Tanzy Love

Gene Expression Patterns During Somatic Embryo Development and Germination in Maize Hi II Callus Cultures

Gene expression patterns were profiled during somatic embryogenesis in a regeneration-proficient maize hybrid line, Hi II, in an effort to identify genes that might be used as developmental markers or targets to optimize regeneration steps for recovering maize plants from tissue culture. Gene expression profiles were generated from embryogenic calli induced to undergo embryo maturation and germination. Over 1,000 genes in the 12,060 element arrays showed significant time variation during somatic embryo development. A substantial number of genes were downregulated during embryo maturation, largely histone and ribosomal protein genes, which may result from a slowdown in cell proliferation and growth during embryo maturation. The expression of these genes dramatically recovered at germination. Other genes up-regulated during embryo maturation included genes encoding hydrolytic enzymes (nucleases, glucosidases and proteases) and a few storage genes (an α-zein and caleosin), which are good candidates for developmental marker genes. Germination is accompanied by the up-regulation of a number of stress response and membrane transporter genes, and, as expected, greening is associated with the up-regulation of many genes encoding photosynthetic and chloroplast components. Thus, some, but not all genes typically associated with zygotic embryogenesis are significantly up or down-regulated during somatic embryogenesis in Hi II maize line regeneration. Although many genes varied in expression throughout somatic embryo development in this study, no statistically significant gene expression changes were detected between total embryogenic callus and callus enriched for transition stage somatic embryos.

Prenatal exposure to methyl mercury from fish consumption and polyunsaturated fatty acids: associations with child development at 20 mo of age in an observational study in the Republic of Seychelles

BACKGROUND Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs) but also contains the neurotoxicant methyl mercury (MeHg). PUFAs may modify the relation between prenatal MeHg exposure and child development either directly by enhancing neurodevelopment or indirectly through the inflammatory milieu. OBJECTIVE The objective was to investigate the associations of prenatal MeHg exposure and maternal PUFA status with child development at 20 mo of age. DESIGN The Seychelles Child Development Study Nutrition Cohort 2 is an observational study in the Republic of Seychelles, a high-fish-eating population. Mothers were enrolled during pregnancy and their children evaluated at 20 mo of age by using the Bayley Scales of Infant Development II (BSID-II), the MacArthur Bates Communicative Development Inventories (CDI), and the Infant Behavior Questionnaire-Revised. There were 1265 mother-child pairs with complete data. RESULTS Prenatal MeHg exposure had no direct associations with neurodevelopmental outcomes. Significant interactions were found between MeHg and PUFAs on the Psychomotor Developmental Index (PDI) of the BSID-II. Increasing MeHg was associated with lower PDI but only in children of mothers with higher n-6/n-3. Among mothers with higher n-3 PUFAs, increasing MeHg was associated with improved PDI. Higher maternal docosahexaenoic acid (DHA) was associated with improved CDI total gestures (language development) but was significantly adversely associated with the Mental Development Index (MDI), both with and without MeHg adjustment. Higher n-6:n-3 ratios were associated with poorer scores on all 3 CDI outcomes. CONCLUSIONS We found no overall adverse association between prenatal MeHg exposure and neurodevelopmental outcomes. However, maternal PUFA status as a putative marker of the inflammatory milieu appeared to modify the associations of prenatal MeHg exposure with the PDI. Increasing DHA status was positively associated with language development yet negatively associated with the MDI. These findings may indicate the existence of an optimal DHA balance with respect to arachidonic acid for different aspects of neurodevelopment.

Designing a genome-based HIV incidence assay with high sensitivity and specificity.

Objective:Considerable inaccuracy in estimates of HIV incidence has been a serious obstacle to the development of efficient HIV/AIDS prevention and interventions. Accurately distinguishing recent or incident infections from chronic infections enables one to monitor epidemics and evaluate the impact of HIV prevention/intervention trials. However, serological testing has not been able to realize these promises due to a number of critical limitations. Our study is to design a novel scheme of identifying incident infections in a highly accurate manner, based on the characteristics of HIV gene diversification within an infected individual. Methods:We perform a comprehensive meta-analysis on 5596 full envelope HIV genes generated by single genome amplification-direct sequencing from 182 incident and 43 chronic cases. We devise a binary classification test based on the tail characteristics of the Hamming distance distribution of sequences. Results:We identify a clear signature of incident infections, the presence of closely related strains in the sampled HIV envelope gene sequences in each HIV-infected patient, in both single-variant and multivariant transmissions. The sequence similarity used as a biomarker is found to have high specificity and sensitivity, greater than 95%, and is robust to viral and host-specific factors such as the clade of the viral strain, viral load, and the length and location of sequences in the HIV envelope gene. Conclusion:Because of rapid and continuing improvements in sequencing technology and cost, sequence-based incidence assays hold great promise as a means of quantifying HIV incidence from a single blood test.

Autism Spectrum Disorder Phenotypes and Prenatal Exposure to Methylmercury

Background: There continues to be public concern that mercury exposure and autism spectrum disorder (ASD) may be associated. The primary source of exposure to organic mercury in humans is to methylmercury from fish consumption. We evaluated the association between prenatal methylmercury exposure and ASD phenotype in children and adolescents in the Republic of Seychelles, where fish consumption is high. Methods: We administered the Social Communication Questionnaire to parents of a cohort of 1784 children, adolescents, and young adults. The Social Responsiveness Scale was administered to teachers of 537 cohort subjects at about 10 years of age. Prenatal exposure to methylmercury was measured in maternal hair samples collected at or near the time of birth. Multivariable regression models evaluated the relationship between prenatal methylmercury exposure and ASD phenotypic scores, adjusting for relevant covariates. Results: The mean prenatal methylmercury exposure for subjects in the analysis was 8.4 ppm (standard deviation [SD] = 5.7). The mean Social Communication Questionnaire score was 8.0 (SD = 4.4). The mean prenatal methylmercury exposure for subjects with Social Responsiveness Scale scores was 6.7 ppm (SD = 4.4) and the mean Social Responsiveness Scale score was 57.6 (SD = 26.8). No consistent association between prenatal methylmercury exposure and ASD screening instrument was found, using linear and nonlinear regression analyses. Conclusions: Prenatal exposure to methylmercury was not associated with ASD phenotypic behaviors in our cohort of high fish consumers. Our findings contribute to the growing literature suggesting that exposure to methylmercury does not play an important role in the development of ASD phenotypic behavior.

Mathematical Modeling of Ultradeep Sequencing Data Reveals that Acute CD8+ T-Lymphocyte Responses Exert Strong Selective Pressure in Simian Immunodeficiency Virus-Infected Macaques but Still Fail To Clear Founder Epitope Sequences

ABSTRACT The prominent role of antiviral cytotoxic CD8+ T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef103-111RM9 (RM9), Tat28-35SL8 (SL8), and Gag181-189CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day−1 within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day−1 within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

Growth hormone benefits children with 18q deletions

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long‐term outcomes for the treated individuals.

Reconceptualizing the classification of PNAS articles.

PNAS article classification is rooted in long-standing disciplinary divisions that do not necessarily reflect the structure of modern scientific research. We reevaluate that structure using latent pattern models from statistical machine learning, also known as mixed-membership models, that identify semantic structure in co-occurrence of words in the abstracts and references. Our findings suggest that the latent dimensionality of patterns underlying PNAS research articles in the Biological Sciences is only slightly larger than the number of categories currently in use, but it differs substantially in the content of the categories. Further, the number of articles that are listed under multiple categories is only a small fraction of what it should be. These findings together with the sensitivity analyses suggest ways to reconceptualize the organization of papers published in PNAS.

Prenatal exposure to dental amalgam in the Seychelles Child Development Nutrition Study: associations with neurodevelopmental outcomes at 9 and 30 months.

BACKGROUND Dental amalgam is approximately 50% metallic mercury and releases mercury vapor into the oral cavity, where it is inhaled and absorbed. Maternal amalgams expose the developing fetus to mercury vapor. Mercury vapor can be toxic, but uncertainty remains whether prenatal amalgam exposure is associated with neurodevelopmental consequences in offspring. OBJECTIVE To determine if prenatal mercury vapor exposure from maternal dental amalgam is associated with adverse effects to cognition and development in children. METHODS We prospectively determined dental amalgam status in a cohort of 300 pregnant women recruited in 2001 in the Republic of Seychelles to study the risks and benefits of fish consumption. The primary exposure measure was maternal amalgam surfaces present during gestation. Maternal occlusal points were a secondary measure. Outcomes were the childs mental (MDI) and psychomotor (PDI) developmental indices of the Bayley Scales of Infant Development-II (BSID-II) administered at 9 and 30 months. Complete exposure, outcome, and covariate data were available on a subset of 242 mother-child pairs. RESULTS The number of amalgam surfaces was not significantly (p>0.05) associated with either PDI or MDI scores. Similarly, secondary analysis with occlusal points showed no effect on the PDI or MDI scores for boys and girls combined. However, secondary analysis of the 9-month MDI was suggestive of an adverse association present only in girls. CONCLUSION We found no evidence of an association between our primary exposure metric, amalgam surfaces, and neurodevelopmental endpoints. Secondary analyses using occlusal points supported these findings, but suggested the possibility of an adverse association with the MDI for girls at 9 months. Given the continued widespread use of dental amalgam, we believe additional prospective studies to clarify this issue are a priority.

Neurodevelopmental outcomes at 5 years in children exposed prenatally to maternal dental amalgam: the Seychelles Child Development Nutrition Study.

Limited human data are available to assess the association between prenatal mercury vapor (Hg⁰)) exposure from maternal dental amalgam restorations and neurodevelopment of children. We evaluated the association between maternal dental amalgam status during gestation and childrens neurodevelopmental outcomes at 5 years in the Seychelles Child Development Nutrition Study (SCDNS). Maternal amalgam status was determined prospectively in a longitudinal cohort study examining the associations of prenatal exposure to nutrients and methylmercury (MeHg) with neurodevelopment. A total of 236 mother-child pairs initially enrolled in the SCDNS in 2001 were eligible to participate. Maternal amalgam status was measured as number of amalgam surfaces (the primary metric) and number of occlusal points. The neurodevelopmental assessment battery was comprised of age-appropriate tests of cognitive, language, and perceptual functions, and scholastic achievement. Linear regression analysis controlled for MeHg exposure, maternal fatty acid status, and other covariates relevant to child development. Maternal amalgam status evaluation yielded an average of 7.0 surfaces (range 0-28) and 11.0 occlusal points (range 0-40) during pregnancy. Neither the number of maternal amalgam surfaces nor occlusal points were associated with any outcome. Our findings do not provide evidence to support a relationship between prenatal exposure to Hg⁰ from maternal dental amalgam and neurodevelopmental outcomes in children at 5 years of age.

Methyl mercury exposure and neurodevelopmental outcomes in the Seychelles Child Development Study Main cohort at age 22 and 24years.

BACKGROUND All fish contain methyl mercury (MeHg), a known neurotoxicant at adequate dosage. There is still substantial scientific uncertainty about the consequences, if any, of mothers consuming fish with naturally-acquired levels of MeHg contamination. In 1989-1990, we recruited the Main Cohort of the Seychelles Child Development Study to assess the potential developmental effects of prenatal MeHg exposure. We report here on associations with neurodevelopmental outcomes obtained at 22 and 24years of age. METHODS Neurodevelopmental tests at 22years included the Boston Naming Test, Cambridge Neuropsychological Test Automated Battery (CANTAB), and the Profile of Mood States. At 24years, we administered the Stroop Word-Color Test, the Barkley Adult ADHD Rating Scale, the Test of Variables of Attention, and the Finger Tapping test. We also administered a healthy behaviors survey at both ages. Primary analyses examined covariate-adjusted associations in multiple linear regression models with prenatal MeHg exposure. In secondary analyses we also examined associations with recent postnatal MeHg exposure. RESULTS We did not observe adverse associations between prenatal MeHg exposure and any of the measured endpoints. Some measures of attention, executive function, and delayed recall showed improved performance with increasing exposure. Secondary analysis did not show consistent patterns of association with postnatal exposure. CONCLUSIONS Our cohort has been examined at ten different ages over 24years of follow-up. Findings suggest that prenatal and recent postnatal MeHg exposure from ocean fish consumption is not adversely associated with neurobehavioral development at levels that are about ten times higher than typical U.S. exposures.