Effects of Contingent Maternal Imitation vs. Contingent Motherese Speech on Infant Canonical Babbling

Maternal vocal stimulation plays a vital role in infants’ language acquisition. Contingent maternal imitation and contingent motherese speech were used in an alternating sequence as reinforcers to a 12 month-old infant’s canonical babbling. Both vocal contingencies function as reinforcers; however, motherese speech produced the highest frequency of canonical babbling.

The effects of paternal and maternal nurturance and involvement on young adult academic outcomes

The present study examines how mothering and fathering impact child academic outcomes in divorced and intact families, and if there are unique influences of mothering and fathering variables for sons and daughters. An ethnically diverse sample of 1,714 university students from Florida International University (n=1371) and Florida State University (n=343) responded to measures on a questionnaire that included the Nurturant Fathering and Mothering Scales (Finley & Schwartz, 2004; Schwartz & Finley, 2005; Finley & Schwartz, 2006), the Mother and Father Involvement Scales (Finley, Mira, & Schwartz, 2008), demographic measures, and academic outcome measures. In intact families, mothering and fathering variables were significantly correlated with each other, and positively correlated with child academic outcomes including grades, GPA, academic satisfaction, and academic importance. In divorced families, mothering and fathering variables were not correlated with each other. Furthermore, when analyzing divorced families, significant effects were found for both parent and child gender. Mothering variables were found to have the greatest positive impact for sons' academic outcomes. Maternal nurturance and maternal involvement were correlated positively with academic outcomes for sons from divorced families and accounted for 3-4% of the unique variance explained. Consistently, desired mother involvement, how much involvement the child wished they had received, was negatively correlated with academic outcomes for sons from divorced families and accounted for 10-15% of the unique variance explained. This means that when the amount of maternal involvement that sons in divorced families received matched or exceeded their desired level of involvement, sons had more positive academic outcomes including grades, GPA, satisfaction with academics and academic importance. This suggests that in intact family forms, nurturant and involved mothering and fathering have a positive effect on academic outcomes for sons and daughters. In divorced family forms, the effects of fathering on child academic outcomes were not significant. Therefore, in divorced families, the positive effects fathering on academic outcomes of sons and daughters drop out, and mothers are uniquely important for sons' academic success.^

The use of quantitative polymerase chain reaction amplification method to determine sex ratio of human spermatozoa in semen and to determine maternal contamination of amniotic fluid samples

We have modified a technique which uses a single pair of primer sets directed against homologous but distinct genes on the X and Y chromosomes, all of which are coamplified in the same reaction tube with trace amounts of radioactivity. The resulting bands are equal in length, yet distinguishable by restriction enzyme sites generating two independent bands, a 364 bp X-specific band and a 280 bp Y-specific band. A standard curve was generated to show the linear relationship between X/Y ratio average vs. %Y or %X chromosomal content. Of the 51 purified amniocyte DNA samples analyzed, 16 samples showed evidence of high % X contamination while 2 samples demonstrated higher % Y than the expected 50% X and 50% Y chromosomal content. With regards to the 25 processed sperm samples analyzed, X-sperm enrichment was evident when compared to the primary sex ratio whereas Y-sperm was enriched when we compared before and after selection samples.

Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation

Acknowledgements Research was funded by the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE). The authors have no conflicts of interest to declare.

Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation

Acknowledgements Research was funded by the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE). The authors have no conflicts of interest to declare.

Maternal gestational weight gain and offspring's risk of cardiovascular disease and mortality

Funding: This research was supported by Chest Heart and Stroke Scotland (R10/A128)

Basement-cover tectonics, structural inheritance and deformation migration in the outer parts of orogenic belts : A view from the western Alps

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Maternal gestational weight gain and offspring's risk of cardiovascular disease and mortality

Funding: This research was supported by Chest Heart and Stroke Scotland (R10/A128)

Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation

Acknowledgements Research was funded by the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE). The authors have no conflicts of interest to declare.

Maternal HIV-1 envelope-specific antibody responses and reduced risk of perinatal transmission.

Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1-transmitting mothers and 165 propensity score-matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1-infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3-specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.

Dissecting the Functional Impacts of Non-Coding Genetic Variation

A large proportion of the variation in traits between individuals can be attributed to variation in the nucleotide sequence of the genome. The most commonly studied traits in human genetics are related to disease and disease susceptibility. Although scientists have identified genetic causes for over 4,000 monogenic diseases, the underlying mechanisms of many highly prevalent multifactorial inheritance disorders such as diabetes, obesity, and cardiovascular disease remain largely unknown. Identifying genetic mechanisms for complex traits has been challenging because most of the variants are located outside of protein-coding regions, and determining the effects of such non-coding variants remains difficult. In this dissertation, I evaluate the hypothesis that such non-coding variants contribute to human traits and diseases by altering the regulation of genes rather than the sequence of those genes. I will specifically focus on studies to determine the functional impacts of genetic variation associated with two related complex traits: gestational hyperglycemia and fetal adiposity. At the genomic locus associated with maternal hyperglycemia, we found that genetic variation in regulatory elements altered the expression of the HKDC1 gene. Furthermore, we demonstrated that HKDC1 phosphorylates glucose in vitro and in vivo, thus demonstrating that HKDC1 is a fifth human hexokinase gene. At the fetal-adiposity associated locus, we identified variants that likely alter VEPH1 expression in preadipocytes during differentiation. To make such studies of regulatory variation high-throughput and routine, we developed POP-STARR, a novel high throughput reporter assay that can empirically measure the effects of regulatory variants directly from patient DNA. By combining targeted genome capture technologies with STARR-seq, we assayed thousands of haplotypes from 760 individuals in a single experiment. We subsequently used POP-STARR to identify three key features of regulatory variants: that regulatory variants typically have weak effects on gene expression; that the effects of regulatory variants are often coordinated with respect to disease-risk, suggesting a general mechanism by which the weak effects can together have phenotypic impact; and that nucleotide transversions have larger impacts on enhancer activity than transitions. Together, the findings presented here demonstrate successful strategies for determining the regulatory mechanisms underlying genetic associations with human traits and diseases, and value of doing so for driving novel biological discovery.

Information Interventions to Reduce Maternal Mortality in Indonesia

Indonesia consistently records higher levels of maternal mortality than other countries in Southeast Asia with its same level of socioeconomic development. I use a quasi-experimental, difference-in-differences approach to understand whether the role of information on the risk of death in childbirth can change women’s reproductive behaviors. In the first two chapters, I use the Maternal Mortality Module from the Demographic and Health Survey (DHS) in Indonesia to examine fertility and reproductive behavior responses to a sister’s death in childbirth. Fertility desires remain relatively unchanged but women take up behaviors in subsequent births that avert the risk of maternal death. In the last chapter, I combine population-representative data from the DHS with a village-level census (PODES) on service availability to understand how a village-level intervention to improve obstetric service use using a birth preparedness and complications readiness (BPCR) approach may improve obstetric service use. In this study, I find that the Desa Siaga intervention in Indonesia improved knowledge of the danger signs of complications among women but not among men relative to villages that did not get the program while controlling for endogenous program placement. More women got antenatal care due to the program but use of a skilled birth attendant and postpartum care did not change as a result of the intervention. Both genders report discussing a blood donor in preparation for delivery.

Post-cesarean Section Peritonitis at a Referral Hospital in Rwanda: Factors Associated with Maternal Morbidity and Mortality

Background: Post-cesarean section peritonitis is the leading cause of maternal morbidity and mortality at the main referral hospital in Rwanda. Published data on the management of post-cesarean section peritonitis is limited. This study examined predictors of maternal morbidity and mortality for post-cesarean peritonitis.

Methods: We performed a prospective observational cohort study at the University Teaching Hospital Kigali (CHUK) from January 1 until December 31 2015, followed by a retrospective chart review of all subjects with post-cesarean section peritonitis admitted to CHUK from January 1 until December 31, 2014. All patients admitted with the diagnosis of post-cesarean section peritonitis undergoing exploratory laparotomy at CHUK were enrolled. Patients were followed to either discharge or death. Study variables included baseline demographic/clinical characteristics, admission physical exam, intraoperative findings, and management. Data were analyzed using STATA version 14.

Results: Of the 167 patients enrolled, 81 survived without requiring hysterectomy (49%), 49 survived requiring hysterectomy (29%), and 36 died (22%). In the multivariate analysis, severe sepsis was the most significant predictor of mortality (RR=4.0 [2.2-7.7]) and uterine necrosis was the most significant predictor of hysterectomy (RR=6.3 [1.6-25.2]). There were high rates of antimicrobial resistance (AMR) among the bacterial isolates cultured from intra-abdominal pus, with 52% of bacteria resistant to third-generation cephalosporins.

Conclusions: Post-cesarean section peritonitis carries a high mortality rate in Rwanda. It is also associated with a high rate of hysterectomy. Understanding the disease process and identifying factors associated with outcomes can help guide management during admission.

Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres.

BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying array size. However, the average amount of CENP-A reported at human centromeres is largely consistent, implying the genomic extent of CENP-A chromatin domains more likely reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes within individual subdomains. Defining the organizational and spatial properties of CEN chromatin would provide insight into centromere inheritance via CENP-A loading in G1 and the dynamics of its distribution between mother and daughter strands during replication. RESULTS: Using a multi-color protein strategy to detect distinct pools of CENP-A over several cell cycles, we show that nascent CENP-A is equally distributed to sister centromeres. CENP-A distribution is independent of previous or subsequent cell cycles in that centromeres showing disproportionately distributed CENP-A in one cycle can equally divide CENP-A nucleosomes in the next cycle. Furthermore, we show using extended chromatin fibers that maintenance of the CENP-A chromatin domain is achieved by a cycle-specific oscillating pattern of new CENP-A nucleosomes next to existing CENP-A nucleosomes over multiple cell cycles. Finally, we demonstrate that the size of the CENP-A domain does not change throughout the cell cycle and is spatially fixed to a similar location within a given alpha satellite DNA array. CONCLUSIONS: We demonstrate that most human chromosomes share similar patterns of CENP-A loading and distribution and that centromere inheritance is achieved through specific placement of new CENP-A near existing CENP-A as assembly occurs each cell cycle. The loading pattern fixes the location and size of the CENP-A domain on individual chromosomes. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere identity and genome stability.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.