Javier Escobar - Academia.edu (original) (raw)

Papers by Javier Escobar

European Neuropsychopharmacology, 2019

The American Journal of Human Genetics, 2018

Most population isolates examined to date were founded from a single ancestral population. Conseq... more Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16 th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 363. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.

EKAIA Euskal Herriko Unibertsitateko Zientzi eta Teknologi Aldizkaria, 2016

2013ko maiatzaren 18an, APAk (Amerikar Psikiatria Elkartea), gaixotasun mentalen diagnostiko eta ... more 2013ko maiatzaren 18an, APAk (Amerikar Psikiatria Elkartea), gaixotasun mentalen diagnostiko eta estatistikaren bosgarren eskuliburua «Diagnostic and Statistical Manual of Mental Disorders (DSM-5») publikatu zuen. Eskuliburuaren hirugarren sailean (Neurketa tresna eta eredu berriak), DSM-5eko nortasunaren eta nortasun-nahasteen lan taldeak nortasunaren psikopatologiaren ebaluazio eta diagnostikoan birformulatze esanguratsua gomendatu du. Ikerketa honen bitartez, tresna berri horiek balidatu ditugu Euskal Herrian hartutako lagin batean. Euskal Herriak herrialde elebiduna izatearen berezitasuna dauka; horregatik nabaria da tresna hauek euskarara itzultzearen garrantzia, batez ere, euskara ama-hizkuntza duten ebaluatzaile eta gaixoentzat.

2014 IEEE 57th International Midwest Symposium on Circuits and Systems (MWSCAS), 2014

This paper shows a novel capacity to digital measurement circuit that is suited for differential ... more This paper shows a novel capacity to digital measurement circuit that is suited for differential MEMS capacitive sensors such as pressure sensors or condenser microphones. The basic operating principle relies on two differential reactance-controlled multivibrator circuits whose frequency differences are sensed by a Time to Digital Converter. The multivibrator oscillators may be biased in the relaxation oscillation mode, where demodulated flicker noise is greatly attenuated by large scale excitation of CMOS transistors. The paper shows a system level description of the readout circuit, a full transistor design in 0.13u CMOS and an oscillator characterization form measurements on a discrete demonstration circuit.

Mental Health Services Research, 2002

Ethnic minorities have relatively similar rates of mood disorders as do white Americans, but they... more Ethnic minorities have relatively similar rates of mood disorders as do white Americans, but they are much less likely to receive appropriate care. Barriers to care include lack of insurance, few minority providers&amp;#39; racism, and distrust of care providers. A priority in research is identifying practice interventions and policies that could eliminate disparities in care.

Free Radical Biology and Medicine, 2014

Oxidative and nitrosative stress cause changes in proteins which can alter their structure and/or... more Oxidative and nitrosative stress cause changes in proteins which can alter their structure and/or function. However, these changes especially in specific amino acid residues have proven to be reliable biomarkers of oxidative stress and inflammation. The aim of this study was to develop and validate a rapid method for the quantification of five selected biomarkers orto-tyrosine (o-tyr), meta-tyrosine (m-tyr), 3NO2-tyrosine (3NO2-tyr), 3I-tyrosine (3I-tyr) and 3Chloro-tyrosine (3Cl-tyr) in liver, brain and plasma, thus providing a snapshot of the oxidative stress status of the organism. The extraction and cleanup method entails protein precipitation, followed by digestion with pronase. Biomarker quantification is carried out using an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry employing positive electrospray ionization and a reversed phase chromatographic separation. Liver, brain and plasma samples from hypoxic (FiO2: 8%) vs. normoxic newborn piglets (n=5) were studied employing the developed analytical method. m-tyrosine/phenylalanine, orto-tyrosine/phenylalanine, 3Cl-tyrosine/p-tyrosine and 3I-tyrosine/p-tyrosine ratios in liver of hypoxic animals were significantly increased as compared to normoxic. Although no significant differences were found for brain and plasma samples, a clear tendency to increased ratios was observed under hypoxic conditions. This analytical tool has proofed its suitability for the analysis of tissue and plasma samples from newborn piglets. The analysis of biomarkers of protein oxidation in bigger cohorts will be the topic of future studies with the aim of gaining a deeper insight into the mechanisms of oxidation-derived protein modification caused during hypoxia.

Psychiatric Services, 2007

This article reports on the outcome of an expert consensus meeting in August 2005 sponsored by th... more This article reports on the outcome of an expert consensus meeting in August 2005 sponsored by the National Institute of Mental Health, which assembled 15 senior researchers with a background in treatment and services research with the Hispanic population. The purpose of the workshop was to identify research issues most pertinent for improving quality and effectiveness of treatment for Hispanics experiencing persistent mental disorders, defined as psychiatric syndromes that are of sufficient severity and duration to cause long-term impairment in social and occupational functioning and significant disability. The spectrum of ideas and recommendations advanced at the one-day meeting was wide and overlapping; therefore, the rich body of material was subsequently organized into five topics: diagnosis, quality of care and culturally appropriate services, psychosocial intervention development, psychopharmacologic interventions, and access to care. Although the authors recognize that the review was broad and the agenda presented is ambitious and in many instances generalizes to priority areas in overall mental health services and treatment research, the recommendations are intended to stimulate research for addressing the unique problems and research deficits that affect Hispanics with persistent mental disorders.

The Journal of Maternal-Fetal & Neonatal Medicine, 2012

Talanta, 2014

Liquid chromatography-mass spectrometry (LC-MS) has been increasingly used in biomedicine to stud... more Liquid chromatography-mass spectrometry (LC-MS) has been increasingly used in biomedicine to study the dynamic metabolomic responses of biological systems under different physiological or pathological conditions. To obtain an integrated snapshot of the system, metabolomic methods in biomedicine typically analyze biofluids (e.g. plasma) that require clean-up before being injected into LC-MS systems. However, high resolution LC-MS is costly in terms of resources required for sample and data analysis and care must be taken to prevent chemical (e.g. ion suppression) or statistical artifacts. Because of that, the effect of sample preparation on the metabolomic profile during metabolomic method development is often overlooked. This work combines an Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) and a multivariate exploratory data analysis for a cost-effective qualitative evaluation of major changes in sample composition during sample preparation. ATR-FTIR and LC-time of flight mass spectrometry (TOFMS) data from the analysis of a set of plasma samples precipitated using acetonitrile, methanol and acetone performed in parallel were used as a model example. Biochemical information obtained from the analysis of the ATR-FTIR and LC-TOFMS data was thoroughly compared to evaluate the strengths and shortcomings of FTIR biospectroscopy for assessing sample preparation in metabolomics studies. Results obtained show the feasibility of ATR-FTIR for the evaluation of major trends in the plasma composition changes among different sample pretreatments, providing information in terms of e.g., amino acids, proteins, lipids and carbohydrates overall contents comparable to those found by LC-TOFMS.

World journal of gastrointestinal pharmacology and therapeutics, Jan 6, 2010

Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory resp... more Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of pro-inflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatin modifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive element (CRE) and the transcription factor CRE-binding protein (CREB). CREB can be phosphorylated and activated by different kinases, such as protein kinase A and MAPK, and then it recruits the histone acetyltransferase co-activator CREB-binding protein (CBP) and its homologue p300. The recruitment of ...

Psychopharmacology, 2003

Rationale: This article is intended to explore how minority status and cultural factors affect th... more Rationale: This article is intended to explore how minority status and cultural factors affect the participation of subjects in clinical psychopharmacology research. Objectives and methods: A literature review was performed using key words "clinical psychopharmacology trials", "psychiatric ethics" and "minority groups". Major goals of this review were to examine current knowledge base and identify existing gaps in this fairly new area of psychiatric research. Results: We found extremely few papers addressing the issue directly. Most references to minority groups were made peripherally, and many of these were extrapolated to psychiatric patients from work done on medical populations. We found no empirical studies done in psychiatric populations. Conclusions: Systematic, well-designed research studies are needed to elucidate how culture, race and ethnicity impact on such issues as accrual, retention, informed consent and safeguards against the potential exploitation of minority research subjects. On the basis of the literature review and our personal experience doing clinical research with minority patients, we provide several recommendations and specific suggestions to clinical researchers who include minority patients in their clinical trials.

Pediatric Research, 2012

Articles Translational Investigation nature publishing group Background: chronic exposure to supp... more Articles Translational Investigation nature publishing group Background: chronic exposure to supplemental oxygen (O 2) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature. Methods: Following 1-h 100% O 2 exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated. results: superoxide dismutase 3 (sOD3) expression in female pups' lungs was increased as compared with that in the lungs of male pups. as compared with air-treated pups, the response of male pups to thromboxane was increased by O 2 , whereas the opposite effect was documented in the vessels of female pups. The enhanced force of hyperoxia-exposed arteries of the male pups was suppressed with superoxide or peroxynitrite scavengers, and increased lung sOD activity and hydrogen peroxide content were seen in female, but not in male, rats. hyperoxia induced an increase in lung tissue oxidative products and Rho-kinase (ROcK) activity in male, but not in female, pups. conclusion: a lower lung sOD content and failure to upregulate sOD activity facilitates peroxynitrite generation and ROcK activation in hyperoxia-exposed males, predisposing them to pulmonary vasoconstriction. These observations, if relevant to humans, may explain the increased mortality and higher incidence of pulmonary hypertension in male neonates.

Pancreatology, 2012

s / Pancreatology 12 (2012) 502–597 538 interference of Sam68 and SRSF1 expression cause a partia... more s / Pancreatology 12 (2012) 502–597 538 interference of Sam68 and SRSF1 expression cause a partial recovery of drug sensitivity. Conclusions: Our results show that chronic exposure of PDAC cells to gemcitabine leads to selection of a drug-resistant subpopulation overexpressing Sam68 and SRSF1. Importantly, the depletion of these proteins leads to a partial recovery of the sensibility to gemcitabine, suggesting that they may represent suitable molecular-targets to overcome drug resistance in PDAC. Arumugam T, Ramachandran V, Fournier KF, et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res. 2009 Jul Shapiro IM, Cheng AW, Flytzanis NC, et al. An EMT-driven alternative splicing program occurs in human breast cancer and modulates cellular phenotype. PLoS Genet. 2011 Ghigna C, De Toledo M, Bonomi S, et al. Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: therapeutic potential of bifunctional oligonucleotides and indole derivatives. RNA Biol. 2010 Valacca C, Bonomi S, Buratti E, et al. Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J Cell Biol. 2010

Neonatology, 2013

Background: In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes ... more Background: In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF). Objectives: We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced by the concentration of specific biomarkers in AF. Material and Methods: 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively. Results: The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 ...

Mental Health, Religion & Culture, 2011

The purpose of this cross-sectional study was to explore causal attributions about depression and... more The purpose of this cross-sectional study was to explore causal attributions about depression and to identify psychosocial factors associated with these beliefs among Latino immigrants. We interviewed 177 primary care patients with instruments to assess causal beliefs, depressive and somatic symptoms, ethnic identity and stigma. An exploratory factor analysis of the Causal Beliefs scale yielded three factors, “Balance,” “Psychosocial” and

Journal of Transcultural Nursing, 2012

Purpose: This study describes causal beliefs about depression among Dominican, Colombian, and Ecu... more Purpose: This study describes causal beliefs about depression among Dominican, Colombian, and Ecuadorian immigrants. The authors describe participants’ narratives about how particular supernatural or religious beliefs may contribute to or alleviate depression. Method: Latino primary care patients ( n = 177) were interviewed with the Beliefs About Causes of Depression Scale, a list of 35 items rated from not at all important to extremely important. Participants had the option of expanding on responses using an informal conversational approach. Underlying themes of these explanatory comments were derived from narrative and content analysis. Results: Major themes that emerged were Psychosocial and Religious and Supernatural causal beliefs. A third theme emerged that represented the integration of these categories in the context of the immigrant experience. Discussion and Conclusions: This article adds to the understanding of cross-cultural beliefs about depression. Psychosocial stresso...

Journal of Pharmacology and Experimental Therapeutics, 2009

Mitogen activated protein kinases (MAPK) are considered major signal transducers early during the... more Mitogen activated protein kinases (MAPK) are considered major signal transducers early during the development of acute pancreatitis. Pentoxifylline is a phosphodiesterase inhibitor with marked anti-inflammatory properties through blockade of ERK phosphorylation and TNF-alpha production. Our aim was to elucidate the mechanism of action of pentoxifylline as anti-inflammatory agent in acute pancreatitis. Necrotizing pancreatitis induced by taurocholate in rats and taurocholate-treated AR42J acinar cells were studied. Phosphorylation of ERK and MEK1/2, as well as PP2A, PP2B and PP2C serine threonine phosphatase activities, up-regulation of pro-inflammatory genes (by RT-PCR and chromatin immunoprecipitation) and recruitment of transcription factors and histone acetyltransferases/deacetylases to promoters of pro-inflammatory genes (egr-1,atf-3, inos, icam, il-6, tnf-α) were determined in pancreas during pancreatitis. Pentoxifylline did not reduce MEK1/2 phosphorylation but prevented the marked loss of serine threonine phosphatase PP2A activity induced by taurocholate in vivo without affecting PP2B and PP2C activities. The rapid loss in PP2A activity induced by taurocholate in acinar cells was due to a decrease in cAMP levels which was prevented by pentoxifylline. Pentoxifylline also reduced the induction of early (egr-1, atf-3) responsive genes and abrogated the up-regulation of late (inos, icam, il-6, tnf-α) responsive genes as well as recruitment of transcription factors (NF-κB and C/BPβ) and histone acetyltransferases to their gene promoters during pancreatitis. In conclusion, the beneficial effects of pentoxifylline-and presumably of other phosphodiesterase inhibitors-in this disease seem to be mediated by abrogating the loss of cAMP levels and PP2A activity as well as chromatin modifying complexes very early during acute pancreatitis.