Publications by authors named "Irene Gonzalez"

21 Publications

  • Page 1 of 1

MAOB rs3027452 Modifies Mood Improvement After Tryptophan Supplementation.

Int J Gen Med 2021 6;14:1751-1756. Epub 2021 May 6.

Department of Surgery, Biochemistry and Immunology School of Medicine, University of Malaga, Malaga, Spain.

Purpose: Tryptophan is the only precursor of serotonin, the hormone which helps regulate key human functions such as appetite, memory, mood, and sexual behavior. Connections have been identified between serotonin system dysfunction and the molecular etiology and treatment of mood disorders in a wide range of studies. Proposals have been put forward to co-administer tryptophan supplementation together with serotonin reuptake inhibitors in major depression patients, and also to exploit the sub-therapeutic depressive status in healthy populations. The reported responses, however, have been very dissimilar and this uneven effect may largely be explained by interindividual genetic differences.

Materials And Methods: We studied mood change in 138 healthy subjects using both Goldberg's General Health Questionnaire and the Profile of Mood States Questionnaire to determine the effects of a daily supplementation of 1g of tryptophan or placebo. Buccal DNA samples were provided and (rs1800532), (rs3788862 and rs979605), (rs3027452), and (rs6269 and rs4680) variants were genotyped.

Results: rs3027452 was equally associated with tryptophan supplementation efficacy in the depression subscales of both questionnaires (ΔT-Score.D; ΔT-Score.TMD and ΔPOMS.D p-values <0.01).

Conclusion: Here we provide evidence that tryptophan supplementation has an uneven effect on mood improvement in the general population.
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http://dx.doi.org/10.2147/IJGM.S305443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110250PMC
May 2021

Preoperative detection and evaluation of the need for psychological intervention in cancer and non-cancer patients referred to thoracic surgery.

Cir Esp (Engl Ed) 2021 May 7. Epub 2021 May 7.

Thoracic Surgery Service, Hospital Clínico San Carlos de Madrid, Departamento Cirugía, Universidad Complutense de Madrid, Madrid, Spain.

Objectives: (a) to evaluate and compare the psychological treatment needs of patients with cancer and non-cancer, who are going to undergo scheduled thoracic surgery, and (b) evaluate and compare the diagnostic accuracy of the screening tests of psychological treatment needs for cancer and non-cancer patients.

Method: The need for psychological treatment was evaluated in a total of 169 patients prior to thoracic surgery, through a clinical interview. The screening tests used were: the physician's judgment (yes/no), the Hospital Anxiety and Depression Scale (HADS) and, the single-item interview to assess depression "Do you feel depressed?" (DEPQ).

Results: The number of patients who needed psychological treatment in the total sample was 47 (27.81%), in non-cancer-patients: 22 (30.99%) and in cancer patients: 25 (25.51%). The participants with treatment needs were more often young women with primary education levels, with more fears and concerns regarding their disease. With respect to the screening tests, the HADS-T (cut-off point ≥13) obtained a sensitivity (SE) of 0.75 and Specificity (SP) of 0.81 in the total sample. In patients with cancer, the HADS total score (cut-off point ≥10) obtained an SE=0.84 and SP=0.80, and, in non-cancer patients, the HADS total score (cut-off point ≥13) showed an SE=0.59 and SP=0.84. The DEPQ and the physician's judgment did not achieve adequate levels of precision.

Conclusions: A high percentage of patients have psychological treatment needs before performing thoracic surgery, which are similar for cancer and non-cancer patients. Preoperative detection of patients who need psychological intervention is feasible with a simple screening test: HADS, which achieves greater precision in cancer patients.
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http://dx.doi.org/10.1016/j.ciresp.2021.03.010DOI Listing
May 2021

Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease 2019.

Anesth Analg 2021 01;132(1):25-30

From the Department of Anesthesiology and Intensive Care Medicine, Clinical University Hospital of Santiago, Santiago, Spain.

Background: In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) during mechanical ventilation for periods of 12-16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19.

Methods: The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collected: number and duration of PP sessions; tissue O2 saturation (StO2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient.

Results: Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval [CI], 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, -9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU.

Conclusions: We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.
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http://dx.doi.org/10.1213/ANE.0000000000005239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523477PMC
January 2021

Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model.

Sci Rep 2020 04 28;10(1):7166. Epub 2020 Apr 28.

Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.

Insulin-like growth factor-1 (IGF-1) has demonstrated beneficial effects after myocardial infarction (MI). Microencapsulation of IGF-1 could potentially improve results. We aimed to test the effect of an intracoronary (IC) infusion of microencapsulated IGF-1 in a swine acute MI model. For that purpose IC injection of a 10 ml solution of 5 × 10 IGF-1 loaded microspheres (MSPs) (n = 8, IGF-1 MSPs), 5 × 10 unloaded MSPs (n = 9; MSPs) or saline (n = 7; CON) was performed 48 hours post-MI. Left ventricular ejection fraction (LVEF), indexed ventricular volumes and infarct size (IS) were determined by cardiac magnetic resonance at pre-injection and 10 weeks. Animals were euthanized at 10 weeks, and myocardial fibrosis and vascular density were analysed. End-study LVEF was significantly greater in IGF-1 MSPs compared to MSPs and CON, while ventricular volumes exhibited no significant differences between groups. IS decreased over time in all groups. Collagen volume fraction on the infarct area was significantly reduced in IGF-1 MSPs compared to CON and MSPs. Vascular density analysis of infarct and border zones showed no significant differences between groups. In conclusion, the IC injection of 5 × 10 IGF-1 loaded MSPs in a porcine acute MI model successfully improves cardiac function and limits myocardial fibrosis, which could be clinically relevant.
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http://dx.doi.org/10.1038/s41598-020-64097-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188803PMC
April 2020

Author Correction: The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction.

Stem Cell Rev Rep 2020 06;16(3):626

Stem Cell Therapy Unit, Jesus Uson Minimally Invasive Surgery Centre, Cáceres, Spain.

The original version of this article unfortunately contained a mistake. In the author group, the correct family name of Dr. Rebeca is "Blázquez" and the correct family name of Dr. Francisco Miguel is "Sánchez-Margallo."
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http://dx.doi.org/10.1007/s12015-020-09962-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645569PMC
June 2020

The Intrapericardial Delivery of Extracellular Vesicles from Cardiosphere-Derived Cells Stimulates M2 Polarization during the Acute Phase of Porcine Myocardial Infarction.

Stem Cell Rev Rep 2020 06;16(3):612-625

Stem Cell Therapy Unit, Jesus Uson Minimally Invasive Surgery Centre, Cáceres, Spain.

Acute myocardial infarction triggers a strong inflammatory response in the affected cardiac tissue. New therapeutic tools based on stem cell therapy may modulate the unbalanced inflammation in the damaged cardiac tissue, contributing to the resolution of this pathological condition. The main goal of this study was to analyze the immunomodulatory effects of cardiosphere-derived cells (CDCs) and their extracellular vesicles (EV-CDCs), delivered by intrapericardial administration in a clinically relevant animal model, during the initial pro-inflammatory phase of an induced myocardial infarction. This effect was assessed in peripheral blood and pericardial fluid leukocytes from infarcted animals. Additionally, cardiac functional parameters, troponin I, hematological and biochemical components were also analyzed to characterize myocardial infarction-induced changes, as well as the safety aspects of these procedures. Our preclinical study demonstrated a successful myocardial infarction induction in all animals, without any reported adverse effect related to the intrapericardial administration of CDCs or EV-CDCs. Significant changes were observed in biochemical and immunological parameters after myocardial infarction. The analysis of peripheral blood leukocytes revealed an increase of M2 monocytes in the EV-CDCs group, while no differences were reported in other lymphocyte subsets. Moreover, arginase-1 (M2-differentiation marker) was significantly increased in pericardial fluids 24 h after EV-CDCs administration. In summary, we demonstrate that, in our experimental conditions, intrapericardially administered EV-CDCs have an immunomodulatory effect on monocyte polarization, showing a beneficial effect for counteracting an unbalanced inflammatory reaction in the acute phase of myocardial infarction. These M2 monocytes have been defined as "pro-regenerative cells" with a pro-angiogenic and anti-inflammatory activity.
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http://dx.doi.org/10.1007/s12015-019-09926-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253530PMC
June 2020

Beyond Broadway: Analysis of Qualitative Characteristics of and Individual Responses to Creatively Able, a Music and Movement Intervention for Children with Autism.

Int J Environ Res Public Health 2019 04 17;16(8). Epub 2019 Apr 17.

Clare Trevor School of Arts, University of California, Irvine, CA 92617, USA.

Movement in response to music represents one of the natural social environments in which physical activity occurs. The study of music and movement, including dance, requires a careful, holistic consideration of many features, which may include music, physical activity, motor learning, social engagement, emotion, and creativity. The overarching goal of this manuscript is to examine qualitative characteristics of and individual responses to a music and movement intervention (Creatively Able) for children with Autism Spectrum Disorder (ASD). We provide a description of Creatively Able, illustrating how the program design and physical and social environment were informed by children's needs and preferences in order to provide an enriched environment in which to promote multiple systems in children with ASD. Using data from two pilot studies with 20 children with ASD, we illustrate how researchers can use observational research methods to measure important aspects of the social environment (e.g., children's engagement during intervention sessions) as well as engagement of potential underlying behavioral mechanisms (e.g., self-regulation) that might reduce clinical symptoms. We further illustrate how individual responses to intervention (e.g., improvements in behaviors or symptoms) can be studied in physically active interventions. Our pilot study results showed group-level reductions in Stereotyped and Compulsive behaviors of 8% and 4%, respectively; posthoc analysis revealed that there were substantial individual differences in children's responses to the intervention. This research illustrates robust methods that can be applied to intervention research to improve our understanding of important features of interventions that might help promote development in various domains, including executive functions and self-regulation.
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http://dx.doi.org/10.3390/ijerph16081377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517971PMC
April 2019

Dysmorphic contribution of neurotransmitter and neuroendocrine system polymorphisms to subtherapeutic mood states.

Brain Behav 2019 02 17;9(2):e01140. Epub 2019 Jan 17.

Department of Surgery, Biochemistry and Immunology, School of Medicine, University of Malaga, Malaga, Spain.

Objective: From an evolutionary perspective, emotions emerged as rapid adaptive reactions that increase survival rates. Current psychobiology includes the consideration that genetic changes affecting neuroendocrine and neurotransmission pathways may also be affecting mood states. Following this hypothesis, abnormal levels of any of the aminergic neurotransmitters would be of considerable importance in the development of a pathophysiological state.

Materials And Methods: A total of 668 students from the School of Medicine of the University of Malaga (Average = 22.41 ± 3; 41% men) provided self-report measures of mood states using POMS and GHQ-28 questionnaires and buccal cells for genotyping 19 polymorphisms from 14 selected neurotransmitter pathways genes (HTR1A; HTR2A; HTR2C; HTR3B; TPH1; SLC18A1; SLC18A2; COMT; MAOA; MAOB) and neuroendocrine system (AVPR1B; OPRM1; BDNF; OXTR).

Results: MAOA rs3788862 genotype correlates with decreasing levels of Tension among females (beta = -0.168, p-value = 0.003) but it is neutral among males in this subscale. On the contrary, it correlates with lower GHQ-28 depression scores among males (beta = -0.196, p-value = 0.008). Equivalently, SLC18A1 and HTR2A variants correlated with anger and vigor scores, only among males. From the neuroendocrine system, OPRM1 rs1799971 correlated increasing levels of female's Anxiety, depression and Social Dysfunction scores.

Conclusion: Our findings suggest that these polymorphisms contribute to define general population mood levels, although exhibiting a clear sexual dimorphism.
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http://dx.doi.org/10.1002/brb3.1140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379594PMC
February 2019

Varicella-zoster virus clades circulating in Spain over two decades.

J Clin Virol 2019 01 28;110:17-21. Epub 2018 Nov 28.

Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Spain. Electronic address:

Background: Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain.

Objectives: To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016.

Study Design: In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs.

Results: Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001).

Conclusions: Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.
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http://dx.doi.org/10.1016/j.jcv.2018.11.008DOI Listing
January 2019

Aging-related tau astrogliopathy (ARTAG): not only tau phosphorylation in astrocytes.

Brain Pathol 2018 11 25;28(6):965-985. Epub 2018 Feb 25.

Ministry of Economy and Competitiveness, CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, Barcelona, Spain.

Aging-related tau astrogliopathy (ARTAG) is defined by the presence of two types of tau-bearing astrocytes: thorn-shaped astrocytes (TSAs) and granular/fuzzy astrocytes in the brain of old-aged individuals. The present study is focused on TSAs in rare forms of ARTAG with no neuronal tau pathology or restricted to entorhinal and transentorhinal cortices, to avoid bias from associated tauopathies. TSAs show 4Rtau phosphorylation at several specific sites and abnormal tau conformation, but they lack ubiquitin and they are not immunostained with tau-C3 antibodies which recognize truncated tau at Asp421. Astrocytes in ARTAG have atrophic processes, reduced glial fibrillary acidic protein (GFAP) and increased superoxide dismutase 2 (SOD2) immunoreactivity. Gel electrophoresis and western blotting of sarkosyl-insoluble fractions reveal a pattern of phospho-tau in ARTAG characterized by two bands of 68 and 64 kDa, and several middle bands between 35 and 50 kDa which differ from what is seen in AD. Phosphoproteomics of dissected vulnerable regions identifies an increase of phosphorylation marks in a large number of proteins in ARTAG compared with controls. GFAP, aquaporin 4, several serine-threonine kinases, microtubule associated proteins and other neuronal proteins are among the differentially phosphorylated proteins in ARTAG thus suggesting a hyper-phosphorylation background that affects several molecules, including many kinases and proteins from several cell compartments and various cell types. Finally, present results show for the first time that tau seeding is produced in neurons of the hippocampal complex, astrocytes, oligodendroglia and along fibers of the corpus callosum, fimbria and fornix following inoculation into the hippocampus of wild type mice of sarkosyl-insoluble fractions enriched in hyper-phosphorylated tau from selected ARTAG cases. These findings show astrocytes as crucial players of tau seeding in tauopathies.
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http://dx.doi.org/10.1111/bpa.12593DOI Listing
November 2018

Pregnancy after bariatric surgery: improving outcomes for mother and child.

Int J Womens Health 2016 14;8:721-729. Epub 2016 Dec 14.

Endocrinology and Nutrition Department, Hospitales Universitarios Virgen del Rocío, Seville, Spain.

The significant increase in the prevalence of obesity has led to an increase in the number of obese women who become pregnant. In this setting, in recent years, there has been an exponential rise in the number of bariatric procedures, with approximately half of them performed in women of childbearing age, and a remarkable surge in the number of women who become pregnant after having undergone bariatric surgery (BS). These procedures entail the risk of nutritional deficiencies, and nutrition is a crucial aspect during pregnancy. Therefore, knowledge and awareness of the consequences of these techniques on maternal and fetal outcomes is essential. Current evidence suggests a better overall obstetric outcome after BS, in comparison to morbid obese women managed conservatively, with a reduction in the prevalence of gestational diabetes mellitus, pregnancy-associated hypertensive disorders, macrosomia, and congenital defects. However, the risk of potential maternal nutritional deficiencies and newborns small for gestational age cannot be overlooked. Results concerning the incidence of preterm delivery and the number of C-sections are less consistent. In this paper, we review the updated evidence regarding the impact of BS on pregnancy.
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http://dx.doi.org/10.2147/IJWH.S99970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167470PMC
December 2016

Genome and transcriptome analysis of the Mesoamerican common bean and the role of gene duplications in establishing tissue and temporal specialization of genes.

Genome Biol 2016 Feb 25;17:32. Epub 2016 Feb 25.

Environmental Biology Department, Centro de Investigaciones Biológicas, (CSIC), 28040, Madrid, Spain.

Background: Legumes are the third largest family of angiosperms and the second most important crop class. Legume genomes have been shaped by extensive large-scale gene duplications, including an approximately 58 million year old whole genome duplication shared by most crop legumes.

Results: We report the genome and the transcription atlas of coding and non-coding genes of a Mesoamerican genotype of common bean (Phaseolus vulgaris L., BAT93). Using a comprehensive phylogenomics analysis, we assessed the past and recent evolution of common bean, and traced the diversification of patterns of gene expression following duplication. We find that successive rounds of gene duplications in legumes have shaped tissue and developmental expression, leading to increased levels of specialization in larger gene families. We also find that many long non-coding RNAs are preferentially expressed in germ-line-related tissues (pods and seeds), suggesting that they play a significant role in fruit development. Our results also suggest that most bean-specific gene family expansions, including resistance gene clusters, predate the split of the Mesoamerican and Andean gene pools.

Conclusions: The genome and transcriptome data herein generated for a Mesoamerican genotype represent a counterpart to the genomic resources already available for the Andean gene pool. Altogether, this information will allow the genetic dissection of the characters involved in the domestication and adaptation of the crop, and their further implementation in breeding strategies for this important crop.
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http://dx.doi.org/10.1186/s13059-016-0883-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766624PMC
February 2016

Arterioportal fistula, a rare cause of presinusoidal portal hypertension.

Gastroenterol Hepatol 2016 Jan 21;39(1):43-5. Epub 2015 Jul 21.

Puerta de Hierro University Hospital, IBD Unit, Gastroenterology and Hepatology Department, Calle Manuel de Falla, 1, Madrid, Spain.

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http://dx.doi.org/10.1016/j.gastrohep.2015.04.010DOI Listing
January 2016

Maternal and perinatal outcomes after bariatric surgery: a Spanish multicenter study.

Obes Surg 2015 Mar;25(3):436-42

Hospital Juan Ramón Jiménez, Ronda Exterior Norte s/n 21005, Huelva, Spain,

Background: Bariatric surgery (BS) has become more frequent among women of child-bearing age. Data regarding the underlying maternal and perinatal risks are scarce. The objective of this nationwide study is to evaluate maternal and perinatal outcomes after BS.

Methods: We performed a retrospective observational study of 168 pregnancies in 112 women who underwent BS in 10 tertiary hospitals in Spain over a 15-year period. Maternal and perinatal outcomes, including gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders (PAHD), pre-term birth cesarean deliveries, small and large for gestational age births (SGA, LGA), still births, and neonatal deaths, were evaluated. Results were further compared according to the type of BS performed: restrictive techniques (vertical-banded gastroplasty, sleeve gastrectomy, and gastric banding), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD).

Results: GDM occurred in five (3 %) pregnancies and there were no cases of PAHD. Women whose pregnancies occurred before 1 year after BS had a higher pre-gestational body mass index (BMI) than those who got pregnant 1 year after BS (34.6 ± 7.7 vs 30.4 ± 5.3 kg/m(2), p = 0.007). In pregnancies occurring during the first year after BS, a higher rate of stillbirths was observed compared to pregnancies occurring after this period of time (35.5 vs 16.8 %, p = 0.03). Women who underwent BPD delivered a higher rate of SGA babies than women with RYGB or restrictive procedures (34.8, 12.7, and 8.3 %, respectively).

Conclusions: Pregnancy should be scheduled at least 1 year after BS. Malabsorptive procedures are associated to a higher rate of SGA births.
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http://dx.doi.org/10.1007/s11695-014-1387-7DOI Listing
March 2015

Genomic analysis of the blood attributed to Louis XVI (1754-1793), king of France.

Sci Rep 2014 Apr 24;4:4666. Epub 2014 Apr 24.

Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Dr. Aiguader 88, 08003 Barcelona, Spain.

A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754-1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (~2.5×) with coding sequences enriched at a higher ~7.3× coverage. We found that the ancestry of the gourd's genome does not seem compatible with Louis XVI's known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king.
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http://dx.doi.org/10.1038/srep04666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998215PMC
April 2014

Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-кB target genes in human breast cancer.

Oncotarget 2014 Jan;5(1):196-210

Cancer Research Program, IMIM (Hospital del Mar Research Institute), Barcelona, Spain.

NF-кB has been linked to doxorubicin resistance in breast cancer patients. NF-кB nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined; however its functional relevance at transcriptional level on NF-кB-dependent genes and the biological consequences are unclear. We studied NF-кB-dependent gene expression induced by doxorubicin in breast cancer cells and fresh human cancer specimens with different genetic backgrounds focusing on their p53 status. NF-кB-dependent signature of doxorubicin was identified by gene expression microarrays in breast cancer cells treated with doxorubicin and the IKKβ-inhibitor MLN120B, and confirmed ex vivo in human cancer samples. The association with p53 was functionally validated. Finally, NF-кB activation and p53 status was determined in a cohort of breast cancer patients treated with adjuvant doxorubicin-based chemotherapy. Doxorubicin treatment in the p53-mutated MDA-MB-231 cells resulted in NF-кB driven-gene transcription signature. Modulation of genes related with invasion, metastasis and chemoresistance (ICAM-1, CXCL1, TNFAIP3, IL8) were confirmed in additional doxorubicin-treated cell lines and fresh primary human breast tumors. In both systems, p53-deficient background correlated with the activation of the NF-кB-dependent signature. Furthermore, restoration of p53WT in the mutant p53 MDA-MB-231 cells impaired NF-кB driven transcription induced by doxorubicin. Moreover, a p53 deficient background and nuclear NF-кB/p65 in breast cancer patients correlated with reduced disease free-survival. This study supports that p53 deficiency is necessary for a doxorubicin driven NF-кB-response that limits doxorubicin cytotoxicity in breast cancer and is linked to an aggressive clinical behavior.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960201PMC
http://dx.doi.org/10.18632/oncotarget.1556DOI Listing
January 2014

Uterine NK cells are critical in shaping DC immunogenic functions compatible with pregnancy progression.

PLoS One 2012 8;7(10):e46755. Epub 2012 Oct 8.

Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Laboratory of Reproductive Medicine, Berlin, Germany.

Dendritic cell (DC) and natural killer (NK) cell interactions are important for the regulation of innate and adaptive immunity, but their relevance during early pregnancy remains elusive. Using two different strategies to manipulate the frequency of NK cells and DC during gestation, we investigated their relative impact on the decidualization process and on angiogenic responses that characterize murine implantation. Manipulation of the frequency of NK cells, DC or both lead to a defective decidual response characterized by decreased proliferation and differentiation of stromal cells. Whereas no detrimental effects were evident upon expansion of DC, NK cell ablation in such expanded DC mice severely compromised decidual development and led to early pregnancy loss. Pregnancy failure in these mice was associated with an unbalanced production of anti-angiogenic signals and most notably, with increased expression of genes related to inflammation and immunogenic activation of DC. Thus, NK cells appear to play an important role counteracting potential anomalies raised by DC expansion and overactivity in the decidua, becoming critical for normal pregnancy progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046755PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466312PMC
May 2013

Development and validation with clinical samples of internally controlled multiplex real-time PCR for diagnosis of BKV and JCV infection in associated pathologies.

Comp Immunol Microbiol Infect Dis 2012 Mar 17;35(2):173-9. Epub 2012 Jan 17.

Viral Isolation and Detection Laboratory, Microbiology Diagnostic Service, National Microbiology Centre, Carlos III Health Institute, Majadahonda, Madrid, Spain.

This article describes the development and validation with clinical samples of an internally controlled multiplex quantitative real-time PCR (QRT-PCR) for human polyomaviruses BK (BKV) and JC (JCV). Blood and urine samples from renal transplant recipients with suspected nephropathy, and cerebrospinal fluid (CSF) specimens from AIDS, natalizumab-treated and HIV-negative patients with suspected progressive multifocal leukoencephalopathy, previously checked for BKV and JCV by conventional PCR, were tested by QRT-PCR. All samples positive by conventional PCR were confirmed by QRT-PCR. Four cases of JCV-associated neurological infection, including all those detected in natalizumab-treated patients, and one case of BKV-related neurological infection were only identified by QRT-PCR. BKV was quantified in the CSF of neurological patients for the first time. Analyses of the Quality Control for Molecular Diagnostics 2010 panel were "highly satisfactory" for BKV and "satisfactory" for JCV. The QRT-PCR is specific and reproducible. It improves the sensitivity of conventional PCR for the diagnosis of BKV and JCV infection in various diseases.
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http://dx.doi.org/10.1016/j.cimid.2011.12.010DOI Listing
March 2012

Angiotensin II induces MMP 2 activity via FAK/JNK pathway in human endothelial cells.

Biochem Biophys Res Commun 2009 Mar 29;380(4):769-74. Epub 2009 Jan 29.

Departamento de Bioquímica y Biología Molecular, Universidad de Málaga, Boulevard Louis Pasteur 32, 29071 Málaga, Spain.

Matrix metalloproteinases (MMPs) play an important role in the pathogenesis of cardiovascular diseases and are modified in response to a variety of stimuli such as bioactive peptides, cytokines and/or grown factors. In this study, we demonstrated that angiotensin II (Ang II) induces a time- and dose-dependent increase in the activity of metalloproteinase 2 (MMP 2) in human umbilical vein endothelial cells (HUVEC). The effect of Ang II was markedly attenuated in cells pretreated with wortmannin and LY294002, two selective inhibitors of phosphatidylinositol-3-kinase (PI3K), indicating that PI3K plays a key role in regulating MMP 2 activity. Similar results were observed when HUVEC were pretreated with genistein, a non-selective tyrosine kinases inhibitor, or with the specific Src-family tyrosine kinase inhibitor PP2, demonstrating the involvement of protein tyrosine kinases, and particularly Src-family tyrosine kinases on the downstream signaling pathway of Ang II receptors. Furthermore, Ang II-induced MMP 2 activation was markedly blocked by SP600125, a selective c-Jun N-terminal kinase (JNK) inhibitor, or pre-treatment of cells with antisense oligonucleotide to focal adhesion kinase (FAK), indicating that both molecules were important for the activation of MMP 2 by Ang II receptor stimulation. In conclusion, these results suggest that Ang II mediates an increase in MMP 2 activity in macrovascular endothelial cells through signal transduction pathways dependent on PI3K and Src-family tyrosine kinases activation, as well as JNK and FAK phosphorylation.
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http://dx.doi.org/10.1016/j.bbrc.2009.01.142DOI Listing
March 2009

Molecular epidemiological study of HEV-B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006.

J Med Virol 2008 Jun;80(6):1018-24

National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

Human enteroviruses are one of the main etiological agents of aseptic meningitis and other central nervous system infections, particularly the serotypes included in the enterovirus B species. Molecular methods have proved useful to identify serotypes in clinical samples, facilitating the epidemiological study of these viruses. In the spring of 2006, there was a significant increase in meningitis cases caused by enteroviruses in Spain. In the present study, 138 enteroviruses directly detected in clinical samples of patients with aseptic meningitis (n = 116) and other neurological pathologies (n = 22) received by the National Center for Microbiology during the year, were genotyped by amplification and sequencing part of the VP1 region and phylogenetic analysis. Echovirus 30 was the most frequent serotype, followed in decreasing order by echovirus 6, 9, 13, 18, enterovirus 75, coxsackievirus A9, echovirus 11, 14, 29, 4, and coxsackievirus B4 and B5. Phylogenetic analysis with all Spanish echovirus 30 strains detected in 2006 and other reported echovirus 30 sequences, demonstrated that Spanish strains formed a new lineage, different from others previously described. In conclusion, echovirus 30 is the most commonly reported enterovirus serotype associated with aseptic meningitis in Spain. Direct molecular typing of clinical samples also allows rapid identification of the serotypes involved in an epidemic alert and phylogenetic analysis in the 3'-VP1 region is useful to study viral epidemiology.
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http://dx.doi.org/10.1002/jmv.21197DOI Listing
June 2008