting that the presence of the ionic liquid increases thermal stability substantially making these hybrid electrolytes compatible for RMBs.

关键词： Mg[TFSI]2 Ionic liquids Tetraglyme Rechargeable Mg battery Mg[BH4]2 dehydrate reagent