Publications by authors named "Francisco Portillo"

Inulosucrases are enzymes capable of synthesizing inulin polymers using sucrose as the main substrate. The enzymatic activity relies on the catalytic triad within the active site and residues responsible for substrate recognition and orientation, termed carbohydrate-binding subsites. This study investigates the role of specific residues within the catalytic cavity of a truncated version of IslA4 in enzymatic catalysis.

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Unlabelled: Accessible Summary What is known on the subject? Functioning is one of the most affected areas in schizophrenia. Social, occupational and personal domains are affected, and these deficits are responsible for a major part of the disability associated with the disorder. There are several instruments to measure functioning, but the HoNOS provides a wide assessment of impairment in 12 areas of functioning.

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RNA-binding proteins play diverse roles in cancer, influencing various facets of the disease, including proliferation, apoptosis, angiogenesis, senescence, invasion, epithelial-mesenchymal transition (EMT), and metastasis. HuR, a known RBP, is recognized for stabilizing mRNAs containing AU-rich elements (AREs), although its complete repertoire of mRNA targets remains undefined. Through a bioinformatics analysis of the gene expression profile of the Hs578T basal-like triple-negative breast cancer cell line with silenced HuR, we have identified SOX9 as a potential HuR-regulated target.

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Lysyl Oxidase Like 2 (LOXL2) belongs to the lysyl oxidase (LOX) family, which comprises five lysine tyrosylquinone (LTQ)-dependent copper amine oxidases in humans. In 2003, LOXL2 was first identified as a promoter of tumour progression and, over the course of two decades, numerous studies have firmly established its involvement in multiple cancers. Extensive research with large cohorts of human tumour samples has demonstrated that dysregulated LOXL2 expression is strongly associated with poor prognosis in patients.

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Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer.

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Background: The brain functional correlates of delusions have been relatively little studied. However, a virtual reality paradigm simulating travel on the London Underground has been found to evoke referential ideation in both healthy subjects and patients with schizophrenia, making brain activations in response to such experiences potentially identifiable.

Method: Ninety patients with schizophrenia/schizoaffective disorder and 28 healthy controls underwent functional magnetic resonance imaging while they viewed virtual reality versions of full and empty Barcelona Metro carriages.

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Lysyl oxidase-like 2 (LOXL2) and 3 (LOXL3) are members of the lysyl oxidase family of enzymes involved in the maturation of the extracellular matrix. Both enzymes share a highly conserved catalytic domain, but it is unclear whether they perform redundant functions in vivo. In this study, we show that mice lacking Loxl3 exhibit perinatal lethality and abnormal skeletal development.

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Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous perception of speech. Anomalies of processing external speech stimuli have also been reported in people with AVH, but it is unexplored which specific dimensions of language are processed differently. Using a speech perception task (passive listening), we here targeted the processing of deixis, a key dimension of language governing the contextual anchoring of speech in interpersonal context.

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The stability of the power grid's frequency is crucial for industrial, commercial, and domestic applications. The standard frequency in Europe's grid is 50 Hz and it must be as stable as possible; therefore, reliable measurement is essential to ensure that the frequency is within the limits defined in the standard EN 50160:2010. In this article, a method has been introduced for the measurement of the grid frequency through a power line harmonics radiation analysis.

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Objective: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.

Design: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, ; ; mice (KPC) and the ; mice (KC) were crossed with allele floxed mice ( ) or conditional overexpressing mice (R26 ) to generate KPCL2 or KCL2 and KPCL2 or KCL2 mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.

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Malignant melanoma is a highly aggressive tumor causing most skin cancer-related deaths. Understanding the fundamental mechanisms responsible for melanoma progression and therapeutic evasion is still an unmet need for melanoma patients. Progression of skin melanoma and its dissemination to local or distant organs relies on phenotypic plasticity of melanoma cells, orchestrated by EMT-TFs and microphthalmia-associated TF (MITF).

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Deficits in emotion processing are a core feature of schizophrenia, but their neurobiological bases are poorly understood. Previous research, mainly focused on emotional face processing and emotion recognition deficits, has shown controverted results. Furthermore, the use of faces has been questioned for not entailing an appropriate stimulus to study emotional processing.

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An altered sense of self-awareness and agency has been proposed to underlie symptoms of schizophrenia. In this study, we used the enfacement illusion paradigm - in which perception of another person's face leads to changes in perception of one's own peri-personal space - to examine the brain correlates of the sense of agency and its potential disruption in schizophrenia. Thirty-three schizophrenic patients and 27 healthy controls underwent fMRI scanning during performance of a task designed to elicit the enfacement illusion.

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Article Synopsis
  • Cancer stem cells (CSC) play a critical role in tumor initiation, resistance to therapy, and metastasis, making understanding their mechanisms vital for new cancer treatments.
  • Research using a specialized mouse model shows that E2A transcription factors are essential for maintaining cancer stemness and enabling metastasis in breast cancer, as their deletion severely reduced tumor-initiating ability and metastatic potential.
  • E2A influences cancer behavior by regulating Snai1 transcription and is associated with poor outcomes in aggressive breast cancers, suggesting that targeting E2A could be a promising strategy in breast cancer therapy.
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Enzymes of the methionine and homocysteine metabolism catalyze reactions belonging to the methionine and folate cycles and the transsulfuration pathway. The importance of the metabolites produced through these routes (e.g.

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Background: The goal of this study was to determine if adenovirus-delivered LOXL2 protects against progressive knee osteoarthritis (OA), assess its specific mechanism of action; and determine if the overexpression of LOXL2 in transgenic mice can protect against the development of OA-related cartilage damage and joint disability.

Methods: Four-month-old Cho/+ male and female mice were intraperitoneally injected with either Adv-RFP-LOXL2 or an empty vector twice a month for four months. The proteoglycan levels and the expression of anabolic and catabolic genes were examined by immunostaining and qRT-PCR.

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The endoplasmic reticulum (ER) is the organelle where newly synthesized proteins enter the secretory pathway. Different physiological and pathological conditions may perturb the secretory capacity of cells and lead to the accumulation of misfolded and unfolded proteins. To relieve the produced stress, cells evoke an adaptive signalling network, the unfolded protein response (UPR), aimed at recovering protein homeostasis.

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Protein-protein interactions are an important mechanism for the regulation of enzyme function allowing metabolite channeling, crosstalk between pathways or the introduction of post-translational modifications. Therefore, a number of high-throughput studies have been carried out to shed light on the protein networks established under different pathophysiological settings. Surprisingly, this type of information is quite limited for enzymes of intermediary metabolism such as betaine homocysteine S-methyltransferase, despite its high hepatic abundancy and its role in homocysteine metabolism.

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Lysyl oxidase-like 3 (LOXL3) is a member of the lysyl oxidase family comprising multifunctional enzymes with depicted roles in extracellular matrix maturation, tumorigenesis, and metastasis. In silico expression analyses followed by experimental validation in a comprehensive cohort of human cell lines revealed a significant upregulation of LOXL3 in human melanoma. We show that LOXL3 silencing impairs cell proliferation and triggers apoptosis in various melanoma cell lines.

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The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth.

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Epithelial/mesenchymal transition (EMT) has emerged as a key regulator of metastasis by facilitating tumor cell invasion and dissemination to distant organs. Recent evidences support that the reverse mesenchymal/epithelial transition (MET) is required for metastatic outgrowth; moreover, the existence of hybrid epithelial/mesenchymal (E/M) phenotypes is increasingly being reported in different tumor contexts. The accumulated data strongly support that plasticity between epithelial and mesenchymal states underlies the dissemination and metastatic potential of carcinoma cells.

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Epithelial-to-Mesenchymal Transition (EMT) is a key process contributing to the aggressiveness of cancer cells. EMT is triggered by activation of different transcription factors collectively known as EMT-TFs. Different cellular cues and cell signalling networks activate EMT at transcriptional and posttranscriptional level in different biological and pathological situations.

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Methionine adenosyltransferases MAT I and MAT III (encoded by Mat1a) catalyze S-adenosylmethionine synthesis in normal liver. Major hepatic diseases concur with reduced levels of this essential methyl donor, which are primarily due to an expression switch from Mat1a towards Mat2a. Additional changes in the association state and even in subcellular localization of these isoenzymes are also detected.

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