-
作者:Kuhn, Hunter W.; Smither, Madeleine R.; Jin, Rachel J.; Collins, Christina A.; Ma, Hongming; Sina, Jason; Gaut, Joseph P.; Diamond, Michael S.; Hunstad, David A.
作者单位:Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
摘要:The alpha- hemolysin (HlyA) of uropathogenic Escherichia coli (UPEC) is a pore-forming toxin (PFT) that is thought to function by disrupting the host cell plasma membrane. Although CD18 (LFA-1) has been implicated as a receptor on myeloid cells, the mechanisms underlying HlyA cytotoxicity to epithelial cells are poorly defined. Here, we show that HlyA secretion by UPEC markedly intensifies renal tubular epithelial injury in a murine model of ascending pyelonephritis. A CRISPR-Cas9 loss-of-func...
-
作者:Nesbitt, Jason
作者单位:Tulane University
-
作者:Toomey, Christopher B.; Pflugmacher, Savanna; Park, Kamalu; Pihl, Jessica; Novak, Sammy Weiser; Rodriguez, Jessica; Jalali, Maryam; Jung, Jaesoo; Mozafari, Madeline; Omran, Sima P.; Pormir, Cameron K.; Hauer, Jill; Painter, Chelsea; Walker, Evan; Huang, Alex S.; Boassa, Daniela; Handa, James T.; Aastrup, Teodor; Gordts, Philip L. S. M.; Esko, Jeffrey D.
作者单位:University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Salk Institute; Johns Hopkins University; Johns Hopkins Medicine; University of California System; University of California San Diego
摘要:Lipoprotein retention in Bruch's membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. Given the established role of glycosaminoglycans (GAG) in binding lipoproteins, our laboratory sought to determine the role of GAGs in AMD BrM. In this study, BrM GAG content in AMD pathobiology was analyzed in human postmortem tissue. Strikingly, increased levels of highly sulfated hepa...
-
作者:Yuan, Xueying; Yan, Lu; Chen, Qinfu; Zhu, Shukai; Zhou, Xinyu; Zeng, Ling-Hui; Liu, Mingjie; He, Xiaojing; Huang, Jun; Lu, Weiguo; Zhang, Long; Yan, Haiyan; Wang, Fangwei
-
作者:Zhao, Yue; Zhang, Keren; Li, Guo; Wang, Yuming; Ding, Xiaoyang; Wang, Shuo; Pang, Xi; Zhao, Xueru; Yu, Yue; Liu, Jiaqi; Yu, Tingting; Bao, Guixian; Wang, Tianya; Ni, Zhongfu; Xin, Mingming; Liu, Bao; Wendel, Jonathan F.; Zhang, Zhibin; Gong, Lei
作者单位:Northeast Normal University - China; Jilin Academy of Agricultural Sciences; China Agricultural University; China Agricultural University; Iowa State University
摘要:The union of two or more different nuclear genomes with maternally inherited organellar genomes may lead to cytonuclear incompatibilities in plant allopolyploids. These incompatibilities may be reconciled by coevolutionary responses at the genomic and transcriptional levels. To date, the relationship between extent of divergence among parental organellar genomes and cytonuclear coevolutionary responses remains largely unexplored. Here, we studied transcriptional cytonuclear expression in synth...
-
作者:Ricciardi, Adele S.; Barone, Christina; Putman, Rachael; Quijano, Elias; Gupta, Anisha; Nguyen, Richard; Mandl, Hanna; Piotrowski-Daspit, Alexandra S.; Lopez-Giraldez, Francesc; Luks, Valerie; Freedman-Weiss, Mollie R.; Farrelly, James; Ahle, Samantha; Lynn, Anna Y.; Glazer, Peter M.; Saltzman, W. Mark; Stitelman, David H.; Egan, Marie E.
作者单位:Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University
摘要:In utero gene editing has the potential to modify disease- causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. Thus, treating CF...
-
作者:Zheng, Xianyao; Wu, Shuaishuai; Qiu, Jiangbing; Li, Aifeng; Li, Ling; Yan, Guowang; Li, Min; Meng, Fanping; Zhang, Kaidian; Lin, Senjie
作者单位:Hainan University; Ocean University of China; Ocean University of China; Xiamen University; University of Connecticut
摘要:The beta- N- methylamino- L- alanine (BMAA) is an emerging neurotoxin associated with human neurodegenerative diseases such as Alzheimer's disease. Here, we report the prevalence of BMAA synthesis in protein forms by marine diatoms and reconstruct its tentative biosynthesis pathway. Remarkably, the BMAA production is strongly induced by iron limitation. Transcriptomic analyses suggest that cysteine synthase (CysK) is involved in BMAA synthesis. This is verified as CRISPR/Cas9- based CysK knock...
-
作者:Kalle, Anagha; Wu, Jian; Tawfeeq, Caesar; Kornev, Alexandr P.; Veglia, Gianluigi; Maillard, Rodrigo; Taylor, Susan S.; Jonniya, Nisha Amarnath
作者单位:Johns Hopkins University; University of California System; University of California San Diego; University of California System; University of California San Diego; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Georgetown University; Georgetown University; National Institute of Technology (NIT System); National Institute of Technology Andhra Pradesh
摘要:Cushing's syndrome (CS) is an abnormal condition characterized by elevated cortisol levels, often resulting from genetic alterations in the PRKACA gene, which encodes the catalytic subunit of cAMP-dependent protein kinase A (PKA-C). The most common CS mutation, L205R, lies at the P + 1 loop. Understanding how this mutation alters the internal allosteric network within PKA-C and changes nucleotide and substrate cooperativity is a major goal. Using molecular dynamics (MD) simulations and protein...
-
作者:Meirmans, Patrick G.; Kolar, Filip
作者单位:University of Amsterdam; Charles University Prague; Czech Academy of Sciences; Institute of Botany of the Czech Academy of Sciences
摘要:Polyploidization (whole-genome duplication, WGD) is a widespread large-effect macromutation with far-reaching genomic, phenotypic, and evolutionary consequences. Yet, we do not know whether the consistent phenotypic changes that are associated with polyploidization translate into predictable changes in ecological preferences. Niche modeling studies in mixed-ploidy species provide an opportunity to compare recently originated polyploids with their lower-ploidy ancestors. However, the available ...
-
作者:Palomero, Orhi Esarte; Guadarrama, Eduardo; DeCaen, Paul G.
作者单位:Northwestern University; Feinberg School of Medicine; Northwestern University
摘要:PKD2 is a member of the polycystin subfamily of transient receptor potential (TRP) ion channel subunits which traffic and function in primary cilia organelle membranes. Millions of individuals carry pathogenic genetic variants in PKD2 that cause a life-threatening condition called autosomal dominant polycystic kidney disease (ADPKD). Although ADPKD is a common monogenetic disorder, there is no drug cure or available therapeutics which address the underlying channel dysregulation. Furthermore, ...