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Article: Metabolic engineering of Bacillus subtilis toward the efficient and stable production of C

Filluelo, Oriana / Ferrando, Jordi / Picart, Pere

2023 Volume 13, Issue 1, Page(s) 38

Abstract: ... C ...

Abstract	Commercial carotenoid production is dominated by chemical synthesis and plant extraction, both of which are unsustainable and can be detrimental to the environment. A promising alternative for the mass production of carotenoids from both an ecological and commercial perspective is microbial synthesis. To date, C
Language	English
Publishing date	2023-04-29
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2621432-5
ISSN	2191-0855
ISSN	2191-0855
DOI	10.1186/s13568-023-01542-x
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Article ; Online: Gene expression profiling of epidermal cell types in C. elegans using Targeted DamID.

Katsanos, Dimitris / Ferrando-Marco, Mar / Razzaq, Iqrah / Aughey, Gabriel / Southall, Tony D / Barkoulas, Michalis

Development (Cambridge, England)

2021 Volume 148, Issue 17

Abstract: ... in C. elegans as a method for identifying genes expressed within a tissue of interest without cell ...

Abstract	The epidermis of Caenorhabditis elegans is an essential tissue for survival because it contributes to the formation of the cuticle barrier as well as facilitating developmental progression and animal growth. Most of the epidermis consists of the hyp7 hypodermal syncytium, the nuclei of which are largely generated by the seam cells, which exhibit stem cell-like behaviour during development. How seam cell progenitors differ transcriptionally from the differentiated hypodermis is poorly understood. Here, we introduce Targeted DamID (TaDa) in C. elegans as a method for identifying genes expressed within a tissue of interest without cell isolation. We show that TaDa signal enrichment profiles can be used to identify genes transcribed in the epidermis and use this method to resolve differences in gene expression between the seam cells and the hypodermis. Finally, we predict and functionally validate new transcription and chromatin factors acting in seam cell development. These findings provide insights into cell type-specific gene expression profiles likely associated with epidermal cell fate patterning.
MeSH term(s)	Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Cell Differentiation ; Cell Lineage ; Chromatin/genetics ; Chromatin/metabolism ; Epidermal Cells/cytology ; Epidermal Cells/metabolism ; Epidermis/growth & development ; Epidermis/metabolism ; Gene Expression Profiling/methods ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Caenorhabditis elegans Proteins ; Chromatin ; MicroRNAs ; Transcription Factors
Language	English
Publishing date	2021-09-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.199452
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Article ; Online: Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency.

Martos, Laura / Fernández-Pardo, Álvaro / López-Fernández, María F / Ibáñez, Francisco / Herrero, Sonia / Tàssies, Dolors / González-Porras, José R / Solmoirago, María J / Costa, María J / Reverter, Juan C / Marco, Pascual / Roldán, Vanessa / Lecumberri, Ramón / Velasco, Francisco / Oto, Julia / Iruin, Gemma / Alonso, María N / Vayá, Amparo / Bonanad, Santiago /

Ferrando, Fernando / Martí, Edelmira / Cid, Ana R / Plana, Emma / Oña, Francisca / Cuesta, Isabel / González-López, Tomás J / España, Francisco / Medina, Pilar / Navarro, Silvia

Thrombosis and haemostasis

2019 Volume 119, Issue 9, Page(s) 1409–1418

Abstract: Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is ...

Abstract	Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene (
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Coagulation/genetics ; Child ; Child, Preschool ; DNA Mutational Analysis ; France ; Humans ; Medical History Taking ; Middle Aged ; Mutation/genetics ; Netherlands ; Pedigree ; Protein C/genetics ; Protein C Deficiency/genetics ; Spain ; Venous Thromboembolism/genetics ; Young Adult
Chemical Substances	Protein C
Language	English
Publishing date	2019-06-29
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0039-1692440
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Article ; Online: Increase of Neutrophil Activation Markers in Venous Thrombosis-Contribution of Circulating Activated Protein C.

Martos, Laura / Oto, Julia / Fernández-Pardo, Álvaro / Plana, Emma / Solmoirago, María José / Cana, Fernando / Hervás, David / Bonanad, Santiago / Ferrando, Fernando / España, Francisco / Navarro, Silvia / Medina, Pilar

International journal of molecular sciences

2020 Volume 21, Issue 16

Abstract: ... and NETosis, thus prompting thrombosis. The natural anticoagulant activated protein C (APC) inhibits ... In them, we also quantified plasma APC, soluble endothelial protein C receptor (EPCR), and soluble thrombomodulin ...

Abstract	Upon activation, neutrophils release their content through different mechanisms like degranulation and NETosis, thus prompting thrombosis. The natural anticoagulant activated protein C (APC) inhibits neutrophil NETosis and, consequently, this may lower the levels of neutrophil activation markers in plasma, further diminishing the thrombotic risk exerted by this anticoagulant. We aimed to describe the status of markers of neutrophil activation in plasma of patients with venous thrombosis, their association with the thrombotic risk and the potential contribution of APC. We quantified three markers of neutrophil activation (cell-free DNA, calprotectin, and myeloperoxidase) in 253 patients with venous thromboembolism (VTE) in a stable phase (192 lower extremity VTE and 61 splanchnic vein thrombosis) and in 249 healthy controls. In them, we also quantified plasma APC, soluble endothelial protein C receptor (EPCR), and soluble thrombomodulin (TM), and we genotyped two genetic regulators of APC: the EPCR gene (
MeSH term(s)	Adult ; Biomarkers/blood ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Neutrophil Activation ; Protein C/genetics ; Protein C/metabolism ; Risk Factors ; Venous Thrombosis/blood ; Venous Thrombosis/pathology
Chemical Substances	Biomarkers ; Protein C
Language	English
Publishing date	2020-08-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21165651
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Article ; Online: Hepatitis C virus replication in Caucasian HIV controllers.

Ruiz-Mateos, E / Machmach, K / Romero-Sanchez, M C / Ferrando-Martinez, S / Viciana, P / Del Val, M / Muñoz-Fernandez, M A / Genebat, M / Leal, M

Journal of viral hepatitis

2011 Volume 18, Issue 7, Page(s) e350–7

Abstract: ... hepatitis C virus (HCV) infection, in terms of spontaneous clearance or lower HCV replication, is not well ...

Abstract	Whether HIV controllers, patients who spontaneously control HIV viraemia, are able to control hepatitis C virus (HCV) infection, in terms of spontaneous clearance or lower HCV replication, is not well understood. To assess to what extent Caucasian HIV controllers are able to control HCV replication and potential associated factors, plasma HIV-1 and HCV RNA levels, anti-HCV antibodies, HCV genotype and human leucocyte antigens (HLA) typing were determined in samples from 75 HIV controllers (33 viraemic controllers, <1000 HIV-1 RNA copies/mL, and 42 elite controllers, <40 HIV-1 RNA copies/mL) and compared with 261 HIV-infected noncontrollers. We did not find differences in the HCV spontaneous clearance rates between groups. However, we interestingly found a lower HCV viral load in HIV controllers, alongside a different distribution of HCV genotypes in relation to the comparison group. In addition, HLA-B57 was associated with a lower HCV viral load in the control group and HIV controllers, and conversely, HLA-B35 with higher HCV viral load in HIV controllers. The subrepresentation of HCV genotype 1 and the overrepresentation of HLA-B57 only partly explained the lower HCV viral load found in HIV controllers. In fact, HIV controller status was independently associated with lower HCV viral load, together with HCV genotype non-1, the presence of HLA-B57 and absence of HLA-B35. Caucasian HIV controllers are able to better control HCV replication, in terms of lower HCV viral load levels. These findings support the idea that some common host mechanisms are involved in the defence against these two persistent infections.
MeSH term(s)	Adult ; Coinfection/virology ; European Continental Ancestry Group ; Female ; HIV Infections/complications ; HIV Infections/immunology ; HIV Infections/virology ; HLA-B Antigens/immunology ; HLA-B35 Antigen/immunology ; Hepacivirus/physiology ; Hepatitis C/complications ; Hepatitis C/immunology ; Hepatitis C/virology ; Humans ; Immunity, Innate ; Male ; Middle Aged ; RNA, Viral/biosynthesis ; RNA, Viral/blood ; RNA, Viral/immunology ; Viral Load ; Viremia/immunology ; Viremia/virology ; Virus Replication
Chemical Substances	HLA-B Antigens ; HLA-B35 Antigen ; HLA-B57 antigen ; RNA, Viral
Language	English
Publishing date	2011-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/j.1365-2893.2010.01431.x
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Article ; Online: Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release.

Suofu, Yalikun / Li, Wei / Jean-Alphonse, Frédéric G / Jia, Jiaoying / Khattar, Nicolas K / Li, Jiatong / Baranov, Sergei V / Leronni, Daniela / Mihalik, Amanda C / He, Yanqing / Cecon, Erika / Wehbi, Vanessa L / Kim, JinHo / Heath, Brianna E / Baranova, Oxana V / Wang, Xiaomin / Gable, Matthew J / Kretz, Eric S / Di Benedetto, Giulietta /

Lezon, Timothy R / Ferrando, Lisa M / Larkin, Timothy M / Sullivan, Mara / Yablonska, Svitlana / Wang, Jingjing / Minnigh, M Beth / Guillaumet, Gérald / Suzenet, Franck / Richardson, R Mark / Poloyac, Samuel M / Stolz, Donna B / Jockers, Ralf / Witt-Enderby, Paula A / Carlisle, Diane L / Vilardaga, Jean-Pierre / Friedlander, Robert M

Proceedings of the National Academy of Sciences of the United States of America

2017 Volume 114, Issue 38, Page(s) E7997–E8006

Abstract: G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor ( ... ...

Abstract	G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT
MeSH term(s)	Animals ; Brain Injuries/genetics ; Brain Injuries/metabolism ; Brain Ischemia/genetics ; Brain Ischemia/metabolism ; Cytochromes c/genetics ; Cytochromes c/metabolism ; Male ; Melatonin/biosynthesis ; Melatonin/genetics ; Mice ; Mitochondria/genetics ; Mitochondria/metabolism ; Receptor, Melatonin, MT1/genetics ; Receptor, Melatonin, MT1/metabolism ; Signal Transduction
Chemical Substances	Receptor, Melatonin, MT1 ; Cytochromes c (9007-43-6) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2017-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1705768114
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Article: Identification of 58 Mutations (26 Novel) in 94 of 109 Symptomatic Spanish Probands with Protein C Deficiency

Martos, Laura / Fernández-Pardo, Álvaro / López-Fernández, María F. / Ibáñez, Francisco / Herrero, Sonia / Tàssies, Dolors / González-Porras, José R. / Solmoirago, María J. / Costa, María J. / Reverter, Juan C. / Marco, Pascual / Roldán, Vanessa / Lecumberri, Ramón / Velasco, Francisco / Oto, Julia / Iruin, Gemma / Alonso, María N. / Vayá, Amparo / Bonanad, Santiago /

Ferrando, Fernando / Martí, Edelmira / Cid, Ana R. / Plana, Emma / Oña, Francisca / Cuesta, Isabel / González-López, Tomás J. / España, Francisco / Medina, Pilar / Navarro, Silvia

Thrombosis and Haemostasis

2019 Volume 119, Issue 09, Page(s) 1409–1418

Abstract: Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is ...

Abstract	Presently, no data on the molecular basis of hereditary protein C (PC) deficiency in Spain is available. We analyzed the PC gene ( PROC ) in 109 patients with symptomatic PC deficiency and in 342 relatives by sequencing the 9 PROC exons and their flanking intron regions. In 93 probands, we found 58 different mutations (26 novel). Thirty-seven consisted of a nucleotide change, mainly missense mutations, 1 was a 6-nucleotide insertion causing the duplication of 2 amino acids, and 4 were deletions of 1, 3, 4, and 16 nucleotides. Nine mutations caused type II deficiencies, with the presence of normal antigen levels but reduced anticoagulant activity. Using a PC level of 70% as lowest normal limit, we found no mutations in 16 probands and 25 relatives with PC levels ≤ 70%. On the contrary, 4 probands and 12 relatives with PC levels > 70% carried the mutation identified in the proband. The spectrum of recurrent mutations in Spain is different from that found in the Netherlands, where the most frequent mutations were p.Gln174* and p.Arg272Cys, and is more similar to that found in France, where the most frequent were p.Arg220Gln and p.Pro210Leu. In our study, p.Val339Met (9 families), p.Tyr166Cys (7), p.Arg220Gln (6), and p.Glu58Lys (5) were the most prevalent. This study confirms the considerable heterogeneity of the genetic abnormality in PC deficiencies, and allowed genetic counseling to those individuals whose PC levels were close to the lower limit of the normal reference range.
Keywords	protein C deficiency ; gene mutations ; venous thromboembolism ; family study
Language	English
Publishing date	2019-06-29
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0039-1692440
Database	Thieme publisher's database

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Article: Managing Hepatitis C in Users of Illicit Drugs.

Edlin, Brian R / Carden, Michael R / Ferrando, Stephen J

Current hepatitis reports

2013 Volume 6, Issue 2, Page(s) 60–67

Abstract: Persons who inject illicit drugs are the group most severely affected by the hepatitis C epidemic ... of drug users treated for hepatitis C can achieve sustained virologic responses even if they have psychiatric ... comorbidity and even if they continue to use drugs while receiving hepatitis C treatment. Successfully ...

Abstract	Persons who inject illicit drugs are the group most severely affected by the hepatitis C epidemic but the least likely to receive treatment. Controlling the epidemic will require developing strategies for effectively treating drug users. A growing number of reports have shown that a substantial proportion of drug users treated for hepatitis C can achieve sustained virologic responses even if they have psychiatric comorbidity and even if they continue to use drugs while receiving hepatitis C treatment. Successfully treating hepatitis C in injection drug users requires collaboration between those with expertise in hepatitis and those with expertise in caring for substance users. Careful attention to management of adverse effects and strong links with mental health services are important. Further research is needed to better define which patients can be successfully treated and the program elements that are critical for success. In the meantime, substantial progress can be made using current knowledge if appropriate resources are brought to bear.
Language	English
Publishing date	2013-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2186590-5
ISSN	1541-0706 ; 1540-3416
ISSN (online)	1541-0706
ISSN	1540-3416
DOI	10.1007/s11901-007-0005-8
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Article ; Online: POLYMAT-C: a comprehensive SPSS program for computing the polychoric correlation matrix.

Lorenzo-Seva, Urbano / Ferrando, Pere J

Behavior research methods

2015 Volume 47, Issue 3, Page(s) 884–889

Abstract: ... for each element of the matrix by using appropriate simulation procedures; (c) obtaining valid and accurate ...

Abstract	We provide a free noncommercial SPSS program that implements procedures for (a) obtaining the polychoric correlation matrix between a set of ordered categorical measures, so that it can be used as input for the SPSS factor analysis (FA) program; (b) testing the null hypothesis of zero population correlation for each element of the matrix by using appropriate simulation procedures; (c) obtaining valid and accurate confidence intervals via bootstrap resampling for those correlations found to be significant; and (d) performing, if necessary, a smoothing procedure that makes the matrix amenable to any FA estimation procedure. For the main purpose (a), the program uses a robust unified procedure that allows four different types of estimates to be obtained at the user's choice. Overall, we hope the program will be a very useful tool for the applied researcher, not only because it provides an appropriate input matrix for FA, but also because it allows the researcher to carefully check the appropriateness of the matrix for this purpose. The SPSS syntax, a short manual, and data files related to this article are available as Supplemental materials that are available for download with this article.
MeSH term(s)	Factor Analysis, Statistical ; Humans ; Software ; Statistics as Topic/methods
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	231560-9
ISSN	1554-3528 ; 0743-3808 ; 1554-351X
ISSN (online)	1554-3528
ISSN	0743-3808 ; 1554-351X
DOI	10.3758/s13428-014-0511-x
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Article ; Online: Identification of targets of c-Src tyrosine kinase by chemical complementation and phosphoproteomics.

Ferrando, Isabel Martinez / Chaerkady, Raghothama / Zhong, Jun / Molina, Henrik / Jacob, Harrys K C / Herbst-Robinson, Katie / Dancy, Beverley M / Katju, Vikram / Bose, Ron / Zhang, Jin / Pandey, Akhilesh / Cole, Philip A

Molecular & cellular proteomics : MCP

2012 Volume 11, Issue 8, Page(s) 355–369

Abstract: The cellular proto-oncogene c-Src is a nonreceptor tyrosine kinase involved in cell growth and ... not fully understood. Identification of the substrates of c-Src remains a major challenge ... c-Src and global quantitative phosphoproteomics to obtain the first high resolution ...

Abstract	The cellular proto-oncogene c-Src is a nonreceptor tyrosine kinase involved in cell growth and cytoskeletal regulation. Despite being dysregulated in a variety of human cancers, its precise functions are not fully understood. Identification of the substrates of c-Src remains a major challenge, because there is no simple way to directly stimulate its activity. Here we combine the chemical rescue of mutant c-Src and global quantitative phosphoproteomics to obtain the first high resolution snapshot of the range of tyrosine phosphorylation events that occur in the cell immediately after specific c-Src stimulation. After enrichment by anti-phosphotyrosine antibodies, we identified 29 potential novel c-Src substrate proteins. Tyrosine phosphopeptide mapping allowed the identification of 382 nonredundant tyrosine phosphopeptides on 213 phosphoproteins. Stable isotope labeling of amino acids in cell culture-based quantitation allowed the detection of 97 nonredundant tyrosine phosphopeptides whose level of phosphorylation is increased by c-Src. A large number of previously uncharacterized c-Src putative protein targets and phosphorylation sites are presented here, a majority of which play key roles in signaling and cytoskeletal networks, particularly in cell adhesion. Integrin signaling and focal adhesion kinase signaling pathway are two of the most altered pathways upon c-Src activation through chemical rescue. In this context, our study revealed the temporal connection between c-Src activation and the GTPase Rap1, known to stimulate integrin-dependent adhesion. Chemical rescue of c-Src provided a tool to dissect the spatiotemporal mechanism of activation of the Rap1 guanine exchange factor, C3G, one of the identified potential c-Src substrates that plays a role in focal adhesion signaling. In addition to unveiling the role of c-Src in the cell and, specifically, in the Crk-C3G-Rap1 pathway, these results exemplify a strategy for obtaining a comprehensive understanding of the functions of nonreceptor tyrosine kinases with high specificity and kinetic resolution.
MeSH term(s)	Animals ; Blotting, Western ; CSK Tyrosine-Protein Kinase ; Embryo, Mammalian/cytology ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Focal Adhesions ; Guanine Nucleotide-Releasing Factor 2/metabolism ; Humans ; Imidazoles/chemistry ; Mass Spectrometry ; Mice ; Mice, Knockout ; Microscopy, Confocal ; Mutation ; Phosphopeptides/analysis ; Phosphoproteins/analysis ; Phosphorylation ; Protein Binding ; Proteomics/methods ; Signal Transduction ; Substrate Specificity ; Tyrosine/chemistry ; Tyrosine/genetics ; Tyrosine/metabolism ; rap1 GTP-Binding Proteins/metabolism ; src-Family Kinases/chemistry ; src-Family Kinases/genetics ; src-Family Kinases/metabolism
Chemical Substances	Guanine Nucleotide-Releasing Factor 2 ; Imidazoles ; Phosphopeptides ; Phosphoproteins ; Tyrosine (42HK56048U) ; CSK Tyrosine-Protein Kinase (EC 2.7.10.2) ; src-Family Kinases (EC 2.7.10.2) ; CSK protein, human (EC 2.7.10.23) ; rap1 GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2012-04-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2075924-1
ISSN	1535-9484 ; 1535-9476
ISSN (online)	1535-9484
ISSN	1535-9476
DOI	10.1074/mcp.M111.015750
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