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Projects in Chile

Spatial Memory performance  in forme Iron deficiency  anemia during  adolescencia and early adulthood

University of Michigan investigator(s) and unit:  Jorge Delva, Phd., Center for Human Growth and Development; School of Social Work

International colleague(s) name and unit: Dr. Cecilia Algarin. Human Nutrition Unit, Institute of Nutrition and Food Technology (INTA), University of Chile 

Purpose: To investigate the Spatial Memory performance in former Iron deficiency anemic subjects when they were 16ys old and 22 y old.

 Rationale: Iron deficiency anemia in infancy alters different cognitive functions though different mechanisms as myelin, dopamine and energetic neuronal dysfunction.

Study design and methods:

The sample belongs to a follow up study initiated in 1990. A sub-sample from this study former Iron deficiency anemia and controls were assessed at 16 and 22 years with a virtual water maze test to evaluate the spatial memory capacity. 

Anticipated undergraduate/graduate st1udent activities on project:

  1. To organize the results already obtained from the water maze test.
  2. To analyze the data and obtain the results.
  3. To run statistical analysis and compare the groups.

Techniques/methods students should become familiar with in advance:

The student should have computation skills and statistical analyzes experience. 

Suggested readings (minimum of 3-5 articles): all articles are available for interested students. 

  1. Algarin C. et al. 2013. Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. DEDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY. DOI: 10.1111/dmcn.12118
  2. Congdon E.L.2016 Iron Deficiency in Infancy is Associated with Altered Neural Correlates of Recognition Memory at 10 Years. The Journal of Pediatrics. Article in press.
  3. Algarin C., et.al. 2003. Iron Deficiency Anemia in Infancy: Long-Lasting Effects on Auditory and Visual System Functioning. The International Pediatric Foundation, Vol. 53, No. 2
  4. Nadel L, et.al. Human Place Learning in a Computer Generated Arena1 (Chapter in a book. It would be send to interested students)

    Biopyschosocial Determinants of Cardiovascular Risk in Adolescence and Young Adulthood

University of Michigan investigator(s) and unit: Jorge Delva, Phd., Center for Human Growth and Development; School of Social Work

International colleague(s) name and unit: Raquel Burrows M.D., Paulina Correa Ph.D., Estela Blanco M.P.H. 

Purpose: Design and implement an analysis project using data from previous waves of data collection (infancy-22 years).  

Rationale: To study the association of Adolescents with good academic performance are less likely to report unhealthy behaviours, including alcohol, tobacco and drug consumption, physical inactivity and risky sex

Study design and methods: This project aims to understand biological and psychosocial risks and circadian patterns on the development of obesity and metabolic risks in a cohort of Chilean adolescents.

This proposal involves 1100 Chilean young adults, assessed in infancy, 5, 10, 16 years and is currently being evaluated at 21 and 22 years as part of a NIH-supported cohort study that began as iron deficiency anemia preventive trial in infancy (n=1645). Detailed longitudinal data related to growth, health and development have been collected. At 16 to 17 years, the youth participated in study of activity, sleep and eating patterns using actigraphic recording and laboratory assessment of eating behavior. In addition, we measured anthropometry, fat and muscle mass (DXA), fasting glucose, insulin (HOMA IR), lipids, leptin, ghrelin, adiponectin, orexin, CRP, and TNF-α. Detailed information about family history, alcohol, cannabis and tobacco, health, and psychosocial functioning was also collected. Young adult (age 22-23) follow-up is currently underway (data collection began in May 2015) and also includes: 24h dietary recall, an assessment of eating behavior questionnaire, a liver ultrasound for fatty liver disease detection, and a modified version of the eating in the absence of hunger paradigm. Data on academic attainment and current labor status is also available for the full sample. Last, for a subset of participants having children we have anthropometric and breastfeeding information of their children’s.

Anticipated undergraduate/graduate student activities on project:

Topics 1 to 4 led by Raquel Burrows

  • Influence of early nutrition and growth in cardiovascular and metabolic risk of emerging adulthood
  • Biological and environmental factors of adolescence and their association with increased risk of metabolic syndrome in early adulthood.
  • Substance abuse in adolescence and its association with cardiometabolic risk in early adulthood.
  • Non-alcoholic fatty liver disease in emerging adulthood and its association with diet and physical activity in adolescence

Topics 5 & 6 led by Paulina Correa

  • The relationship of healthful living with graduation/drop-out rates in high school, application for higher education and job status.
  • Substance abuse in adolescence and its association with educational outcomes in the transition from secondary to higher education.

Topics 7 & 8 led by Estela Blanco

7)  Biological and environmental factors related to gain in bone mass between adolescence and emerging adulthood

8)  Lifestyles of participants in a cohort and nutrition and growth on the offspring 

Techniques/methods students should become familiar with in advance:

Data analysis experience (Introduction to intermediate level) 

Suggested readings (minimum of 3-5 articles):

Gahagan S. Development of eating behavior: biology and context. J Dev Behav Pediatr. 2012 Apr; 33(3):261-71. Review Article. PMID: 22472944.

Khuc K, Blanco E, Burrows R, Reyes M, Castillo M, Lozoff B, Gahagan S. Adolescent metabolic syndrome risk is increased with higher infancy weight gain and decreased with longer breast feeding. Int J Pediatr. 2012;2012:478610.

Kang Sim DE, Cappiello M, Castillo M, Lozoff B, Martinez S, Blanco E, Gahagan S. Postnatal growth patterns in a Chilean cohort: the role of SES and family environment.  Int J Pediatr, 2012;2012:354060.

Gahagan S, Yu S, Kaciroti N, Castillo M, Lozoff B. Linear and Ponderal Growth Trajectories in Well-Nourished, Iron-Sufficient Infants Are Unimpaired by Iron Supplementation. Journal of Nutrition 139(11):2106-12, 2009. PMID: 19776186.

Burrows R, Correa P, Reyes M, Blanco E, Albala C, S. Gahagan.  Healthy Chilean adolescents with HOMA-IR ≥ 2.6 have increased cardio-metabolic risk:  Association with genetic, biological and environmental factors.  J Diab Res 2015. Article ID 783296

Burrows R, Correa P, Reyes M, Blanco E, Albala C, S. Gahagan. High cardiometabolic risk in healthy Chilean adolescents: Association with anthropometric, biological and life style factors. Public Health Nutrition, 2015; Doi.org/10.1017/S136898001500158

Gahagan et al. Developmental Origins of Pediatric Obesity. Int J Pediatr 2012;Volume 2012, Article ID 309863, 3 pages.

Blanco E, Reyes M, Burrows R , Martinez SM  and Gahagan S. Low bone mineral density in a cohort of normal, overweight and obese  Chilean adolescents. J Clin Nursing 2011;20:3577-3579.

Correa P, Burrows R, Ibaceta C, Orellana Y, Ivanovic D. Physically active Chilean school kids perform better in language and mathematics. Health Promot Intl 2014: doi: 10.1093/heapro/dau010

Burrows R, Correa P, Orellana Y, Almagliá A, Lizana P, Ivanovic D. Scheduled Physical Activity Is Associated With Better Academic Performance In Chilean School-Age Children. J Phys Activi Health, 2014, 11, 1600 -1606, doi: /10.1123/jpah.2013-0125.

Correa-Burrows P, Burrows R, Orellana Y, Ivanovic D. The relationship between unhealthy snacking at school and academic outcomes: A population study in Chilean school children. Public Health Nutrition, 2015, 18(11):2022-30. doi: 10.1017/S1368980014002602

Correa-Burrows P, Blanco E, Reyes M, Castillo M, Peirano P, Algarín C, Lozoff B, Gahagan S, Burrows R. Leptin status in adolescence is associated with academic performance in high school: a cross-sectional study in a Chilean birth cohort. BMJ Open. 2016 Oct 18;6(10):e010972. doi: 10.1136/bmjopen-2015-010972. 

Humanization of zebrafish (Danio rerio) to study the human gut microbiome

University of Michigan investigator(s) and unit: Jorge Delva, Phd., Center for Human Growth and Development; School of Social Work

International colleague(s) name and unit: Paola Navarrete, PhD, Assistant Professor, Laboratory of Microbiology and Probiotics, INTA, University of Chile. 

Summary

Human intestinal microbiota is constituted by a complex microbial ecosystem, mostly composed by anaerobic and oxygen sensitive bacteria. The role of these microorganisms in health and disease has not yet been fully described, in part due to the difficulty to grow these bacteria and the lack of simple biological models. In this regard, we propose the zebrafish (Danio rerio), which has been successfully used as a model of human pathogen infection, for the study of the human gut microbiota-host interactions. To date, only one study has colonized zebrafish larvae with two strains from the human gut microbiota. It has been reported that the establishment of a stable anaerobic microbiota involves different factors including i) the replacement of aerotolerant bacteria (early colonizers) by anaerobic microorganisms, ii) cross-feeding process, iii) nutrient availability in the gut habitat, iv) host selection, v) bacterial-related factors, among others. In this study we want to evaluate some bacterial factors involved in the colonization process of human anaerobic gut bacteria in the zebrafish gut. 

Suggested readings (minimum of 3-5 articles):

  1. Bates, J.M., et al. (2006). Dev Biol 297(2): 374-386.
  2. Bates, J.M., et al. (2007). Cell Host Microbe 2(6): 371-382.
  3. Browne HP, et al. (2016) Nature. 533(7604): 543-546. 12
  4. Caruffo M, et al. (2015). Front Microbiol. 7;6:1093. doi: 10.3389/fmicb.2015.01093.
  5. Caruffo M, et al. (2016). Front Cell Infect Microbiol. http://dx.doi.org/10.3389/fcimb.2016.00127
  6. DeLong, E. (2014). Cell. 159(2):233-5. doi: 10.1016/j.cell.2014.09.043.
  7. El Aidy S, et al. (2013). ISME J 7: 743–55.
  8. El Aidy S et al. (2013) Bioessays. 35(10): 913-23.
  9. Gootenberg and Turnbaugh. (2011) J Anim Sci. 89(5):1531-7. doi: 10.2527/jas.2010-3371.
  10. Rawls, J.F., et al. (2006). Cell 127(2): 423-433.
  11. Toh, M.C., et al. (2013) Zebrafish 10(2): 194-198.
  12. Seedorf, H. et al. (2014). Cell 159(2): 253–266. doi:10.1016/j.cell.2014.09.008.

    Virulence genes expression of Listeria monocytogenes strain in response to exposure at bioactive compounds

University of Michigan investigator(s) and unit: Jorge Delva, Phd., Center for Human Growth and Development; School of Social Work

International colleague(s) name and unit: Angélica Reyes-Jara PhD., Assistant Professor, Laboratory of Microbiology and Probiotics. INTA, University of Chile.

Purpose: To evaluate the expression level of genes related to virulence the L. monocytogenes in response to different stress conditions 

Rationale:Foodborne pathogens are a growing worldwide which is a concern for human diseases and public health. One of these pathogenic microorganisms is Listeria monocytogenes, which can resist various important barriers applied through the food chain production, such as refrigeration temperatures. L. monocytogenes causes listeriosis, a disease that may be severe, with high mortality, and that affect mainly newborns, pregnant women, elderly, and patients whose immunity is compromised.

The adaptive responses associated with environmental stress are critical to bacterial survival. Bacteria can exhibit high levels of resistance to one or more environmental stresses such as temperature, osmolarity, metals, radiation, pH, starvation, as well as resistance to noxious chemicals and antibiotics. Several sensing mechanisms are involved in the maintenance of the balance, where the sensors convert the input signals into regulatory outputs, usually at the level of transcription, which allows the bacterium survive and adapt to new environment and maintain its homeostasis (Hobman et al., 2007).

Antimicrobial strategies to overcome the persistence of L. monocytogenes in food industry are essential. Bioactive compound as polyphenolic compounds have showed potential to inhibit L. monocytogenes (Apostolitis et al, 2008), however it is not known what is the effect of these compounds over gene expression in L. monocytogenes, in special virulence related genes and other genes related to L. monocytogenes survival (as biofilm related genes).

The aim of this project is to evaluate the expression level of genes virulence-related of L. monocytogenes in response to exposure at bioactive compounds.

We will be very pleased to receive in our lab a student from the Minority International Research Training Program of The Fogarty International Center and The Office of Research on Minority Health (NIH) to be trained in the determination of transcriptional response to bioactive compounds of L. monocytogenes a foodborne microorganism.

Techniques/methods students should become familiar with in advance:

  • To identify the presence of virulence-related genes (Hadjilouka et al 2016 and Lebreton et al 2016) in monocytogenes strains isolated from different food matrix: Will be design PCR primers and performed PCR for the following genes: prfA, hly plcA, plcB, sigB, inlA, inlB, inlC, inlJ, virR, virS, codY, lmo2672 and lmo2470
  • To evaluate gene expression for select virulence-related genes reported previously. The gene expression level will be measured by qPCR under the exposure of L. monocytogenes strains to bioactive compounds (as like as polyphenolic compounds). The techniques include bacterial culture, RNA extraction and cDNA synthesis. 

Suggested readings (minimum of 3-5 articles):

  • Ferreira V, Wiedmann M, Teixeira P, Stasiewicz MJ. 2014. Listeria monocytogenes persistence in food-associated environments: epidemiology, strain characteristics, and implications for public health. J Food Prot, 77(1):150-170
  • Montero D, Bodero M, Riveros G, Lapierre L, Gaggero A, Vidal RM, Vidal M. 2015. Molecular epidemiology and genetic diversity of Listeria monocytogenes isolates from a wide variety of ready-to-eat foods and their relationship to clinical strains from listeriosis outbreaks in Chile. Front Microbiol. 30;6:384. doi: 10.3389/fmicb.2015.00384.
  • Apostolidis E, Kwon YI, Shetty K. 2008. Inhibition of Listeria monocytogenes by oregano, cranberry and sodium lactate combination in broth and cooked ground beef systems and likely mode of action through proline metabolism. Int J Food Microbiol. 10;128(2):317-24. doi: 10.1016/j.ijfoodmicro.2008.09.012.
  • Cordero N, Maza F, Navea-Perez H, Aravena A, Marquez-Fontt B, Navarrete P, Figueroa G, González M, Latorre M, Reyes-Jara A. 2016. Different Transcriptional Responses from Slow and Fast Growth Rate Strains of Listeria monocytogenes Adapted to Low Temperature. Front Microbiol. 1;7:229. doi: 10.3389/fmicb.2016.00229.
  • Hadjilouka A, et al. 2016. Expression of Listeria monocytogenes key virulence genes during growth in liquid medium, on rocket and melon at 4, 10 and 30 °C. Food Microbiol 2016, 55:7-15.
  • Lebreton A, Cossart P. 2016. RNA- and protein-mediated control of Listeria monocytogenes virulence gene expression. RNA Biol 1-11 

Simple Sugar Metabolism during peach and sweet cherry fruit ripening

University of Michigan investigator(s) and unit: Jorge Delva, Phd., Center for Human Growth and Development; School of Social Work

International colleague(s) and unit: Dr Lee Meisel, Plant Molecular Genetics Laboratory, Basic Nutrition Unit, INTA, University of Chile

Purpose: Identify the underlying genomic factors that regulate simple sugar metabolism in peaches and sweet cherries

Rationale:In the mist of global climate change, the world will be faced with the challenge of ensuring both food and nutritional security.   Fruits and vegetables, the richest natural sources of micronutrients, are vital to ensuring nutritional security.  Within, the past decade, the International Rosaceae community has worked together in order to develop genomic and breeding tools towards better understanding and improving the vast diversity of fruits in the Rosaceae family.  This family consists of over 100 genera and 3,000 species that include many important fruit, nut, ornamental and wood crops including: almonds, apricots, pears, plum, raspberry, sweet cherry, sour cherry and strawberry.   These internationally coordinated efforts have yielded the complete genome sequences of a handful of Rosaceae species including apple, woodland strawberry, peach, plum as well as Asian and European pear.

There is a large nutritional diversity among different fruit species within the Rosaceae family.  The conserved synteny among these family members may be used to begin to decipher the underlining genetic variability that leads to nutritional diversity of these species.  Furthermore, the nutritional value in fruits varies during the fruit ripening process, such as the content of simple sugars.  The objective of this project is to decipher the metabolic pathway for simple sugars during peach and sweet cherry fruit ripening.

Study design and methods: 

Utilizing information for the peach and sweet cherry genomes as well as available RNA-seq data, the students will reconstruct simple sugar metabolism during fruit ripening, in sweet cherries and peaches.  Gene expression analysis of key regulatory genes involved in simple sugar metabolism will be performed by analyzing RNA-seq data as well as performing qPCR analysis.

Anticipated undergraduate/graduate student activities on project:

–    In silco reconstruction of sugar metabolism in peaches or sweet cherries, using bioinformatic strategies and software such as CLC Genomics Workbench.

–    Mine RNA-seq data for differential expression of key regulatory enzymes during fruit ripening and confirmation of differential expression using qPCR analyses.

Techniques/methods students should become familiar with in advance:

Basic knowledge about Molecular biology and molecular biology techniques (PCR, blast analyses)

Suggested readings (minimum of 3-5 articles):

  1. Seymour et al (2013)  Fruit development and ripening.  Annu. Rev. Plant Biol 64:219-241
  2. Martin et al (2013) Plants, Diet and Health.  Annu Rev Plant Biol.  64:19-46.
  3. Martin (2013)  The interface between plant metabolic engineering and human health.  Current Opinion in Biotechnology.  24:344-353.
  4. Shulaev et al (2008) Multiple Models for Rosaceae Genomics Plant Physiology 147:985-1003.
  5. Koepke et al (2013) Comparative genomic analyses in Prunoideae to identify biologically relevant polymorphisms.  Plant Biotec J 11:883-893.
  6. Jung and Main (2014) Genomics and bioinformatics resources for translational science in Rosaceae.  Plant Biotechnol Rep 8:49-64.