Jonathan S Marchant, Sandip Patel. Biochem Soc Trans 2015
Times Cited: 46
Times Cited: 46
Times Cited
Times Co-cited
Similarity
NAADP mobilizes calcium from acidic organelles through two-pore channels.
Peter J Calcraft, Margarida Ruas, Zui Pan, Xiaotong Cheng, Abdelilah Arredouani, Xuemei Hao, Jisen Tang, Katja Rietdorf, Lydia Teboul, Kai-Ting Chuang,[...]. Nature 2009
Peter J Calcraft, Margarida Ruas, Zui Pan, Xiaotong Cheng, Abdelilah Arredouani, Xuemei Hao, Jisen Tang, Katja Rietdorf, Lydia Teboul, Kai-Ting Chuang,[...]. Nature 2009
76
TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes.
Xiang Wang, Xiaoli Zhang, Xian-Ping Dong, Mohammad Samie, Xinran Li, Xiping Cheng, Andrew Goschka, Dongbiao Shen, Yandong Zhou, Janice Harlow,[...]. Cell 2012
Xiang Wang, Xiaoli Zhang, Xian-Ping Dong, Mohammad Samie, Xinran Li, Xiping Cheng, Andrew Goschka, Dongbiao Shen, Yandong Zhou, Janice Harlow,[...]. Cell 2012
67
Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.
Yasuteru Sakurai, Andrey A Kolokoltsov, Cheng-Chang Chen, Michael W Tidwell, William E Bauta, Norbert Klugbauer, Christian Grimm, Christian Wahl-Schott, Martin Biel, Robert A Davey. Science 2015
Yasuteru Sakurai, Andrey A Kolokoltsov, Cheng-Chang Chen, Michael W Tidwell, William E Bauta, Norbert Klugbauer, Christian Grimm, Christian Wahl-Schott, Martin Biel, Robert A Davey. Science 2015
58
Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling.
Eugen Brailoiu, Dev Churamani, Xinjiang Cai, Michael G Schrlau, G Cristina Brailoiu, Xin Gao, Robert Hooper, Michael J Boulware, Nae J Dun, Jonathan S Marchant,[...]. J Cell Biol 2009
Eugen Brailoiu, Dev Churamani, Xinjiang Cai, Michael G Schrlau, G Cristina Brailoiu, Xin Gao, Robert Hooper, Michael J Boulware, Nae J Dun, Jonathan S Marchant,[...]. J Cell Biol 2009
56
High susceptibility to fatty liver disease in two-pore channel 2-deficient mice.
Christian Grimm, Lesca M Holdt, Cheng-Chang Chen, Sami Hassan, Christoph Müller, Simone Jörs, Hartmut Cuny, Sandra Kissing, Bernd Schröder, Elisabeth Butz,[...]. Nat Commun 2014
Christian Grimm, Lesca M Holdt, Cheng-Chang Chen, Sami Hassan, Christoph Müller, Simone Jörs, Hartmut Cuny, Sandra Kissing, Bernd Schröder, Elisabeth Butz,[...]. Nat Commun 2014
54
mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.
Chunlei Cang, Yandong Zhou, Betsy Navarro, Young-Jun Seo, Kimberly Aranda, Lucy Shi, Shyuefang Battaglia-Hsu, Itzhak Nissim, David E Clapham, Dejian Ren. Cell 2013
Chunlei Cang, Yandong Zhou, Betsy Navarro, Young-Jun Seo, Kimberly Aranda, Lucy Shi, Shyuefang Battaglia-Hsu, Itzhak Nissim, David E Clapham, Dejian Ren. Cell 2013
54
The Two-pore channel (TPC) interactome unmasks isoform-specific roles for TPCs in endolysosomal morphology and cell pigmentation.
Yaping Lin-Moshier, Michael V Keebler, Robert Hooper, Michael J Boulware, Xiaolong Liu, Dev Churamani, Mary E Abood, Timothy F Walseth, Eugen Brailoiu, Sandip Patel,[...]. Proc Natl Acad Sci U S A 2014
Yaping Lin-Moshier, Michael V Keebler, Robert Hooper, Michael J Boulware, Xiaolong Liu, Dev Churamani, Mary E Abood, Timothy F Walseth, Eugen Brailoiu, Sandip Patel,[...]. Proc Natl Acad Sci U S A 2014
52
Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking.
Margarida Ruas, Katja Rietdorf, Abdelilah Arredouani, Lianne C Davis, Emyr Lloyd-Evans, Heidi Koegel, Timothy M Funnell, Anthony J Morgan, John A Ward, Keiko Watanabe,[...]. Curr Biol 2010
Margarida Ruas, Katja Rietdorf, Abdelilah Arredouani, Lianne C Davis, Emyr Lloyd-Evans, Heidi Koegel, Timothy M Funnell, Anthony J Morgan, John A Ward, Keiko Watanabe,[...]. Curr Biol 2010
47
Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition.
Leanne N Hockey, Bethan S Kilpatrick, Emily R Eden, Yaping Lin-Moshier, G Cristina Brailoiu, Eugen Brailoiu, Clare E Futter, Anthony H Schapira, Jonathan S Marchant, Sandip Patel. J Cell Sci 2015
Leanne N Hockey, Bethan S Kilpatrick, Emily R Eden, Yaping Lin-Moshier, G Cristina Brailoiu, Eugen Brailoiu, Clare E Futter, Anthony H Schapira, Jonathan S Marchant, Sandip Patel. J Cell Sci 2015
47
The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from lysosomal stores.
Xiangang Zong, Michael Schieder, Hartmut Cuny, Stefanie Fenske, Christian Gruner, Katrin Rötzer, Oliver Griesbeck, Hartmann Harz, Martin Biel, Christian Wahl-Schott. Pflugers Arch 2009
Xiangang Zong, Michael Schieder, Hartmut Cuny, Stefanie Fenske, Christian Gruner, Katrin Rötzer, Oliver Griesbeck, Hartmann Harz, Martin Biel, Christian Wahl-Schott. Pflugers Arch 2009
47
Convergent regulation of the lysosomal two-pore channel-2 by Mg²⁺, NAADP, PI(3,5)P₂ and multiple protein kinases.
Archana Jha, Malini Ahuja, Sandip Patel, Eugen Brailoiu, Shmuel Muallem. EMBO J 2014
Archana Jha, Malini Ahuja, Sandip Patel, Eugen Brailoiu, Shmuel Muallem. EMBO J 2014
43
Two-pore channels provide insight into the evolution of voltage-gated Ca2+ and Na+ channels.
Taufiq Rahman, Xinjiang Cai, G Cristina Brailoiu, Mary E Abood, Eugen Brailoiu, Sandip Patel. Sci Signal 2014
Taufiq Rahman, Xinjiang Cai, G Cristina Brailoiu, Mary E Abood, Eugen Brailoiu, Sandip Patel. Sci Signal 2014
41
An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.
Eugen Brailoiu, Taufiq Rahman, Dev Churamani, David L Prole, G Cristina Brailoiu, Robert Hooper, Colin W Taylor, Sandip Patel. J Biol Chem 2010
Eugen Brailoiu, Taufiq Rahman, Dev Churamani, David L Prole, G Cristina Brailoiu, Robert Hooper, Colin W Taylor, Sandip Patel. J Biol Chem 2010
41
Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells.
Margarida Ruas, Lianne C Davis, Cheng-Chang Chen, Anthony J Morgan, Kai-Ting Chuang, Timothy F Walseth, Christian Grimm, Clive Garnham, Trevor Powell, Nick Platt,[...]. EMBO J 2015
Margarida Ruas, Lianne C Davis, Cheng-Chang Chen, Anthony J Morgan, Kai-Ting Chuang, Timothy F Walseth, Christian Grimm, Clive Garnham, Trevor Powell, Nick Platt,[...]. EMBO J 2015
36
Photoaffinity labeling of nicotinic acid adenine dinucleotide phosphate (NAADP) targets in mammalian cells.
Yaping Lin-Moshier, Timothy F Walseth, Dev Churamani, Sean M Davidson, James T Slama, Robert Hooper, Eugen Brailoiu, Sandip Patel, Jonathan S Marchant. J Biol Chem 2012
Yaping Lin-Moshier, Timothy F Walseth, Dev Churamani, Sean M Davidson, James T Slama, Robert Hooper, Eugen Brailoiu, Sandip Patel, Jonathan S Marchant. J Biol Chem 2012
34
The voltage-gated sodium channel TPC1 confers endolysosomal excitability.
Chunlei Cang, Biruk Bekele, Dejian Ren. Nat Chem Biol 2014
Chunlei Cang, Biruk Bekele, Dejian Ren. Nat Chem Biol 2014
32
NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs.
Grant C Churchill, Yuhei Okada, Justyn M Thomas, Armando A Genazzani, Sandip Patel, Antony Galione. Cell 2002
Grant C Churchill, Yuhei Okada, Justyn M Thomas, Armando A Genazzani, Sandip Patel, Antony Galione. Cell 2002
30
Photoaffinity labeling of high affinity nicotinic acid adenine dinucleotide phosphate (NAADP)-binding proteins in sea urchin egg.
Timothy F Walseth, Yaping Lin-Moshier, Pooja Jain, Margarida Ruas, John Parrington, Antony Galione, Jonathan S Marchant, James T Slama. J Biol Chem 2012
Timothy F Walseth, Yaping Lin-Moshier, Pooja Jain, Margarida Ruas, John Parrington, Antony Galione, Jonathan S Marchant, James T Slama. J Biol Chem 2012
30
PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome.
Xian-ping Dong, Dongbiao Shen, Xiang Wang, Taylor Dawson, Xinran Li, Qi Zhang, Xiping Cheng, Yanling Zhang, Lois S Weisman, Markus Delling,[...]. Nat Commun 2010
Xian-ping Dong, Dongbiao Shen, Xiang Wang, Taylor Dawson, Xinran Li, Qi Zhang, Xiping Cheng, Yanling Zhang, Lois S Weisman, Markus Delling,[...]. Nat Commun 2010
28
TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+.
Samantha J Pitt, Tim M Funnell, Mano Sitsapesan, Elisa Venturi, Katja Rietdorf, Margarida Ruas, A Ganesan, Rajendra Gosain, Grant C Churchill, Michael X Zhu,[...]. J Biol Chem 2010
Samantha J Pitt, Tim M Funnell, Mano Sitsapesan, Elisa Venturi, Katja Rietdorf, Margarida Ruas, A Ganesan, Rajendra Gosain, Grant C Churchill, Michael X Zhu,[...]. J Biol Chem 2010
28
Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release.
Dongbiao Shen, Xiang Wang, Xinran Li, Xiaoli Zhang, Zepeng Yao, Shannon Dibble, Xian-ping Dong, Ting Yu, Andrew P Lieberman, Hollis D Showalter,[...]. Nat Commun 2012
Dongbiao Shen, Xiang Wang, Xinran Li, Xiaoli Zhang, Zepeng Yao, Shannon Dibble, Xian-ping Dong, Ting Yu, Andrew P Lieberman, Hollis D Showalter,[...]. Nat Commun 2012
26
An ancestral deuterostome family of two-pore channels mediates nicotinic acid adenine dinucleotide phosphate-dependent calcium release from acidic organelles.
Eugen Brailoiu, Robert Hooper, Xinjiang Cai, G Cristina Brailoiu, Michael V Keebler, Nae J Dun, Jonathan S Marchant, Sandip Patel. J Biol Chem 2010
Eugen Brailoiu, Robert Hooper, Xinjiang Cai, G Cristina Brailoiu, Michael V Keebler, Nae J Dun, Jonathan S Marchant, Sandip Patel. J Biol Chem 2010
26
Degeneration of an intracellular ion channel in the primate lineage by relaxation of selective constraints.
Xinjiang Cai, Sandip Patel. Mol Biol Evol 2010
Xinjiang Cai, Sandip Patel. Mol Biol Evol 2010
26
TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.
Margarida Ruas, Kai-Ting Chuang, Lianne C Davis, Areej Al-Douri, Patricia W Tynan, Ruth Tunn, Lydia Teboul, Antony Galione, John Parrington. Mol Cell Biol 2014
Margarida Ruas, Kai-Ting Chuang, Lianne C Davis, Areej Al-Douri, Patricia W Tynan, Ruth Tunn, Lydia Teboul, Antony Galione, John Parrington. Mol Cell Biol 2014
26
Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates autophagy in cultured astrocytes.
Gustavo J S Pereira, Hanako Hirata, Gian M Fimia, Lúcia G do Carmo, Claudia Bincoletto, Sang W Han, Roberta S Stilhano, Rodrigo P Ureshino, Duncan Bloor-Young, Grant Churchill,[...]. J Biol Chem 2011
Gustavo J S Pereira, Hanako Hirata, Gian M Fimia, Lúcia G do Carmo, Claudia Bincoletto, Sang W Han, Roberta S Stilhano, Rodrigo P Ureshino, Duncan Bloor-Young, Grant Churchill,[...]. J Biol Chem 2011
26
VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling.
Annarita Favia, Marianna Desideri, Guido Gambara, Alessio D'Alessio, Margarida Ruas, Bianca Esposito, Donatella Del Bufalo, John Parrington, Elio Ziparo, Fioretta Palombi,[...]. Proc Natl Acad Sci U S A 2014
Annarita Favia, Marianna Desideri, Guido Gambara, Alessio D'Alessio, Margarida Ruas, Bianca Esposito, Donatella Del Bufalo, John Parrington, Elio Ziparo, Fioretta Palombi,[...]. Proc Natl Acad Sci U S A 2014
26
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB.
Diego L Medina, Simone Di Paola, Ivana Peluso, Andrea Armani, Diego De Stefani, Rossella Venditti, Sandro Montefusco, Anna Scotto-Rosato, Carolina Prezioso, Alison Forrester,[...]. Nat Cell Biol 2015
Diego L Medina, Simone Di Paola, Ivana Peluso, Andrea Armani, Diego De Stefani, Rossella Venditti, Sandro Montefusco, Anna Scotto-Rosato, Carolina Prezioso, Alison Forrester,[...]. Nat Cell Biol 2015
26
An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling.
Bethan S Kilpatrick, Emily R Eden, Leanne N Hockey, Elizabeth Yates, Clare E Futter, Sandip Patel. Cell Rep 2017
Bethan S Kilpatrick, Emily R Eden, Leanne N Hockey, Elizabeth Yates, Clare E Futter, Sandip Patel. Cell Rep 2017
26
Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals.
Bethan S Kilpatrick, Emily R Eden, Anthony H Schapira, Clare E Futter, Sandip Patel. J Cell Sci 2013
Bethan S Kilpatrick, Emily R Eden, Anthony H Schapira, Clare E Futter, Sandip Patel. J Cell Sci 2013
23
Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP.
Patricia Gómez-Suaga, Berta Luzón-Toro, Dev Churamani, Ling Zhang, Duncan Bloor-Young, Sandip Patel, Philip G Woodman, Grant C Churchill, Sabine Hilfiker. Hum Mol Genet 2012
Patricia Gómez-Suaga, Berta Luzón-Toro, Dev Churamani, Ling Zhang, Duncan Bloor-Young, Sandip Patel, Philip G Woodman, Grant C Churchill, Sabine Hilfiker. Hum Mol Genet 2012
23
Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease.
Anthony J Morgan, Frances M Platt, Emyr Lloyd-Evans, Antony Galione. Biochem J 2011
Anthony J Morgan, Frances M Platt, Emyr Lloyd-Evans, Antony Galione. Biochem J 2011
23
NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system.
Gihan S Gunaratne, Yang Yang, Fang Li, Timothy F Walseth, Jonathan S Marchant. Cell Calcium 2018
Gihan S Gunaratne, Yang Yang, Fang Li, Timothy F Walseth, Jonathan S Marchant. Cell Calcium 2018
23
Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function.
Susanne Gerndt, Cheng-Chang Chen, Yu-Kai Chao, Yu Yuan, Sandra Burgstaller, Anna Scotto Rosato, Einar Krogsaeter, Nicole Urban, Katharina Jacob, Ong Nam Phuong Nguyen,[...]. Elife 2020
Susanne Gerndt, Cheng-Chang Chen, Yu-Kai Chao, Yu Yuan, Sandra Burgstaller, Anna Scotto Rosato, Einar Krogsaeter, Nicole Urban, Katharina Jacob, Ong Nam Phuong Nguyen,[...]. Elife 2020
23
pH-dependent regulation of lysosomal calcium in macrophages.
Kenneth A Christensen, Jesse T Myers, Joel A Swanson. J Cell Sci 2002
Kenneth A Christensen, Jesse T Myers, Joel A Swanson. J Cell Sci 2002
21
Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium.
Emyr Lloyd-Evans, Anthony J Morgan, Xingxuan He, David A Smith, Elena Elliot-Smith, Daniel J Sillence, Grant C Churchill, Edward H Schuchman, Antony Galione, Frances M Platt. Nat Med 2008
Emyr Lloyd-Evans, Anthony J Morgan, Xingxuan He, David A Smith, Elena Elliot-Smith, Daniel J Sillence, Grant C Churchill, Edward H Schuchman, Antony Galione, Frances M Platt. Nat Med 2008
21
Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling.
Sandip Patel, Roberto Docampo. Trends Cell Biol 2010
Sandip Patel, Roberto Docampo. Trends Cell Biol 2010
21
Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+.
Samantha J Pitt, Andy K M Lam, Katja Rietdorf, Antony Galione, Rebecca Sitsapesan. Sci Signal 2014
Samantha J Pitt, Andy K M Lam, Katja Rietdorf, Antony Galione, Rebecca Sitsapesan. Sci Signal 2014
21
NAADP activates two-pore channels on T cell cytolytic granules to stimulate exocytosis and killing.
Lianne C Davis, Anthony J Morgan, Ji-Li Chen, Charlotte M Snead, Duncan Bloor-Young, Eugene Shenderov, Megan N Stanton-Humphreys, Stuart J Conway, Grant C Churchill, John Parrington,[...]. Curr Biol 2012
Lianne C Davis, Anthony J Morgan, Ji-Li Chen, Charlotte M Snead, Duncan Bloor-Young, Eugene Shenderov, Megan N Stanton-Humphreys, Stuart J Conway, Grant C Churchill, John Parrington,[...]. Curr Biol 2012
21
Characterization of two-pore channel 2 (TPCN2)-mediated Ca2+ currents in isolated lysosomes.
Michael Schieder, Katrin Rötzer, Andrea Brüggemann, Martin Biel, Christian A Wahl-Schott. J Biol Chem 2010
Michael Schieder, Katrin Rötzer, Andrea Brüggemann, Martin Biel, Christian A Wahl-Schott. J Biol Chem 2010
21
Membrane potential regulates nicotinic acid adenine dinucleotide phosphate (NAADP) dependence of the pH- and Ca2+-sensitive organellar two-pore channel TPC1.
Volodymyr Rybalchenko, Malini Ahuja, Jessica Coblentz, Dev Churamani, Sandip Patel, Krill Kiselyov, Shmuel Muallem. J Biol Chem 2012
Volodymyr Rybalchenko, Malini Ahuja, Jessica Coblentz, Dev Churamani, Sandip Patel, Krill Kiselyov, Shmuel Muallem. J Biol Chem 2012
21
A non-inactivating high-voltage-activated two-pore Na⁺ channel that supports ultra-long action potentials and membrane bistability.
Chunlei Cang, Kimberly Aranda, Dejian Ren. Nat Commun 2014
Chunlei Cang, Kimberly Aranda, Dejian Ren. Nat Commun 2014
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Lysosomal two-pore channel subtype 2 (TPC2) regulates skeletal muscle autophagic signaling.
Pei-Hui Lin, Pu Duann, Shinji Komazaki, Ki Ho Park, Haichang Li, Mingzhai Sun, Mathew Sermersheim, Kristyn Gumpper, John Parrington, Antony Galione,[...]. J Biol Chem 2015
Pei-Hui Lin, Pu Duann, Shinji Komazaki, Ki Ho Park, Haichang Li, Mingzhai Sun, Mathew Sermersheim, Kristyn Gumpper, John Parrington, Antony Galione,[...]. J Biol Chem 2015
21
The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.
Xian-Ping Dong, Xiping Cheng, Eric Mills, Markus Delling, Fudi Wang, Tino Kurz, Haoxing Xu. Nature 2008
Xian-Ping Dong, Xiping Cheng, Eric Mills, Markus Delling, Fudi Wang, Tino Kurz, Haoxing Xu. Nature 2008
21
A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation.
Xinran Li, Nicholas Rydzewski, Ahmad Hider, Xiaoli Zhang, Junsheng Yang, Wuyang Wang, Qiong Gao, Xiping Cheng, Haoxing Xu. Nat Cell Biol 2016
Xinran Li, Nicholas Rydzewski, Ahmad Hider, Xiaoli Zhang, Junsheng Yang, Wuyang Wang, Qiong Gao, Xiping Cheng, Haoxing Xu. Nat Cell Biol 2016
21
Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.
Ji She, Jiangtao Guo, Qingfeng Chen, Weizhong Zeng, Youxing Jiang, Xiao-Chen Bai. Nature 2018
Ji She, Jiangtao Guo, Qingfeng Chen, Weizhong Zeng, Youxing Jiang, Xiao-Chen Bai. Nature 2018
21
Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells.
J M Cancela, G C Churchill, A Galione. Nature 1999
J M Cancela, G C Churchill, A Galione. Nature 1999
19
The role of intraorganellar Ca(2+) in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles.
P R Pryor, B M Mullock, N A Bright, S R Gray, J P Luzio. J Cell Biol 2000
P R Pryor, B M Mullock, N A Bright, S R Gray, J P Luzio. J Cell Biol 2000
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Lysosomes: fusion and function.
J Paul Luzio, Paul R Pryor, Nicholas A Bright. Nat Rev Mol Cell Biol 2007
J Paul Luzio, Paul R Pryor, Nicholas A Bright. Nat Rev Mol Cell Biol 2007
19
Co-cited is the co-citation frequency, indicating how many articles cite the article together with the query article. Similarity is the co-citation as percentage of the times cited of the query article or the article in the search results, whichever is the lowest. These numbers are calculated for the last 100 citations when articles are cited more than 100 times.