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1.  Alteration in mitochondrial Ca2+ uptake disrupts insulin signaling in hypertrophic cardiomyocytes 
Background
Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca2+ release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood.
Results
In the present study we investigated insulin-dependent mitochondrial Ca2+ signaling in normal and norepinephrine or insulin like growth factor–1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca2+-fluorescent probes we showed that insulin increases mitochondrial Ca2+ levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca2+ uniporter, as well as by siRNA-dependent mitochondrial Ca2+ uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor–1-stimulated cells. This resulted in a reduction in mitochondrial Ca2+ uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca2+ uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling.
Conclusions
Mitochondrial Ca2+ uptake is a key event in insulin signaling and metabolism in cardiomyocytes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12964-014-0068-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12964-014-0068-4
PMCID: PMC4234850  PMID: 25376904
Insulin; Calcium; Mitochondria; Cardiac hypertrophy; Inositol 1,4,5-triphosphate receptor; Akt; IGF-1; Catecholamines
2.  Genome Sequence of Vibrio cholerae Strain O1 Ogawa El Tor, Isolated in Mexico, 2013 
Genome Announcements  2014;2(5):e01123-14.
We present the draft genome sequence of Vibrio cholerae InDRE 3140 recovered in 2013 during a cholera outbreak in Mexico. The genome showed the Vibrio 7th pandemic islands VSP1 and VSP2, the pathogenic islands VPI-1 and VPI-2, the integrative and conjugative element SXT/R391 (ICE-SXT), and both prophages CTXφ and RS1φ.
doi:10.1128/genomeA.01123-14
PMCID: PMC4214995  PMID: 25359919
4.  Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation 
Differentiation and dedifferentiation of vascular smooth muscle cells (VSMCs) are essential processes of vascular development. VSMC have biosynthetic, proliferative, and contractile roles in the vessel wall. Alterations in the differentiated state of the VSMC play a critical role in the pathogenesis of a variety of cardiovascular diseases, including atherosclerosis, hypertension, and vascular stenosis. This review provides an overview of the current state of knowledge of molecular mechanisms involved in the control of VSMC proliferation, with particular focus on mitochondrial metabolism. Mitochondrial activity can be controlled by regulating mitochondrial dynamics, i.e., mitochondrial fusion and fission, and by regulating mitochondrial calcium handling through the interaction with the endoplasmic reticulum (ER). Alterations in both VSMC proliferation and mitochondrial function can be triggered by dysregulation of mitofusin-2, a small GTPase associated with mitochondrial fusion and mitochondrial–ER interaction. Several lines of evidence highlight the relevance of mitochondrial metabolism in the control of VSMC proliferation, indicating a new area to be explored in the treatment of vascular diseases.
doi:10.3389/fcell.2014.00072
PMCID: PMC4266092  PMID: 25566542
vascular smooth muscle cell; proliferation; mitofusin-2; mitochondrial metabolism; mitochondrial dynamics
5.  Highly Pathogenic Avian Influenza A(H7N3) Virus in Poultry Workers, Mexico, 2012 
Emerging Infectious Diseases  2013;19(9):1531-1534.
We identified 2 poultry workers with conjunctivitis caused by highly pathogenic avian influenza A(H7N3) viruses in Jalisco, Mexico. Genomic and antigenic analyses of 1 isolate indicated relatedness to poultry and wild bird subtype H7N3 viruses from North America. This isolate had a multibasic cleavage site that might have been derived from recombination with host rRNA.
doi:10.3201/eid1909.130087
PMCID: PMC3810917  PMID: 23965808
influenza virus; H7N3; highly pathogenic avian influenza A virus; viruses; conjunctivitis; poultry workers; Mexico
6.  The Genome Sequence of Streptomyces lividans 66 Reveals a Novel tRNA-Dependent Peptide Biosynthetic System within a Metal-Related Genomic Island 
Genome Biology and Evolution  2013;5(6):1165-1175.
The complete genome sequence of the original isolate of the model actinomycete Streptomyces lividans 66, also referred to as 1326, was deciphered after a combination of next-generation sequencing platforms and a hybrid assembly pipeline. Comparative analysis of the genomes of S. lividans 66 and closely related strains, including S. coelicolor M145 and S. lividans TK24, was used to identify strain-specific genes. The genetic diversity identified included a large genomic island with a mosaic structure, present in S. lividans 66 but not in the strain TK24. Sequence analyses showed that this genomic island has an anomalous (G + C) content, suggesting recent acquisition and that it is rich in metal-related genes. Sequences previously linked to a mobile conjugative element, termed plasmid SLP3 and defined here as a 94 kb region, could also be identified within this locus. Transcriptional analysis of the response of S. lividans 66 to copper was used to corroborate a role of this large genomic island, including two SLP3-borne “cryptic” peptide biosynthetic gene clusters, in metal homeostasis. Notably, one of these predicted biosynthetic systems includes an unprecedented nonribosomal peptide synthetase—tRNA-dependent transferase biosynthetic hybrid organization. This observation implies the recruitment of members of the leucyl/phenylalanyl-tRNA-protein transferase family to catalyze peptide bond formation within the biosynthesis of natural products. Thus, the genome sequence of S. lividans 66 not only explains long-standing genetic and phenotypic differences but also opens the door for further in-depth comparative genomic analyses of model Streptomyces strains, as well as for the discovery of novel natural products following genome-mining approaches.
doi:10.1093/gbe/evt082
PMCID: PMC3698927  PMID: 23709624
bacterial next-generation genome sequencing; Streptomyces comparative genomics; copper homeostasis; L/F tRNA transferase; peptide biosynthesis
7.  First Draft Genome Sequence of a Strain from the Genus Citricoccus 
Journal of Bacteriology  2011;193(21):6092-6093.
Bacteria of the genus Citricoccus have been isolated from ecological niches characterized by diverse abiotic stress conditions. Here we report the first genome draft of a strain of the genus Citricoccus isolated from the extremely oligotrophic Churince system in the Cuatro Ciénegas Basin (CCB) in Coahuila, Mexico.
doi:10.1128/JB.06045-11
PMCID: PMC3194908  PMID: 21994924
8.  Systemic Gene Delivery in Large Species for Targeting Spinal Cord, Brain, and Peripheral Tissues for Pediatric Disorders 
Molecular Therapy  2011;19(11):1971-1980.
Adeno-associated virus type 9 (AAV9) is a powerful tool for delivering genes throughout the central nervous system (CNS) following intravenous injection. Preclinical results in pediatric models of spinal muscular atrophy (SMA) and lysosomal storage disorders provide a compelling case for advancing AAV9 to the clinic. An important translational step is to demonstrate efficient CNS targeting in large animals at various ages. In the present study, we tested systemically injected AAV9 in cynomolgus macaques, administered at birth through 3 years of age for targeting CNS and peripheral tissues. We show that AAV9 was efficient at crossing the blood–brain barrier (BBB) at all time points investigated. Transgene expression was detected primarily in glial cells throughout the brain, dorsal root ganglia neurons and motor neurons within the spinal cord, providing confidence for translation to SMA patients. Systemic injection also efficiently targeted skeletal muscle and peripheral organs. To specifically target the CNS, we explored AAV9 delivery to cerebrospinal fluid (CSF). CSF injection efficiently targeted motor neurons, and restricted gene expression to the CNS, providing an alternate delivery route and potentially lower manufacturing requirements for older, larger patients. Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations.
doi:10.1038/mt.2011.157
PMCID: PMC3222525  PMID: 21811247
9.  Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN 
Nature biotechnology  2010;28(3):271-274.
Spinal muscular atrophy (SMA), the most common autosomal recessive neurodegenerative disease affecting children, results in impaired motor neuron function1. Despite knowledge of the pathogenic role of decreased survival motor neuron (SMN) protein levels, efforts to increase SMN have not resulted in a treatment for patients. We recently demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect ~60% of motor neurons when injected intravenously into neonatal mice2–4. Here we use scAAV9-mediated postnatal day 1 vascular gene delivery to replace SMN in SMA pups and rescue motor function, neuromuscular physiology and life span. Treatment on postnatal day 5 results in partial correction, whereas postnatal day 10 treatment has little effect, suggesting a developmental period in which scAAV9 therapy has maximal benefit. Notably, we also show extensive scAAV9-mediated motor neuron transduction after injection into a newborn cynomolgus macaque. This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA.
doi:10.1038/nbt.1610
PMCID: PMC2889698  PMID: 20190738
10.  The influenza A(H1N1) epidemic in Mexico. Lessons learned 
Several influenza pandemics have taken place throughout history and it was assumed that the pandemic would emerge from a new human virus resulting from the adaptation of an avian virus strain. Mexico, since 2003 had developed a National Preparedness and Response Plan for an Influenza Pandemic focused in risk communication, health promotion, healthcare, epidemiological surveillance, strategic stockpile, research and development. This plan was challenged on April 2009, when a new influenza A(H1N1) strain of swine origen was detected in Mexico. The situation faced, the decisions and actions taken, allowed to control the first epidemic wave in the country. This document describes the critical moments faced and explicitly point out the lessons learned focused on the decided support by the government, the National Pandemic Influenza Plan, the coordination among all the government levels, the presence and solidarity of international organizations with timely and daily information, diagnosis and the positive effect on the population following the preventive hygienic measures recommended by the health authorities. The international community will be able to use the Mexican experience in the interest of global health.
doi:10.1186/1478-4505-7-21
PMCID: PMC2765941  PMID: 19785747
11.  The prevalence of chronic diseases and major disease risk factors at different ages among 150 000 men and women living in Mexico City: cross-sectional analyses of a prospective study 
BMC Public Health  2009;9:9.
Background
While most of the global burden from chronic diseases, and especially vascular diseases, is now borne by low and middle-income countries, few large-scale epidemiological studies of chronic diseases in such countries have been performed.
Methods
From 1998–2004, 52 584 men and 106 962 women aged ≥35 years were visited in their homes in Mexico City. Self reported diagnoses of chronic diseases and major disease risk factors were ascertained and physical measurements taken. Age- and sex-specific prevalences and means were analysed.
Results
After about age 50 years, diabetes was extremely common – for example, 23.8% of men and 26.9% of women aged 65–74 reported a diagnosis. By comparison, ischaemic heart disease was reported by 4.8% of men and 3.0% of women aged 65–74, a history of stroke by 2.8% and 2.3%, respectively, and a history of cancer by 1.3% and 2.1%. Cancer history was generally more common among women than men – the excess being largest in middle-age, due to breast and cervical cancer. At older ages, the gap narrowed because of an increasing prevalence of prostate cancer. 51% of men and 25% of women aged 35–54 smoked cigarettes, while 29% of men and 41% of women aged 35–54 were obese (i.e. BMI ≥30 kg/m2). The prevalence of treated hypertension or measured blood pressure ≥140/90 mmHg increased about 50% more steeply with age among women than men, to 66% of women and 58% of men aged 65–74. Physical inactivity was highly prevalent but daily alcohol drinking was relatively uncommon.
Conclusion
Diabetes, obesity and tobacco smoking are highly prevalent among adults living in Mexico City. Long-term follow-up of this and other cohorts will establish the relevance of such factors to the major causes of death and disability in Mexico.
doi:10.1186/1471-2458-9-9
PMCID: PMC2645387  PMID: 19134207
12.  para tu Salud: Reduction of Weight and Waistlines by Integrating Exercise Breaks into Workplace Organizational Routine 
Preventing Chronic Disease  2007;5(1):A12.
Introduction
Proactive worksite strategies that change the physical or sociocultural environment(s) to incorporate obligatory physical activity may be necessary to engage sedentary people. This study describes implementation and evaluation of an intervention, Pausa para tu Salud (Pause for Your Health), that integrated a brief period of group exercise into the workday.
Methods
An uncontrolled pretest–post-test study design tested the effects of integrating daily 10-minute exercise breaks during paid work time during January 2003 through January 2004. A total of 335 Mexican Ministry of Health office workers provided baseline data as a part of routine annual clinical screening examinations.
Results
Baseline mean body mass index and waist circumferences were 27.8 kg/m2 and 87.6 cm for women and 26.6 kg/m2 and 89.7 cm for men. Complete data were available for 271 (80.9%) employees at 1-year follow-up. Two-tailed, paired t-test comparisons were used. Body mass index decreased by 0.32 kg/m2 (P = .05), and waist circumference by 1.6 cm (P = .0009) overall. The body mass index decrease, however, was significant only for men (−0.43 kg/m2, P = .03). Multivariate analyses revealed a significant decrease in diastolic blood pressure among women (z = −2.04, P = .042).
Conclusion
The intervention was associated with significant improvements in both measures of body composition. Substantive health and organizational benefits may result from integrating brief periods of physical activity into the workday if these findings are replicated in randomized controlled trials in other worksites.
PMCID: PMC2248785  PMID: 18082001
13.  HLA haplotypes associated with hemochromatosis mutations in the Spanish population 
BMC Medical Genetics  2004;5:25.
Background
The present study is an analysis of the frequencies of HLA-A and -B antigens and HLA haplotypes in two groups of individuals homozygous for the two main HFE mutations (C282Y and H63D) and a group heterozygous for the S65C mutation.
Methods
The study population includes: 1123 healthy individuals, 100 homozygous for the C282Y mutation, 138 homozygous for the H63D mutation and 17 heterozygous for the S65C mutation. HFE and HLA alleles were detected using DNA-based and microlymphocytotoxicity techniques respectively.
Results
An expected significant association between C282Y and the HLA-A3/B7 haplotype was found, but other HLA haplotypes carrying the -A3 antigen were found: HLA-A3/B62 and HLA-A3/B44. Also, a significant association between H63D mutation and HLA-A29/B44 haplotype was found, and again other HLA haplotypes carrying the HLA-A29 antigen were also found: HLA-A29/B14 and HLA-A29/B62. In addition, the S65C mutation seems to be associated with a HLA haplotype carrying the HLA-A26 antigen.
Conclusion
These findings clearly suggest that HLA-A3/B7 and HLA-A29/B44 are the ancestral haplotypes from which the C282Y and H63D mutations originated, respectively. The frequencies of these mutations in different populations, their geographical distribution, and the degree of the statistical association to the ancestral haplotypes, suggest that the H63D mutation must have occurred earlier than the C282Y mutation.
doi:10.1186/1471-2350-5-25
PMCID: PMC529258  PMID: 15498100
14.  The U.S.-Mexico Border Infectious Disease Surveillance Project: Establishing Binational Border Surveillance 
Emerging Infectious Diseases  2003;9(1):97-102.
In 1997, the Centers for Disease Control and Prevention, the Mexican Secretariat of Health, and border health officials began the development of the Border Infectious Disease Surveillance (BIDS) project, a surveillance system for infectious diseases along the U.S.-Mexico border. During a 3-year period, a binational team implemented an active, sentinel surveillance system for hepatitis and febrile exanthems at 13 clinical sites. The network developed surveillance protocols, trained nine surveillance coordinators, established serologic testing at four Mexican border laboratories, and created agreements for data sharing and notification of selected diseases and outbreaks. BIDS facilitated investigations of dengue fever in Texas-Tamaulipas and measles in California–Baja California. BIDS demonstrates that a binational effort with local, state, and federal participation can create a regional surveillance system that crosses an international border. Reducing administrative, infrastructure, and political barriers to cross-border public health collaboration will enhance the effectiveness of disease prevention projects such as BIDS.
doi:10.3201/eid0901.020047
PMCID: PMC2873746  PMID: 12533288
border health; Mexico; southwestern United States; sentinel surveillance; communicable diseases; hepatitis; viral; human; migrant health; international health; infectious diseases; research

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