Juan Carlos González‐Sánchez

Heidelberg University

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Alberto Muñoz-Prieto

Universidad de Murcia

Ivana Rubić

University of Zagreb

Vladimir Mrljak

University of Zagreb

Robert B. Russell

Heidelberg University

J. M. Castro Cerón

Universidad de Murcia

Asta Tvarijonaviciute

Universidad de Murcia

Silvia Martínez‐Subiela

Universidad de Murcia

Damien P. Devos

Centro Andaluz de Biología del Desarrollo

Josipa Kuleš

University of Zagreb

Gurdeep Singh

University of Manchester

Cooperative Institutions

Heidelberg University

Universidad de Murcia

German Cancer Research Center

Heidelberg University

European Molecular Biology Laboratory

University Hospital Heidelberg

Universidad Católica de Oriente

DKFZ-ZMBH Alliance

Deutschen Konsortium für Translationale Krebsforschung

European Molecular Biology Organization

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Changes in Serum Proteins in Cats with Obesity: A Proteomic Approach

Animals (2025)

Esmeralda Cañadas-Vidal Alberto Muñoz-Prieto Dina Rešetar Maslov Ivana Rubić Juan Carlos González‐Sánchez

Obesity is defined as the excessive accumulation of adipose tissue and is currently the most common disease in cats. Similarly to humans, obesity negatively impacts the health and welfare of cats, predisposing them to many other disorders. The objective of this study was to compare the serum proteomes of normal-weight and overweight/obese cats, aiming to gain insights into the physiopathology of feline obesity and potentially identify new biomarkers. For this, serum samples from a total of 20 adult neutered domestic shorthair client-owned cats, ten normal weight and ten overweight/obese, were submitted to tandem mass tags labelling and liquid chromatography-mass spectrometry (LC-MS/MS) analysis. A total of 288 proteins were detected in the serum samples. Out of these, 12 proteins showed statistically significant differences in abundance between control cats and cats with obesity, namely Ig-like domain-containing protein, Alpha-2-HS-glycoprotein, Complement C8 gamma chain, An-tithrombin-III, Serpin family A member 1, Complement factor H, C3-beta-c, Albumin, C4b-binding protein alpha chain, Alpha-1-B glycoprotein, Solute carrier family 12 member 4, and Fibronectin. Overall this report identifies new proteins involved and provides additional knowledge about the physiopathological changes related to feline obesity.

Tandem mass tag

Proteome

10.3390/ani15010091

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Citations (0)

Escuela, Educación Ambiental Y Contaminación Por Mercurio En Los Procesos De Minería Artesanal

Héctor Alonso García-Arango Juan Carlos González‐Sánchez

The present educational research article dealt with the recognition of the previous knowledge of students, and parents, of the Institucion Educativa Rural San Miguel regarding the effects of the use of Mercury in artisanal mining in the biotic and abiotic mass. The research corresponded to the first phase, exploratory with descriptive scope, of the integrative research oriented from the subject Natural Sciences and Environmental Education. In order to achieve the purpose of the investigation, the School Environmental Project was studied, and the perceptions of grade 5 students and their parents were recognized through a didactic sequence with the use of active pedagogies. The findings indicate the importance of constructing the School Environmental Project together with the community and of orienting the subject of Natural Sciences and Environmental Education from the reality of the territory in such a way that the pedagogical mediation provides elements of recognition of this, offers elements of reflection about care of the environment, conservation of biotic and abiotic factors while ensuring the sustainability and sustainability of the educational community and its environment.

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Cancer genetics meets biomolecular mechanism—bridging an age‐old gulf

FEBS Letters (2018)

Juan Carlos González‐Sánchez Francesco Raimondi Robert B. Russell

Increasingly available genomic sequencing data are exploited to identify genes and variants contributing to diseases, particularly cancer. Traditionally, methods to find such variants have relied heavily on allele frequency and/or familial history, often neglecting to consider any mechanistic understanding of their functional consequences. Thus, while the set of known cancer‐related genes has increased, for many, their mechanistic role in the disease is not completely understood. This issue highlights a wide gap between the disciplines of genetics, which largely aims to correlate genetic events with phenotype, and molecular biology, which ultimately aims at a mechanistic understanding of biological processes. Fortunately, new methods and several systematic studies have proved illuminating for many disease genes and variants by integrating sequencing with mechanistic data, including biomolecular structures and interactions. These have provided new interpretations for known mutations and suggested new disease‐relevant variants and genes. Here, we review these approaches and discuss particular examples where these have had a profound impact on the understanding of human cancers.

Human genetics

10.1002/1873-3468.12988

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Citations (9)

Rare, functional, somatic variants in gene families linked to cancer genes: GPCR signaling as a paradigm

Oncogene (2019)

Francesco Raimondi Asuka Inoue Francois Marie Ngako Kadji Shuai Ni Juan Carlos González‐Sánchez

Oncodriver genes are usually identified when mutations recur in multiple tumours. Different drivers often converge in the activation or repression of key cancer-relevant pathways. However, as many pathways contain multiple members of the same gene family, individual mutations might be overlooked, as each family member would necessarily have a lower mutation frequency and thus not identified as significant in any one-gene-at-a-time analysis. Here, we looked for mutated, functional sequence positions in gene families that were mutually exclusive (in patients) with another gene in the same pathway, which identified both known and new candidate oncodrivers. For instance, many inactivating mutations in multiple G-protein (particularly Gi/o) coupled receptors, are mutually exclusive with Gαs oncogenic activating mutations, both of which ultimately enhance cAMP signalling. By integrating transcriptomics and interaction data, we show that the Gs pathway is upregulated in multiple cancer types, even those lacking known GNAS activating mutations. This suggests that cancer cells may develop alternative strategies to activate adenylate cyclase signalling in multiple cancer types. Our study provides a mechanistic interpretation for several rare somatic mutations in multi-gene oncodrivers, and offers possible explanations for known and potential off-label cancer treatments, suggesting new therapeutic opportunities.

GNAS complex locus

10.1038/s41388-019-0895-2

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Citations (30)

PVCbase: an integrated web resource for the PVC bacterial proteomes

Database (2018)

Nicola Bordin Juan Carlos González‐Sánchez Damien P. Devos

Interest in the Planctomycetes-Verrucomicrobia-Chlamydiae (PVC) bacterial superphylum is growing within the microbiology community. These organisms do not have a specialized web resource that gathers in silico predictions in an integrated fashion. Hence, we are providing the PVC community with PVCbase, a specialized web resource that gathers in silico predictions in an integrated fashion. PVCbase integrates protein function annotations obtained through sequence analysis and tertiary structure prediction for 39 representative PVC proteomes (PVCdb), a protein feature visualizer (Foundation) and a custom BLAST webserver (PVCBlast) that allows to retrieve the annotation of a hit directly from the DataTables. We display results from various predictors, encompassing most functional aspects, allowing users to have a more comprehensive overview of protein identities. Additionally, we illustrate how the application of PVCdb can be used to address biological questions from raw data. Database URL: PVCbase is freely accessible at www.pvcbacteria.org/pvcbase

Web resource

Verrucomicrobia

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Web browser

10.1093/database/bay042

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Citations (14)

Changes of the salivary and serum proteome in canine hypothyroidism

Domestic Animal Endocrinology (2023)

Luis Guillermo González-Aróstegui Alberto Muñoz-Prieto Camila Peres Rubio J. M. Castro Cerón Luis J. Bernal

In this study, changes in salivary and serum proteome of dogs with hypothyroidism were studied using tandem mass tags (TMT) labelling and liquid chromatography-mass spectrometry (LC-MS/MS). Saliva and serum proteome from 10 dogs with hypothyroidism were compared with 10 healthy dogs. In saliva, a total of seven proteins showed significant changes between the two groups, being six downregulated and one upregulated, meanwhile, in serum, a total of six proteins showed significant changes, being five downregulated and one upregulated. The altered proteins reflected metabolic and immunologic changes, as well as, skin and coagulation alterations, and these proteins were not affected by gender. One of the proteins that were downregulated in saliva, lactate dehydrognease (LDH), was measured by a spectrophotometric assay in saliva samples from 42 dogs with hypothyroidism, 42 dogs with non-thyroid diseases and 46 healthy dogs. The activity of LDH was lower in the saliva of hypothyroid dogs when compared to non-thyroid diseased dogs and healthy controls. This study indicates that canine hypothyroidism can produce changes in the proteome of saliva and serum. These two sample types showed different variations in their proteins reflecting physiopathological changes that occur in this disease, mainly related to the immune system, metabolism, skin and coagulation. In addition, some of the proteins identified in this study, specially LDH in saliva, should be further explored as potential biomarkers of canine hypothyroidism.

Proteome

10.1016/j.domaniend.2023.106825

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Citations (2)

The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation

Nature Communications (2014)

Hideki Yokoyama Birgit Koch Rudolf Walczak Fulya Ciray-Duygu Juan Carlos González‐Sánchez

Ran

Microtubule nucleation

Spindle pole body

Nucleoporin

10.1038/ncomms4270

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Citations (60)

Focal structural variants revealed by whole genome sequencing disrupt the histone demethylase KDM4C in B-cell lymphomas

Haematologica (2022)

Cristina López Nikolai Schleußner Stephan Wolf Kortine Kleinheinz Stéphanie Sungalee

Histone methylation-modifiers, such as EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole genome and transcriptome data of 186 mature B-cell lymphomas sequenced in the ICGC MMML-Seq project. Besides confirming common alterations of KMT2D (47% of cases), EZH2 (17%), SETD1B (5%), PRDM9 (4%), KMT2C (4%), and SETD2 (4%), also identified by prior exome or RNA-sequencing studies, we here found recurrent alterations to KDM4C in chromosome 9p24, encoding a histone demethylase. Focal structural variation was the main mechanism of KDM4C alterations, and was independent from 9p24 amplification. We also identified KDM4C alterations in lymphoma cell lines including a focal homozygous deletion in a classical Hodgkin lymphoma cell line. By integrating RNA-sequencing and genome sequencing data we predict that KDM4C structural variants result in loss-offunction. By functional reconstitution studies in cell lines, we provide evidence that KDM4C can act as a tumor suppressor. Thus, we show that identification of structural variants in whole genome sequencing data adds to the comprehensive description of the mutational landscape of lymphomas and, moreover, establish KDM4C as a putative tumor suppressive gene recurrently altered in subsets of B-cell derived lymphomas.

Demethylase

Histone Methylation

10.3324/haematol.2021.280005

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A Proteomic Approach to Elucidate the Changes in Saliva and Serum Proteins of Pigs with Septic and Non-Septic Inflammation

International Journal of Molecular Sciences (2022)

María José López-Martínez J. M. Castro Cerón Alba Ortín-Bustillo Damián Escribano Josipa Kuleš

Sepsis is a systemic inflammatory response triggered by an infectious agent and is recognized by the World Health Organization as a global concern, since it is one of the major causes of severe illness in humans and animals. The study of the changes that can occur in saliva and serum in sepsis can contribute to a better understanding of the pathophysiological mechanisms involved in the process and also to discover potential biomarkers that can help in its diagnosis and monitoring. The objective of this study was to characterize the changes that occur in the salivary and serum proteome of pigs with experimentally-induced sepsis. The study included five pigs with sepsis induced by LPS administration and five pigs with non-septic inflammation induced by turpentine for comparative purposes. In saliva, there were eighteen salivary proteins differentially expressed in the sepsis condition and nine in non-septic inflammation. Among these, significant increments in aldolase A and serpin B12 only occurred in the sepsis model. Changes in aldolase A were validated in a larger population of pigs with sepsis due to Streptococcus suis infection. In serum, there were 30 proteins differentially expressed in sepsis group and 26 proteins in the non-septic group, and most of the proteins that changed in both groups were related to non-specific inflammation. In the saliva of the septic animals there were some specific pathways activated, such as the organonitrogen compound metabolic process and lipid transport, whereas, in the serum, one of the main activated pathways was the regulation of protein secretion. Overall, saliva and serum showed different proteome variations in response to septic inflammation and could provide complementary information about the pathophysiological mechanisms occurring in this condition. Additionally, salivary aldolase A could be a potential biomarker of sepsis in pigs that should be confirmed in a larger population.

Proteome

10.3390/ijms23126738

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Citations (17)

A Multi-Functional Tubulovesicular Network as the Ancestral Eukaryotic Endomembrane System

Biology (2015)

Juan Carlos González‐Sánchez Ricardo Almeida da Costa Damien P. Devos

The origin of the eukaryotic endomembrane system is still the subject of much speculation. We argue that the combination of two recent hypotheses addressing the eukaryotic endomembrane’s early evolution supports the possibility that the ancestral membranes were organised as a multi-functional tubulovesicular network. One of the potential selective advantages provided by this organisation was the capacity to perform endocytosis. This possibility is illustrated by membrane organisations observed in current organisms in the three domains of life. Based on this, we propose a coherent model of autogenous eukaryotic endomembrane system evolution in which mitochondria are involved at a late stage.

Endomembrane system

10.3390/biology4020264

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Citations (3)