@article{Escolar-Peña2024,

title = {Specific microRNA Profile Associated with Inflammation and Lipid Metabolism for Stratifying Allergic Asthma Severity},

author = {Andrea Escolar-Peña and María Isabel Delgado-Dolset and Carmela Pablo-Torres and Carlos Tarin and Leticia Mera-Berriatua and María del Pilar Cuesta Apausa and Heleia González Cuervo and Rinku Sharma and Alvin T. Kho and Kelan G. Tantisira and Michael J. McGeachie and Rocio Rebollido-Rios and Domingo Barber and Teresa Carrillo and Elena Izquierdo and María M. Escribese},

doi = {10.3390/ijms25179425},

issn = {1422-0067},

year  = {2024},

date = {2024-09-00},

urldate = {2024-09-00},

journal = {IJMS},

volume = {25},

number = {17},

publisher = {MDPI AG},

abstract = {<jats:p>The mechanisms underlying severe allergic asthma are complex and unknown, meaning it is a challenge to provide the most appropriate treatment. This study aimed to identify novel biomarkers for stratifying allergic asthmatic patients according to severity, and to uncover the biological mechanisms that lead to the development of the severe uncontrolled phenotype. By using miRNA PCR panels, we analyzed the expression of 752 miRNAs in serum samples from control subjects (n = 15) and mild (n = 11) and severe uncontrolled (n = 10) allergic asthmatic patients. We identified 40 differentially expressed miRNAs between severe uncontrolled and mild allergic asthmatic patients. Functional enrichment analysis revealed signatures related to inflammation, angiogenesis, lipid metabolism and mRNA regulation. A random forest classifier trained with DE miRNAs achieved a high accuracy of 97% for severe uncontrolled patient stratification. Validation of the identified biomarkers was performed on a subset of allergic asthmatic patients from the CAMP cohort at Brigham and Women’s Hospital, Harvard Medical School. Four of these miRNAs (hsa-miR-99b-5p, hsa-miR-451a, hsa-miR-326 and hsa-miR-505-3p) were validated, pointing towards their potential as biomarkers for stratifying allergic asthmatic patients by severity and providing insights into severe uncontrolled asthma molecular pathways.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Porfetye2024,

title = {How Do Molecular Tweezers Bind to Proteins? Lessons from X-ray Crystallography},

author = {Arthur T. Porfetye and Patricia Stege and Rocio Rebollido-Rios and Daniel Hoffmann and Thomas Schrader and Ingrid R. Vetter},

doi = {10.3390/molecules29081764},

issn = {1420-3049},

year  = {2024},

date = {2024-04-00},

urldate = {2024-04-00},

journal = {Molecules},

volume = {29},

number = {8},

publisher = {MDPI AG},

abstract = {<jats:p>To understand the biological relevance and mode of action of artificial protein ligands, crystal structures with their protein targets are essential. Here, we describe and investigate all known crystal structures that contain a so-called “molecular tweezer” or one of its derivatives with an attached natural ligand on the respective target protein. The aromatic ring system of these compounds is able to include lysine and arginine side chains, supported by one or two phosphate groups that are attached to the half-moon-shaped molecule. Due to their marked preference for basic amino acids and the fully reversible binding mode, molecular tweezers are able to counteract pathologic protein aggregation and are currently being developed as disease-modifying therapies against neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. We analyzed the corresponding crystal structures with 14-3-3 proteins in complex with mono- and diphosphate tweezers. Furthermore, we solved crystal structures of two different tweezer variants in complex with the enzyme Δ1-Pyrroline-5-carboxyl-dehydrogenase (P5CDH) and found that the tweezers are bound to a lysine and methionine side chain, respectively. The different binding modes and their implications for affinity and specificity are discussed, as well as the general problems in crystallizing protein complexes with artificial ligands.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hassenrück2023b,

title = {Functional impact and molecular binding modes of drugs that target the PI3K isoform p110δ},

author = {Floyd Hassenrück and Maria Farina-Morillas and Lars Neumann and Francesco Landini and Stuart James Blakemore and Mina Rabipour and Juan Raul Alvarez-Idaboy and Christian P. Pallasch and Michael Hallek and Rocio Rebollido-Rios and Günter Krause},

doi = {10.1038/s42003-023-04921-z},

issn = {2399-3642},

year  = {2023},

date = {2023-12-00},

urldate = {2023-12-00},

journal = {Commun Biol},

volume = {6},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title><jats:p>Targeting the PI3K isoform p110δ against B cell malignancies is at the mainstay of PI3K inhibitor (PI3Ki) development. Therefore, we generated isogenic cell lines, which express wild type or mutant p110δ, for assessing the potency, isoform-selectivity and molecular interactions of various PI3Ki chemotypes. The affinity pocket mutation I777M maintains p110δ activity in the presence of idelalisib, as indicated by intracellular AKT phosphorylation, and rescues cell functions such as p110δ-dependent cell viability. Resistance owing to this substitution consistently affects the potency of p110δ-selective in contrast to most multi-targeted PI3Ki, thus distinguishing usually propeller-shaped and typically flat molecules. Accordingly, molecular dynamics simulations indicate that the I777M substitution disturbs conformational flexibility in the specificity or affinity pockets of p110δ that is necessary for binding idelalisib or ZSTK474, but not copanlisib. In summary, cell-based and molecular exploration provide comparative characterization of currently developed PI3Ki and structural insights for future PI3Ki design.</jats:p>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36899005,

title = {LYN kinase programs stromal fibroblasts to facilitate leukemic survival via regulation of c-JUN and THBS1},

author = {Alexander F Vom Stein and Rocio Rebollido-Rios and Anna Lukas and Maximilian Koch and Anton von Lom and Sebastian Reinartz and Daniel Bachurski and France Rose and Katarzyna Bozek and Ali T Abdallah and Viktoria Kohlhas and Julia Saggau and Rebekka Zölzer and Yue Zhao and Christiane Bruns and Paul J Bröckelmann and Philipp Lohneis and Reinhard Büttner and Björn Häupl and Thomas Oellerich and Phuong-Hien Nguyen and Michael Hallek},

doi = {10.1038/s41467-023-36824-2},

issn = {2041-1723},

year  = {2023},

date = {2023-03-01},

urldate = {2023-03-01},

journal = {Nature Communications},

volume = {14},

number = {1},

pages = {1330},

abstract = {Microenvironmental bystander cells are essential for the progression of chronic lymphocytic leukemia (CLL). We have discovered previously that LYN kinase promotes the formation of a microenvironmental niche for CLL. Here we provide mechanistic evidence that LYN regulates the polarization of stromal fibroblasts to support leukemic progression. LYN is overexpressed in fibroblasts of lymph nodes of CLL patients. LYN-deficient stromal cells reduce CLL growth in vivo. LYN-deficient fibroblasts show markedly reduced leukemia feeding capacity in vitro. Multi-omics profiling reveals that LYN regulates the polarization of fibroblasts towards an inflammatory cancer-associated phenotype through modulation of cytokine secretion and extracellular matrix composition. Mechanistically, LYN deletion reduces inflammatory signaling including reduction of c-JUN expression, which in turn augments the expression of Thrombospondin-1, which binds to CD47 thereby impairing CLL viability. Together, our findings suggest that LYN is essential for rewiring fibroblasts towards a leukemia-supportive phenotype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35344582,

title = {Extracellular vesicles and PD-L1 suppress macrophages, inducing therapy resistance in TP53-deficient B-cell malignancies},

author = {Elena Izquierdo and Daniela Vorholt and Stuart Blakemore and Benedict Sackey and Janica L Nolte and Verena Barbarino and Jan Schmitz and Nadine Nickel and Daniel Bachurski and Liudmila Lobastova and Milos Nikolic and Michael Michalik and Reinhild Brinker and Olaf Merkel and Marek Franitza and Theodoros Georgomanolis and René Neuhaus and Maximilian Koch and Niklas Nasada and Gero Knittel and Björn Chapuy and Nicole Ludwig and Eckart Meese and Lukas Frenzel and Hans Christian Reinhardt and Martin Peifer and Rocio Rebollido-Rios and Heiko Bruns and Marcus Krüger and Michael Hallek and Christian P Pallasch},

doi = {10.1182/blood.2021014007},

issn = {1528-0020},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Blood},

volume = {139},

number = {25},

pages = {3617--3629},

abstract = {Genetic alterations in the DNA damage response (DDR) pathway are a frequent mechanism of resistance to chemoimmunotherapy (CIT) in B-cell malignancies. We have previously shown that the synergy of CIT relies on secretory crosstalk elicited by chemotherapy between the tumor cells and macrophages. Here, we show that loss of multiple different members of the DDR pathway inhibits macrophage phagocytic capacity in vitro and in vivo. Particularly, loss of TP53 led to decreased phagocytic capacity ex vivo across multiple B-cell malignancies. We demonstrate via in vivo cyclophosphamide treatment using the Eμ-TCL1 mouse model that loss of macrophage phagocytic capacity in Tp53-deleted leukemia is driven by a significant downregulation of a phagocytic transcriptomic signature using small conditional RNA sequencing. By analyzing the tumor B-cell proteome, we identified a TP53-specific upregulation of proteins associated with extracellular vesicles (EVs). We abrogated EV biogenesis in tumor B-cells via clustered regularly interspaced short palindromic repeats (CRISPR)-knockout (KO) of RAB27A and confirmed that the EVs from TP53-deleted lymphoma cells were responsible for the reduced phagocytic capacity and the in vivo CIT resistance. Furthermore, we observed that TP53 loss led to an upregulation of both PD-L1 cell surface expression and secretion of EVs by lymphoma cells. Disruption of EV bound PD-L1 by anti-PD-L1 antibodies or PD-L1 CRISPR-KO improved macrophage phagocytic capacity and in vivo therapy response. Thus, we demonstrate enhanced EV release and increased PD-L1 expression in TP53-deficient B-cell lymphomas as novel mechanisms of macrophage function alteration in CIT resistance. This study indicates the use of checkpoint inhibition in the combination treatment of B-cell malignancies with TP53 loss.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36514317,

title = {HPIPred: Host-pathogen interactome prediction with phenotypic scoring},

author = {Javier Macho Rendón and Rocio Rebollido-Ríos and Marc Torrent Burgas},

doi = {10.1016/j.csbj.2022.11.026},

issn = {2001-0370},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Comput Struct Biotechnol J},

volume = {20},

pages = {6534--6542},

abstract = {Protein-protein interactions (PPIs) are involved in most cellular processes. Unfortunately, current knowledge of host-pathogen interactomes is still very limited. Experimental methods used to detect PPIs have several limitations, including increasing complexity and economic cost in large-scale screenings. Hence, computational methods are commonly used to support experimental data, although they generally suffer from high false-positive rates. To address this issue, we have created HPIPred, a host-pathogen PPI prediction tool based on numerical encoding of physicochemical properties. Unlike other available methods, HPIPred integrates phenotypic data to prioritize biologically meaningful results. We used HPIPred to screen the entire  and  PAO1 proteomes to generate a host-pathogen interactome with 763 interactions displaying a highly connected network topology. Our predictive model can be used to prioritize protein-protein interactions as potential targets for antibacterial drug development. Available at: https://github.com/SysBioUAB/hpi_predictor.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36714146,

title = {Stromal cells support the survival of human primary chronic lymphocytic leukemia (CLL) cells through Lyn-driven extracellular vesicles},

author = {Thaís Dolzany de Oliveira and Alexander Vom Stein and Rocio Rebollido-Rios and Liudmila Lobastova and Marcus Lettau and Ottmar Janssen and Prerana Wagle and Phuong-Hien Nguyen and Michael Hallek and Hinrich P Hansen},

doi = {10.3389/fmed.2022.1059028},

issn = {2296-858X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Med (Lausanne)},

volume = {9},

pages = {1059028},

abstract = {INTRODUCTION: In chronic lymphocytic leukemia (CLL), the tumor cells receive survival support from stromal cells through direct cell contact, soluble factors and extracellular vesicles (EVs). The protein tyrosine kinase Lyn is aberrantly expressed in the malignant and stromal cells in CLL tissue. We studied the role of Lyn in the EV-based communication and tumor support.



METHODS: We compared the Lyn-dependent EV release, uptake and functionality using Lyn-proficient (wild-type) and -deficient stromal cells and primary CLL cells.



RESULTS: Lyn-proficient cells caused a significantly higher EV release and EV uptake as compared to Lyn-deficient cells and also conferred stronger support of primary CLL cells. Proteomic comparison of the EVs from Lyn-proficient and -deficient stromal cells revealed 70 significantly differentially expressed proteins. Gene ontology studies categorized many of which to organization of the extracellular matrix, such as collagen, fibronectin, fibrillin, Lysyl oxidase like 2, integrins and endosialin (CD248). In terms of function, a knockdown of CD248 in Lyn HS-5 cells resulted in a diminished B-CLL cell feeding capacity compared to wildtype or scrambled control cells. CD248 is a marker of certain tumors and cancer-associated fibroblast (CAF) and crosslinks fibronectin and collagen in a membrane-associated context.



CONCLUSION: Our data provide preclinical evidence that the tyrosine kinase Lyn crucially influences the EV-based communication between stromal and primary B-CLL cells by raising EV release and altering the concentration of functional molecules of the extracellular matrix.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33010229,

title = {Polyphenols bind to low density lipoprotein at biologically relevant concentrations that are protective for heart disease},

author = {Wei-Cheng Tung and Bryan Rizzo and Yusef Dabbagh and Suraj Saraswat and Mark Romanczyk and Edelsys Codorniu-Hernández and Rocio Rebollido-Rios and Paul W Needs and Paul A Kroon and Njara Rakotomanomana and Olivier Dangles and Karen Weikel and Joe Vinson},

doi = {10.1016/j.abb.2020.108589},

issn = {1096-0384},

year  = {2020},

date = {2020-11-01},

urldate = {2020-11-01},

journal = {Arch Biochem Biophys},

volume = {694},

pages = {108589},

abstract = {There is ample evidence in the epidemiological literature that polyphenols, the major non-vitamin antioxidants in plant foods and beverages, have a beneficial effect on heart disease. Until recently other mechanisms which polyphenols exhibit such as cell signaling and regulating nitric oxide bioavailability have been investigated. The oxidation theory of atherosclerosis implicates LDL oxidation as the beginning step in this process. Nine polyphenols from eight different classes and several of their O-methylether, O-glucuronide and O-sulfate metabolites have been shown in this study to bind to the lipoproteins and protect them from oxidation at lysosomal/inflammatory pH (5.2), and physiological pH (7.4). Polyphenols bind to the apoprotein at pH 7.4 with K > 10 M and the number of molecules of polyphenols bound per LDL particle under saturation conditions varied from 0.4 for ferulic acid to 13.1 for quercetin. Competition studies between serum albumin and LDL show that substantial lipoprotein binding occurs even in the presence of a great molar excess of albumin, the major blood protein. These in vitro results are borne out by published human supplementation studies showing that polyphenol metabolites from red wine, olive oil and coffee are found in LDL even after an overnight fast. A single human supplementation with various fruit juices, coffee and tea also produced an ex vivo protection against lipoprotein oxidation under postprandial conditions. This in vivo binding is heart-protective based on published olive oil consumption studies. Relevant to heart disease, we hypothesize that the binding of polyphenols and metabolites to LDL functions as a transport mechanism to carry these antioxidants to the arterial intima, and into endothelial cells and macrophages. Extracellular and intracellular polyphenols and their metabolites are heart-protective by many mechanisms and can also function as potent "intraparticle" and intracellular antioxidants due to their localized concentrations that can reach as high as the micromolar level. Low plasma concentrations make polyphenols and their metabolites poor plasma antioxidants but their concentration in particles such as lipoproteins and cells is high enough for polyphenols to provide cardiovascular protection by direct antioxidant effects and by other mechanisms such as cell signaling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32015486,

title = {Dual disruption of aldehyde dehydrogenases 1 and 3 promotes functional changes in the glutathione redox system and enhances chemosensitivity in nonsmall cell lung cancer},

author = {Rocio Rebollido-Rios and Geoffroy Venton and Sara Sánchez-Redondo and Carmela Iglesias I Felip and Guy Fournet and Elena González and Wilber Romero Fernández and Dasiel Oscar Borroto Escuela and Barbara Di Stefano and Reinier Penarroche-Díaz and Guillaume Martin and Ismail Ceylan and Regis Costello and Mileidys Perez-Alea},

doi = {10.1038/s41388-020-1184-9},

issn = {1476-5594},

year  = {2020},

date = {2020-03-01},

urldate = {2020-03-01},

journal = {Oncogene},

volume = {39},

number = {13},

pages = {2756--2771},

abstract = {Aldehyde dehydrogenases (ALDHs) are multifunctional enzymes that oxidize diverse endogenous and exogenous aldehydes. We conducted a meta-analysis based on The Cancer Genome Atlas and Gene Expression Omnibus data and detected genetic alterations in ALDH1A1, ALDH1A3, or ALDH3A1, 86% of which were gene amplification or mRNA upregulation, in 31% of nonsmall cell lung cancers (NSCLCs). The expression of these isoenzymes impacted chemoresistance and shortened survival times in patients. We hypothesized that these enzymes provide an oxidative advantage for the persistence of NSCLC. To test this hypothesis, we used genetic and pharmacological approaches with DIMATE, an irreversible inhibitor of ALDH1/3. DIMATE showed cytotoxicity in 73% of NSCLC cell lines tested and demonstrated antitumor activity in orthotopic xenografts via hydroxynonenal-protein adduct accumulation, GSTO1-mediated depletion of glutathione and increased HO. Consistent with this result, ALDH1/3 disruption synergized with ROS-inducing agents or glutathione synthesis inhibitors to trigger cell death. In lung cancer xenografts with high to moderate cisplatin resistance, combination treatment with DIMATE promoted strong synergistic responses with tumor regression. These results indicate that NSCLCs with increased expression of ALDH1A1, ALDH1A3, or ALDH3A1 may be targeted by strategies involving inhibitors of these isoenzymes as monotherapy or in combination with chemotherapy to overcome patient-specific drug resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29187635,

title = {Structural similarities in the CPC clip motif explain peptide-binding promiscuity between glycosaminoglycans and lipopolysaccharides},

author = {David Pulido and Rocío Rebollido-Rios and Javier Valle and David Andreu and Ester Boix and Marc Torrent},

doi = {10.1098/rsif.2017.0423},

issn = {1742-5662},

year  = {2017},

date = {2017-11-01},

urldate = {2017-11-01},

journal = {J R Soc Interface},

volume = {14},

number = {136},

abstract = {Lipopolysaccharides (LPSs) and glycosaminoglycans (GAGs) are polymeric structures containing negatively charged disaccharide units that bind to specialized proteins and peptides in the human body and control fundamental processes such as inflammation and coagulation. Surprisingly, some proteins can bind both LPSs and GAGs with high affinity, suggesting that a cross-communication between these two pathways can occur. Here, we explore whether GAGs and LPSs can share common binding sites in proteins and what are the structural determinants of this binding. We found that the LPS-binding peptide YI12WF, derived from protein FhuA, can bind both heparin and  LPS with high affinity. Most interestingly, mutations decreasing heparin binding in the peptide also reduce LPS affinity. We show that such mutations involve the CPC clip motif in the peptide, a small three-dimensional signature required for heparin binding. Overall, we conclude that negatively charged polysaccharide-containing polymers such as GAGs and LPSs can compete for similar binding sites in proteins, and that the CPC clip motif is essential to bind both ligands. Our results provide a structural framework to explain why these polymers can cross-interact with the same proteins and peptides and thus contribute to the regulation of apparently unrelated processes in the body.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28778988,

title = {Ca coordination controls sonic hedgehog structure and its Scube2-regulated release},

author = {Petra Jakobs and Philipp Schulz and Sabine Schürmann and Stephan Niland and Sebastian Exner and Rocio Rebollido-Rios and Dominique Manikowski and Daniel Hoffmann and Daniela G Seidler and Kay Grobe},

doi = {10.1242/jcs.205872},

issn = {1477-9137},

year  = {2017},

date = {2017-10-01},

urldate = {2017-10-01},

journal = {J Cell Sci},

volume = {130},

number = {19},

pages = {3261--3271},

abstract = {Proteolytic processing of cell-surface-bound ligands, called shedding, is a fundamental system to control cell-cell signaling. Yet, our understanding of how shedding is regulated is still incomplete. One way to increase the processing of dual-lipidated membrane-associated Sonic hedgehog (Shh) is to increase the density of substrate and sheddase. This releases and also activates Shh by the removal of lipidated inhibitory N-terminal peptides from Shh receptor binding sites. Shh release and activation is enhanced by Scube2 [signal sequence, cubulin (CUB) domain, epidermal growth factor (EGF)-like protein 2], raising the question of how this is achieved. Here, we show that Scube2 EGF domains are responsible for specific proteolysis of the inhibitory Shh N-terminus, and that CUB domains complete the process by reversing steric masking of this peptide. Steric masking, in turn, depends on Ca occupancy of Shh ectodomains, unveiling a new mode of shedding regulation at the substrate level. Importantly, Scube2 uncouples processing of Shh peptides from their lipid-mediated juxtamembrane positioning, and thereby explains the long-standing conundrum that N-terminally unlipidated Shh shows patterning activity in Scube2-expressing vertebrates, but not in invertebrates that lack Scube orthologs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25033298,

title = {Signaling domain of Sonic Hedgehog as cannibalistic calcium-regulated zinc-peptidase},

author = {Rocio Rebollido-Rios and Shyam Bandari and Christoph Wilms and Stanislav Jakuschev and Andrea Vortkamp and Kay Grobe and Daniel Hoffmann},

doi = {10.1371/journal.pcbi.1003707},

issn = {1553-7358},

year  = {2014},

date = {2014-07-01},

urldate = {2014-07-01},

journal = {PLoS Comput Biol},

volume = {10},

number = {7},

pages = {e1003707},

abstract = {Sonic Hedgehog (Shh) is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN) is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog), of which all members harbor a structurally well-defined Zn2+ center; however, it is remarkable that ShhN so far is the only LAS member without proven peptidase activity. Another unique feature of ShhN in the LAS group is a double-Ca2+ center close to the zinc. We have studied the effect of these calcium ions on ShhN structure, dynamics, and interactions. We find that the presence of calcium has a marked impact on ShhN properties, with the two calcium ions having different effects. The more strongly bound calcium ion significantly stabilizes the overall structure. Surprisingly, the binding of the second calcium ion switches the putative catalytic center from a state similar to LAS enzymes to a state that probably is catalytically inactive. We describe in detail the mechanics of the switch, including the effect on substrate co-ordinating residues and on the putative catalytic water molecule. The properties of the putative substrate binding site suggest that ShhN could degrade other ShhN molecules, e.g. by cleavage at highly conserved glycines in ShhN. To test experimentally the stability of ShhN against autodegradation, we compare two ShhN mutants in vitro: (1) a ShhN mutant unable to bind calcium but with putative catalytic center intact, and thus, according to our hypothesis, a constitutively active peptidase, and (2) a mutant carrying additionally mutation E177A, i.e., with the putative catalytically active residue knocked out. The in vitro results are consistent with ShhN being a cannibalistic zinc-peptidase. These experiments also reveal that the peptidase activity depends on pH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}