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journal of Clinical and Translational Hepatology 2018年第3期6卷 264-275页

作者： james j.Connolly Kohtaro Ooka joseph K.Lim Department of Internal Medicine Yale University School of MedicineNew HavenCTUSA Division of Gastroenterology Hepatology and NutritionUniversity of Pittsburgh Medical CenterPittsburghPAUSA Yale Liver Center Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA

Non-alcoholic steatohepatitis(NASH)results from inflammation and hepatocyte injury in the setting of hepatic ***-alcoholic steatohepatitis increases the risk of progression to liver fibrosis and cirrhosis,and is the most rapidly growing etiology for liver failure and indication for liver transplantation in the *** loss and lifestyle modification remain the standard first-line treatment,as no USA Food and Drug Administration-approved pharmacotherapy currently *** past decade has seen an explosion of interest in drug development targeting pathologic pathways in non-alcoholic steatohepatitis,with numerous phase 2 and 3 trials currently in ***,we concisely review the major targets and mechanisms of action by class,summarize results from com-pleted pivotal phase 2 studies,and provide a detailed outline of key active studies with trial data for drugs in development,including obeticholic acid,elafibranor,cenicriviroc and selonsertib.

关键词： Fatty liver Non-alcoholic steatohepatitis Clinical trials Pharmacotherapy Obeticholic acid

Strigolactones and the Regulation of Pea Symbioses in Response to Nitrate and Phosphate Deficiency

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Molecular Plant 2013年第1期6卷 76-87页

作者： Eloise Foot Kaori Yoneyama Cassandra j. Hugill Laura j. Quittenden james B. Reidt School of Plant Science University of Tasmania Private Bag 55 Hobart Tasmania 7001 Australia Weed Science Centre Utsunomiya University 350 Mine-machi Utsunomiya 321-8505 Japan

New roles for the recently identified group of plant hormones, the strigolactones, are currently under active investigation. One of their key roles is to regulate plant symbioses. These compounds act as a rhizosphere signal in arbuscular mycorrhizal symbioses and as a positive regulator of nodulation in legumes. The phosphorous and nitrogen status of the soil has emerged as a powerful regulator of strigolactone production. However, until now, the potential role of strigolactones in regulating mycorrhizal development and nodulation in response to nutrient deficiency has not been proven. In this paper, the role of strigolactone synthesis and response in regulating these symbioses is examined in pea （Pisum sativum L.）. Pea is well suited to this study, since there is a range of well-characterized strigolactone bio- synthesis and response mutants that is unique amongst legumes. Evidence is provided for a novel endogenous role for strigolactone response within the root during mycorrhizal development, in addition to the action of strigolactones on the fungal partner. The strigolactone response pathway that regulates mycorrhizal development also appears to dif- fer somewhat from the response pathway that regulates nodulation. Finally, studies with strigolactone-deficient pea mutants indicate that, despite strong regulation of strigolactone production by both nitrogen and phosphate, strigolac- tones are not required to regulate these symbioses in response to nutrient deficiency.

关键词： Strigolactones nodulation mycorrhizae nitrate phosphate pea.

Diffusion of lithium ions in Lithium-argyrodite solid-state electrolytes

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npj Computational Materials 2020年第1期6卷 326-335页

作者： Ardeshir Baktash james C.Reid Tanglaw Roman Debra j.Searles Centre for Theoretical and Computational Molecular Science Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandSt Lucia 4072 QLDAustralia School of Mathematics and Physics The University of QueenslandSt Lucia 4072 QLDAustralia School of Physics The University of SydneyCamperdown 2006 NSWAustralia School of Chemistry and Molecular Biosciences The University of QueenslandSt Lucia 4072 QLDAustralia

The use of solid-state electrolytes to provide safer,next-generation rechargeable batteries is becoming more feasible as materials with greater stability and higher ionic diffusion coefficients are ***,accurate determination of diffusion coefficients in solids is problematic and reliable calculations are highly sought-after to understand how their structure can be modified to improve their *** this paper we compare diffusion coefficients calculated using nonequilibrium and equilibrium ab initio molecular dynamics simulations for highly diffusive solid-state electrolytes,to demonstrate the accuracy that can be ***,we show that ab initio nonequilibrium molecular dynamics can be used to determine diffusion coefficients when the diffusion is too slow for it to be feasible to obtain them using ab initio equilibrium simulations.

关键词： diffusion nonequilibrium feasible

Keeping an eye on the diabetic foot: The connection between diabetic eye disease and wound healing in the lower extremity

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World journal of Diabetes 2022年第12期13卷 1035-1048页

作者： David j Ramsey james T Kwan Arjun Sharma Department of Ophthalmology Lahey Hospital and Medical CenterBurlingtonMA 01805United States Department of Ophthalmology Tufts University School of MedicineBostonMA 02111United States

Diabetic eye disease is strongly associated with the development of diabetic foot ulcers(DFUs).DFUs are a common and significant complication of diabetes mellitus(DM)that arise from a combination of micro-and macrovascular *** and associated metabolic dysfunction in DM lead to impaired wound healing,immune dysregulation,peripheral vascular disease,and diabetic neuropathy that predisposes the lower extremities to repetitive injury and progressive tissue damage that may ultimately necessitate *** retinopathy(DR)is caused by cumulative damage to the retinal microvasculature from hyperglycemia and other diabetes-associated *** severity of DR is closely associated with the development of DFUs and the need for lower extremity revascularization procedures and/or *** the lower extremity,the eye may also suffer end-organ damage from macrovascular compromise in the form of cranial neuropathies that impair its motility,cause optic neuropathy,or result in partial or complete ***,poor perfusion of the eye can cause ischemic retinopathy leading to the development of proliferative diabetic retinopathy or neovascular glaucoma,both serious,visionthreatening ***,diabetic corneal ulcers and DFUs share many aspects of impaired wound healing resulting from neurovascular,sensory,and immunologic ***,alterations in serum biomarkers,such as hemoglobin A1c,ceruloplasmin,creatinine,low-density lipoprotein,and highdensity lipoprotein,are associated with both DR and *** these parameters can aid in prognosticating long-term outcomes and shed light on shared pathogenic mechanisms that lead to end-organ *** frequent cooccurrence of diabetic eye and foot problems mandate that patients affected by either condition undergo reciprocal comprehensive eye and foot evaluations in addition to optimizing diabetes management.

关键词： Foot ulcer Diabetic Wound healing Diabetes complications Amputation Diabetic retinopathy Corneal ulcer

Acute lower gastrointestinal bleeding from a dieulafoy lesion proximal to the anorectal junction post-orthotopic liver transplant

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World journal of Gastroenterology 2006年第46期12卷 7547-7548页

作者： Wichian Apiratpracha jin Kee Ho james j Powell Eric M Yoshida British Columbia Transplant Society The University of British Columbia Vancouver BC Canada Division of Gastroenterology Department of Medicine The University of British Columbia Vancouver BC Canada Department of Surgery The University of British Columbia Vancouver BC Canada

A 67-year-old woman underwent an orthotopic liver transplantation for end stage liver disease secondary to chronic autoimmune hepatitis. She developed sudden massive hematochezia on post-operative day 23 with hemodynamic compromise. The source of hemorrhage was found at colonoscopy after careful irrigation and inspection to be a dieulafoy lesion situated just proximal to the anorectal junction. Hemostasis was achieved with epinephrine injection and thermal coagulation.

关键词： Bleeding Anorectal Dieulafoy Rectum

3eciphering the protein-DNA code of bacteria Ninged helix-turn-helix transcription factors

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Frontiers of Electrical and Electronic Engineering in China 2018年第1期6卷 68-84页

作者： Adam P. joyce james j. Havranek Program in Developmental Regenerative and Stem Cell Biology Washington University in St. Louis St. Louis MO 63110 USA Department of Biochemistry and Molecular Biophysics Washington University in St. Louis St. Louis MO 63110 USA

Background： Sequence-specific binding by transcription factors （TFs） plays a significant role in the selection and regulation of target genes. At the protein：DNA interface, amino acid side-chains construct a diverse physicochemical network of specific and non-specific interactions, and seemingly subtle changes in amino acid identity at certain positions may dramatically impact TF：DNA binding. Variation of these specificity-determining residues （SDRs） is a major mechanism of functional divergence between TFs with strong structural or sequence homology. Methods： In this study, we employed a combination of high-throughput specificity profiling by SELEX and Spec-seq, structural modeling, and evolutionary analysis to probe the binding preferences of winged helix-turn-helix TFs belonging to the OmpR sub-family in Escherichia coil Results： We found that E. coli OmpR paralogs recognize tandem, variably spaced repeats composed of＂GT-A＂ or ＂GCT＂-containing half-sites. Some divergent sequence preferences observed within the ＂GT-A＂ mode correlate with amino acid similarity; conversely, ＂GCT＂-based motifs were observed for a subset of paralogs with low sequence homology. Direct specificity profiling of a subset of OmpR homologues （CpxR, RstA, and OmpR） as well as predicted ＂SDR-swap＂ variants revealed that individual SDRs may impact sequence preferences locally through direct contact with DNA bases or distally via the DNA backbone. Conclusions： Overall, our work provides evidence for a common structural code for sequence-specific wHTH：DNA interactions, and demonstrates that surprisingly modest residue changes can enable recognition of highly divergent sequence motifs. Further examination of SDR predictions will likely reveal additional mechanisms controlling the evolutionary divergence of this important class of transcriptional regulators.

关键词： transcription factor SELEX winged helix-turn-helix specificity detenlainants two-component signaling

The Shishugou Fauna of the Middle-Late jurassic Transition Period in the junggar Basin of Western China

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Acta Geologica Sinica(English Edition) 2022年第4期96卷 1115-1135页

作者： XU Xing james M.CLARK David A.EBERTH Philip j.CURRIE Centre for Vertebrate Evolutionary Biology Yunnan UniversityKunming 650500China Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China Department of Biological Sciences George Washington UniversityWashington DC20052USA Royal Tyrrell Museum of Palaeontology Box 7500DrumhellerAlberta T0J 0Y0Canada Department of Biological Sciences University of Alberta 116 Street and 85 AvenueEdmontonAB T6G 2R3Canada

The Middle-Late jurassic transition period is a critical period for the evolution of terrestrial vertebrates,but the global fossil record from this time is relatively *** Shishugou Fauna of this period has recently produced significant fossil remains of dinosaurs and other vertebrate groups,some representing the earliest known members of several dinosaurian groups and other vertebrate groups and some representing the best-known specimens of their *** discoveries are significant for our understanding of the origin and evolution of several vertebrate *** dating indicates that the fauna is aged approximately 159-164 *** with other similarly-aged terrestrial faunas such as Shaximiao and Yanliao show both taxonomic similarities and differences between these faunas and indicate that the junggar deposits might have preserved the most complete vertebrate fossil record for a Middle-Late jurassic Laurasian terrestrial fauna.

关键词： Middle-Late jurassic Shishugou Fauna Shishugou Formation terrestrial ecosystem Shaximiao Yanliao junggar Basin

Wing, tail, and vocal contributions to the complex acoustic signals of courting Calliope hummingbirds

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Current Zoology 2011年第2期57卷 187-196页

作者： Christopher james CLARK Peabody Museum of Natural History Yale University PO Box 208106 New Haven CT 06511 USA Museum of Vertebrate Zoology University of California- Berkeley Berkeley CA USA

Multi-component signals contain multiple signal parts expressed in the same physical modality. One way to identify individual components is if they are produced by different physical mechanisms. Here, I studied the mechanisms generating acoustic signals in the courtship displays of the Calliope hummingbird Stellula calliope. Display dives consisted of three synchronized sound elements, a high-frequency tone （hfl）, a low frequency tone （lft）, and atonal sound pulses （asp）, which were then followed by a frequency-modulated fall. Manipulating any of the rectrices （tail-feathers） of wild males impaired production of the lft and asp but not the hfl or fall, which are apparently vocal. I tested the sound production capabilities of the rectrices in a wind tunnel. Single rectrices could generate the lft but not the asp, whereas multiple rectrices tested together produced sounds sitlfilar to the asp when they fluttered and collided with their neighbors percussively, representing a previously unknown mechanism of sound production. During the shuttle display, a trill is generated by the wings during pulses in which the wingbeat frequency is elevated to 95 Hz, 40% higher than the typical hovering wingbeat frequency. The Calliope hummingbird courtship displays include sounds produced by three independent mechanisms, and thus include a minimum of three acoustic signal components. These acoustic mechanisms have different constraints and thus potentially contain different messages. Producing multiple acoustic signals via multiple mechanisms may be a way to escape the constraints present in any single mechanism .

关键词： Calliope Hummingbird Courtship Multicomponent Signal Sonation Wind Tunnel

Mice with a heterozygous Lrp6 deletion have impaired fracture healing

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Bone Research 2016年第2期4卷 101-109页

作者： Travis A Burgers juan F Vivanco juraj zahatnansky Andrew j Vander Moren james j Mason Bart O Williams Center for Cancer and Cell Biology Program for Skeletal Disease and Tumor Microenvironment Van Andel Research Institute Grand Rapids MhUSA Faculfad de Ingenieria y Ciencias Adolfo Ib6fiez University Vifia del Mar Chile padnos College of Engineering and Computing Grand Valley State University Grand Rapids MI USA

Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 （LRP6）, a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 （Lrp6~/-） and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6~^- mice and wild-type controls （Lrp6~/~）. Fractures were analyzed using micro-computed tomography （~CT） scans, biomechanical testing, and histological analysis. Lrp6~/- mice had significantly decreased stiffness and strength at 28 days post fracture （PF） and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.

关键词： bone Mice with a heterozygous Lrp6 deletion have impaired fracture healing