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

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

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Small GTPases and cilia

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Protein & Cell 2011年第3期2卷 13-25页

作者： Yujie Li jinghua hu Department of Nephrology and hypertension Mayo ClinicRochesterMinnesotaUSA Translational PKD Center Mayo ClinicRochesterMinnesotaUSA Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMinnesotaUSA

Small GTPases are key molecular switches that bind and hydrolyze GTP in diverse membrane-and cytoskeletonrelated cellular ***,mounting evidences have highlighted the role of various small GTPases,including the members in Arf/Arl,Rab,and Ran subfamilies,in cilia formation and *** overlooked as an evolutionary vestige,the primary cilium has attracted more and more attention in last decade because of its role in sensing various extracellular signals and the association between cilia dysfunction and a wide spectrum of human diseases,now called *** we review recent advances about the function of small GTPases in the context of cilia,and the correlation between the functional impairment of small GTPases and *** of these cellular processes is of fundamental importance for broadening our view of cilia development and function in normal and pathological states and for providing valuable insights into the role of various small GTPases in disease processes,and their potential as therapeutic targets.

关键词： Small GTPase cilia ciliopathy

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Lineage structure of the human antibody repertoire in response to influenza vaccination

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医用生物力学 2013年第S1期28卷 36-37页

作者： Ning jiang jiankui he joshua A.Weinstein Lolita Penland Sanae Sasaki Xiao-Song he Patrick C.Wilson harry B.Greenberg Mark M.Davis Daniel S.Fisher Stephen R.Quake Department of Biomedical Engineering the University of Texas at AustinAustinTXUSA Department of Bioengineering Stanford University School of MedicineStanfordCaliforniaUSA Biophysics Graduate Program Stanford UniversityStanfordCaliforniaUSA Department of Immunology and Microbiology Stanford University School of MedicineStanfordCaliforniaUSA VA Palo Alto health Care System Palo AltoCaliforniaUSA Department of Medicine Stanford University School of MedicineStanfordCaliforniaUSA Department of Medicine University of Chicago Pritzker School of MedicineChicagoIllinoisUSA howard hughes Medical Institute Department of Applied Physics Stanford UniversityStanfordCaliforniaUSA Department of Biology Stanford UniversityStanfordCaliforniaUSA

The adaptive immune system produces a large and diverse set of antibodies,each with an individual evolutionary and clonal *** so called"antibody repertoire"protects each individual against insults such as infection and cancer,and responds to vaccination with B cell proliferation in response to the antigenic *** and antigen-specific FACSbased analysis have given us much insight on how the immune system generates the complex and diverse immune response required to protect the body from the wide variety of potential ***,these methods have not been sufficient to make global and unbiased characterizations of the clonal structure of the immune system of a particular individual。

关键词： vaccination clonal antigenic diverse insight stimulation evolutionary immunized protect vaccine

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Dietary fatty acids and bioactive fatty acid metabolites in alcoholic liver disease

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Liver Research 2019年第3期3卷 206-217页

作者： Kara h.Zirnheld Dennis R.Warner jeffrey B.Warner josiah E.hardesty Craig j.McClain Irina A.Kirpich Division of Gastroenterology Hepatologyand NutritionDepartment of MedicineUniversity of Louisville School of MedicineLouisvilleKYUSA Department of Pharmacology and Toxicology University of Louisville School of MedicineLouisvilleKYUSA University of Louisville Alcohol Center University of Louisville School of MedicineLouisvilleKYUSA Robley Rex Veterans Medical Center LouisvilleKYUSA

Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and *** work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully *** rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA *** is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFAderived lipid molecules in *** that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this *** current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.

关键词： Dietary fatty acids Bioactive fatty acid metabolites Alcoholic liver disease(ALD) Omega-6 polyunsaturated fatty acids(n-6 PUFAs) Omega-3 polyunsaturated fatty acids(n-3 PUFAs)

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LiF@SiO2 nanocapsules for controlled lithium release and osteoarthritis treatment

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Nano Research 2018年第10期11卷 5751-5760页

作者： Trever Todd Zhenhui Lu jinmin Zhao Benjamin Cline Weizhong Zhang hongmin Chen Anil Kumar Wen jiang Franklin West Samuel Franklin Li Zheng jin Xie Department of Chemistry University of Georgia Athens Georgia 30602 USA Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration Guangxi Collaborative Innovation Center for Biomedicine Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical University Nanning 530021 China Center for Molecular Imaging and Translational Medicine State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public Health Xiamen University Xiamen 361102 China Animal Dairy Science University of Georgia Athens Georgia 30602 USA Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens Georgia 30602 USA

Electrolytes can be taken orally or intravenously as supplements or thera- peutics. however, their therapeutic window may exceed the serum toxicity threshold, making systemic delivery a poor option. Local injection is also not adequate due to rapid diffusion of electrolytes. here, we solved this issue with a nanocapsule technolog~ comprising an electrolyte nanocrystal as the drug filling and a silica sheath to regulate drug release rates. In particular, we prepared LiF@SiO2 nanocapsules and investigated their potential as a delivery system for lithium, which was shown in recent studies to be an effective therapeutic agent for osteoarthritis （OA）. We demonstrated that LiF@SiO2 can extend lithium release time from minutes to more than 60 h. After intra- articular （i.a.） injection into a rat OA model, the nanocapsules reduced the Osteoarthritis Research Society International （OARSI） score by 71% in 8 weeks while inducing no systemic toxicity. Our study opens new doors for improved delivery of electrolyte therapeutics, which have rarely been studied in the past.

关键词： osteoarthrifis controlled release hyaluronic acid lithium anti-inflammation

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Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function

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Cellular & Molecular Immunology 2021年第2期18卷 328-338页

作者： juan huang jian Peng james Alexander Pearson Georgios Efthimiou Youjia hu Ningwen Tai Yanpeng Xing Luyao Zhang jianlei Gu jianping jiang hongyu Zhao Zhiguang Zhou F.Susan Wong Li Wen national Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology(Central South University)Ministry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina Section of Endocrinology Department of Internal MedicineSchool of MedicineYale UniversityNew HavenCTUSA Division of Infection and Immunity School of MedicineCardiff UniversityCardiffUK Department of Microbiology University of HullHullUK Department of Gastrointestinal Surgery of the First hospital of jilin University ChangchunJilinChina Department of Biostatistics Data Science&GeneticsYale School of Public HealthNew HavenCTUSA

Innate immunity mediated by Toll-like receptors(TLRs),which can recognize pathogen molecular patterns,plays a critical role in type 1 diabetes ***7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells;however,its role in type 1 diabetes development remains *** our study,we discovered that Tlr7-deficient(Tlr7^(−/−))nonobese diabetic(NOD)mice,a model of human type 1 diabetes,exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient(Tlr7^(+/+))NOD *** investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin ***,Tlr7^(−/−)NOD B cells were found to suppress diabetogenic CD4^(+)T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T *** addition,we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8^(+)T-cell activation by downregulating the expression of both nonclassical and classical MhC class I(MhC-I)molecules on B *** data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T ***,therapeutically targeting TLR7 may prove beneficial for disease protection.

关键词： Type 1 diabetes Toll-like receptor 7 B cell

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肝细胞癌的代谢改变及代谢弱点

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Gastroenterology Report 2021年第1期9卷 1-13,I0001页

作者： Daniel GTenen Li Chai justin L.Tan Cancer Science Institute of Singapore National University of SingaporeSingapore harvard Stem Cell Institute Harvard Medical SchoolBostonMAUSA Department of Pathology Brigham&Women’s HospitalHarvard Medical SchoolBostonMAUSA Experimental Drug Development Centre Agency for ScienceTechnology and Research(A*STAR)Singapore Genome Institute of Singapore Agency for ScienceTechnology and Research(A*STAR)Singapore

肝癌是一种严重的疾病,全球死亡率高居癌症第二位。肝细胞癌(hCC)源于转化的肝细胞,是肝癌的主要类型,占全部肝癌病例的85%。hCC代谢是目前的研究热点之一。肝脏是体内许多代谢过程的主要场所,研究表明,与正常肝细胞相比,hCC细胞代谢严... 详细信息

肝癌是一种严重的疾病,全球死亡率高居癌症第二位。肝细胞癌(hCC)源于转化的肝细胞,是肝癌的主要类型,占全部肝癌病例的85%。hCC代谢是目前的研究热点之一。肝脏是体内许多代谢过程的主要场所,研究表明,与正常肝细胞相比,hCC细胞代谢严重紊乱。因此,深入理解hCC引起的代谢变化及其机制至关重要,有助于提高hCC的诊治水平。在这篇综述中,我们对hCC代谢改变、代谢弱点及潜在治疗措施进行文献总结。

关键词： hepatocellular carcinoma(hCC) metabolism metabolic vulnerability targeted therapy

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high-Frequency 3D Photoacoustic Computed Tomography Using an Optical Microring Resonator

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Biomedical Engineering Frontiers 2022年第1期3卷 348-355页

作者： Qiangzhou Rong Youngseop Lee Yuqi Tang Tri Vu Carlos Taboada Wenhan Zheng jun Xia David A.Czaplewski hao F.Zhang Cheng Sun junjie Yao Department of Biomedical Engineering Duke UniversityDurhamNCUSA 27708 Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Mechanical Engineering Northwestern UniversityEvanstonIL 60208USA Optical&Ultrasonic Imaging Laboratory University at BuffaloNorth Campus BuffaloNY 14260USA Center for Nanoscale Materials Argonne National LaboratoryArgonneIL 60439USA

3D photoacoustic computed tomography(3D-PACT)has made great advances in volumetric imaging of biological tissues,with high spatial-temporal resolutions and large penetration *** development of 3D-PACT requires high-performance acoustic sensors with a small size,large detection bandwidth,and high *** this work,we present a new high-frequency 3D-PACT system that uses a microring resonator(MRR)as the acoustic *** MRR sensor has a size of 80μm in diameter and was fabricated using the nanoimprint lithography *** the MRR sensor,we have developed a transmission-mode 3D-PACT system that has achieved a detection bandwidth of~23 Mhz,an imaging depth of~8 mm,a lateral resolution of 114μm,and an axial resolution of 57μ*** have demonstrated the 3D PACT’s performance on in vitro phantoms,ex vivo mouse brain,and in vivo mouse ear and *** MRR-based 3D-PACT system can be a promising tool for structural,functional,and molecular imaging of biological tissues at depths.

关键词： resonator lithography resolution

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Label-free SARS-CoV-2 detection and classification using phase imaging with computational specificity

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Light(Science & Applications) 2021年第9期10卷 1797-1808页

作者： Neha Goswami Yuchen R.he Yu-heng Deng Chamteut Oh Nahil Sobh Enrique Valera Rashid Bashir Nahed Ismail hyunjoon Kong Thanh h.Nguyen Catherine Best-Popescu Gabriel Popescu Department of Bioengineering University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Beckman Institute of Advanced Science and Technology University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Department of Electrical and Computer Engineering University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Department of Chemical and Biomolecular Engineering University of Illinois at Urbana-ChampaignUrbanaIL61801USA Department of Civil and Environmental Engineering University of Illinois at Urbana-ChampaignUrbanaIL61801USA NCSA Center for Artificial Intelligence Innovation University of Illinois at Urbana-ChampaignUrbanaIL61801USA holonyak Micro and Nanotechnology Laboratory University of Illinois at Urbana-ChampaignUrbanaIllinois61801USA Biomedical Research Center Carle Foundation Hospital509W University Ave.UrbanaIllinois61801USA Carle Illinois College of Medicine 807 South Wright St.UrbanaIllinois61801USA Mayo-Illinois Alliance for Technology Based healthcare UrbanaIllinois61801USA Department of Pathology College of MedicineUniversity of Illinois at ChicagoChicagoILUSA

Efforts to mitigate the COVID-19 crisis revealed that fast,accurate,and scalable testing is crucial for curbing the current impact and that of future *** propose an optical method for directly imaging unlabeled viral particles and using deep learning for detection and *** ultrasensitive interferometric method was used to image four virus types with nanoscale optical path-length *** these data with fluorescence images for ground truth,we trained semantic segmentation models based on U-Net,a particular type of convolutional neural *** trained network was applied to classify the viruses from the interferometric images only,containing simultaneously SARS-CoV-2,h1N1(influenza-A virus),hAdV(adenovirus),and ZIKV(Zika virus).Remarkably,due to the nanoscale sensitivity in the input data,the neural network was able to identify SARS-CoV-2 *** other viruses with 96%*** inference time for each image is 60 ms,on a common graphic-processing *** approach of directly imaging unlabeled viral particles may provide an extremely fast test,of less than a minute per *** the imaging instrument operates on regular glass slides,we envision this method as potentially testing on patient breath *** necessary high throughput can be achieved by translating concepts from digital pathology,where a microscope can scan hundreds of slides automatically.

关键词： testing neural hundreds

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