Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat

Peer reviewedPublisher PD

A common cause for a common phenotype : the gatekeeper hypothesis in fetal programming

Copyright © 2011 Elsevier Ltd. All rights reserved.Peer reviewedPublisher PD

The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport

Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA Sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life

Effects of land use change on the planform of the Kafubu river channel in Ndola urban, Zambia (1993-2015).

ThesisThis study sought to investigate the extent to which land use changes in Ndola Urban during the 22 years (1993-2015) have affected the planform of the Kafubu River using GIS and remote sensing techniques. The major objective was to assess the extent to which land use changes in Ndola urban have affected the size of the Kafubu River in the study period. For primary data, field observations on river channel were made and five local council planners as well as 13 respondents who had lived in Ndola for more than 20 years were interviewed for information on factors that may have caused land use and river planform changes. For secondary data aerial photographs taken in 1993 and 2015 and a 2009 IKONOS satellite image were used in assessing changes in land use and on the river morphology. The semi structured interviews were analysed using inductive thematic analysis. For analysis, aerial photographs covering the study area taken in 1993 and 2015 and a 2009 satellite image were georeferenced using 11ground control points. ArcGIS 10.5 software was used to generate object based classification land use maps which were later used to compare land use changes and river planform changes. A total of 10 evenly spaced transects were marked and made onto river polygons for each year to aid comparison of channel width with time using AutoCAD 2018. Findings of the study were that, most of the river buffer zone 50m on either side of the river had changed from crop land use to residential areas. The built up area had increased from 41.54ha in 1993 to 198.46ha (377.76%) in 2015 over the whole study period. Between the years 1993 and 2009 there was an increase in channel width at transects 6,7,8,9 and 10 while the other transects showed a width reduction. Similarly, between 2009 and 2015 there was an increase in channel width at transects 1, 2, 3 and 4 while reduction was observed at the other transects. For the entire study period the river width had reduced at all transects except at transects 2 and 10, in terms of channel growth or accretion and reduction due to erosion. The maximum annual rate of accretion was found to be 1.27m/year higher than that of erosion (maximum 0.2m/year) indicating an overall reduction in channel width. In terms of land coverage in the 22-year period, the surface area of Kafubu River reduced from 17.14ha in 1993 to 8.02ha (53.21%) by 2015. Factors attributed to causing land use changes were shortage of state land, corruption in allocation of land, proximity to central business district, population increase, ignorance of environmental issues, and poor planning by the Municipal Council. Similarly, channel planform changes were influenced by building houses in the buffer zone and by the expansion of the river Hyacinth weed. It is concluded that Kafubu River in the 22 years period has been affected by land use change in the river buffer zone from crop land to residential area which led to narrowing of channel width because of deposition of sediment into the river and consequently the reduction of the surface area of the river by 53.21 percent. It is recommended that the local government should implement strict land allocation policies, put more effort in water Hyacinth removal and protect the river buffer zone. Because of the inevitability of urbanisation, Kafubu River channel banks should be made permanent by construction of concrete banks in the town reach which will also protect residents from effects of flooding during wet years. Keywords: Remote Sensing, Accretion, Erosion, Kafubu Rive

Examining the impact of child labour on learning achievements in Uganda: a case study of two primary schools in Yumbe district

This study found out child labour in Uganda as a multi-dimensional challenge that deprives children of their childhood opportunities including right to quality education. It is a manifestation of extreme household poverty and socio-cultural practices making it to some extend invisible to detect and report. Government of Uganda accordingly, developed Legal Frameworks to combat the vice through Employment Act (2006), the National Action Plan (2012), and child labour policy (2006). These frameworks among other things allow children to do light work under the supervision of an adult and making education as a principle occupation of every child in Uganda. However, incidences’ of child labour still continue to manifest in Yumbe mainly in the areas of household chores and agriculture. The key study findings indicate that Child Labour is contributing to lowering of the learning achievements of working children in schools more than those of non-working children. It also creates gender disparities between boys and girls a potential ground for power imbalance in the socio-economic transformation of Yumbe District. Despite these challenges, there is limited advocacy and awareness on child labour and limited interventions by government, civil society organizations and social partners for children. This calls for a paradigm shift to providing holistic services to children at risk of child labour and their households. Child labour has limited space on local policy agenda in Sub-county and District Councils and Education Sector Reviews to inform planning and decision making processes of Local Governments. Deliberate capacity building is required to increase awareness on child rights in schools and communities. Finally, designing age appropriate livelihood opportunities for children engaged in child labour and their families’ would go a long way towards improving learning outcomes in Yumbe District

Exposure of neonatal rats to maternal cafeteria feeding during suckling alters hepatic gene expression and DNA methylation in the insulin signalling pathway

Nutrition in early life is a determinant of lifelong physiological and metabolic function. Diseases that are associated with ageing may, therefore, have their antecedents in maternal nutrition during pregnancy and lactation. Rat mothers were fed either a standard laboratory chow diet (C) or a cafeteria diet (O) based upon a varied panel of highly palatable human foods, during lactation. Their offspring were then weaned onto chow or cafeteria diet giving four groups of animals (CC, CO, OC, OO n=9-10). Livers were harvested 10 weeks post-weaning for assessment of gene and protein expression, and DNA methylation. Cafeteria feeding post-weaning impaired glucose tolerance and was associated with sex-specific altered mRNA expression of peroxisome proliferator activated receptor gamma (PPARg) and components of the insulin-signalling pathway (Irs2, Akt1 and IrB). Exposure to the cafeteria diet during the suckling period modified the later response to the dietary challenge. Post-weaning cafeteria feeding only down-regulated IrB when associated with cafeteria feeding during suckling (group OO, interaction of diet in weaning and lactation P=0.041). Responses to cafeteria diet during both phases of the experiment varied between males and females. Global DNA methylation was altered in the liver following cafeteria feeding in the post-weaning period, in males but not females. Methylation of the IrB promoter was increased in group OC, but not OO (P=0.036). The findings of this study add to a growing evidence base that suggests tissue function across the lifespan a product of cumulative modifications to the epigenome and transcriptome, which may be both tissue and sex-specific

Clinical estimation of fetal weight in the preterm population - an alternative to Leopold`s method validated by birth weight at the university teaching hospital, Lusaka

ThesisPreterm birth is defined as childbirth occurring at less than 36 completed weeks or 259 days of gestation (World Health Organization, 2014). In most developing and resource limited countries such as Zambia, ultrasound estimation of fetal weight in most circumstances is not readily available for the health care professional to make decisions, a gap which can be filled by a cheaper and simpler clinical method of estimation fetal weight. One such method is the Dare’s formula which relies on the product of the symphysio-fundal height and abdominal circumference to estimate the fetal weight. The study aimed at exploring this alternative clinical method to estimate fetal weight among women at highest risk of preterm birth in a low resource population and validate it with the actual birthweight. This was a prospective study on mothers admitted to University Teaching Hospital (UTH) at risk of preterm delivery. Between 1st June and 31st October 2016, a structured questionnaire was used to collect pregnancy and outcome data on a sample size of 168 mothers that had a singleton pregnancy, longitudinal lie and known gestation <37 weeks about to deliver within one week. Maternal anthropometrics included height, weight, abdominal circumference and fundal height. The derived (estimated) fetal weight calculated using Dare’s formula was compared to the actual birthweight. Paired t-test was used to compare the mean between derived and actual weights. Multivariate analysis was used to understand what maternal or pregnancy characteristics could have led to the variance (under and over-estimate beyond 300g or 10%). Of the 168 women enrolled, over half were moderate to late preterm (32 to 37 weeks) with 134 (79.8%) were between 32-37 weeks with 54.2% between 34-<37 weeks. Very Preterm were 29 (17.3%) and only 5 (3%) were <28 weeks. Using Dare’s formula. The derived birthweight was on average 553g greater than actual birthweight (SD = 641, 95% confidence interval 456– 651, p<0.0001). There was a 71.5% chance of variance beyond 300g. On multivariate analysis for every 1cm increase in fundal height measurement the odds for above 300g weight variance reduced on average by 14% (aOR =0.86, 95% CI = 0.76 - 0.98, P= 0.0249). Similarly, for every 1cm increase in maternal abdominal circumference measurement, the odds for above 300g weight difference increased on average by 7% [adjusted Odds Ratio (aOR) = 1.07, 95% Confidence Interval (CI) = 1.03 - 1.12, P= <0.001]. Based on this study population, this clinical method and using Dare’s formula cannot be reliably used in estimation of fetal weight in preterm pregnancies. Ultrasonography remains the gold standard for determining fetal weight in preterm pregnancies and should therefore be availed as part of the tools to help in counselling mothers on perinatal prognosis. Key words: Preterm birth, Fetal weight estimatio

Analysis of pre-weaning feeding policies and other risk factors influencing growth rates in calves on 11 commercial dairy farms

Growth rates in pre-weaned calves influence their health, age at first calving and lifetime productivity. Many farms restrict milk rations to encourage solid feed intake and facilitate early weaning, but this can compromise growth. This study determined the milk feeding policies and associated growth rates on 11 commercial dairy farms in South East England, each following their normal management regime. Between 26 and 54 heifers were recruited per farm, providing a final cohort of 492, of which 71% were pure Holstein. Information on calf rearing practices (feeding, weaning, housing) and health was collected via questionnaires and weekly observations. Estimates of actual milk fed (kg solids) between 1 and 63 days were calculated for individual calves. Morphometric data (weight, height, length) were taken at weeks 1, 5 and 9 and at a median age of 7.5 months and growth rates were calculated. Most calves were fed milk replacer via automated feeders (four farms), teat feeder (one) or buckets (four) whereas two farms provided drums of acidified waste milk. Farms fed between 4 and 6 l/day of milk at mixing rates of 10% to 15%, providing 400 to 900 g/day of milk solids. Both skeletal growth rates and average daily weight gain (ADG) increased in the second month of life compared with the first: height growth from 0.17±0.14 to 0.25±0.16 cm/day and ADG from 0.48±0.25 to 0.71±0.28 kg/day. Post-weaning heifers up to 7.5 months had height increases of 0.16±0.035 cm/day and ADG of 0.83±0.16 kg/day. From 1 to 63 days 70% of calves had growth rates <0.7 kg/day and of these 19.6% gained <0.5 kg/day. Mean ADG before 9 weeks varied between farms from 0.52±0.30 to 0.75±0.20 kg/day. This was related to the amount of milk fed at both a farm and individual calf level. Increasing the total milk solids fed between 1 and 63 days from 20.4 to 46.3 kg (the 10th to 90th percentile observed) was associated with an increase of 0.11 kg/day ADG. All farms had a wide variation in growth rates despite single feeding policies. Higher circulating immunoglobulin G and IGF1 concentrations were associated with better growth, whereas low temperatures in month of birth, high scores for diarrhoea, respiratory and umbilical disease and large birth size reduced growth. Many commercially grown dairy heifers therefore experienced growth restriction in the pre-weaned period, potentially reducing their health, welfare and productivity

LIM kinase function and renal growth: potential role for LIM kinases in fetal programming of kidney development

Aims Maternal dietary restriction during pregnancy impairs nephron development and results in offspring with fewer nephrons. Cell turnover in the early developing kidney is altered by exposure to maternal dietary restriction and may be regulated by the LIM-kinase family of enzymes. We set out to establish whether disturbance of LIM-kinase activity might play a role in the impairment of nephron formation. Main methods E12.5 metanephric kidneys and HK2 cells were grown in culture with the pharmacological LIM-kinase inhibitor BMS5. Organs were injected with DiI, imaged and cell numbers measured over 48 h to assess growth. Cells undergoing mitosis were visualised by pH 3 labelling. Key findings Growth of cultured kidneys reduced to 83% of controls after exposure to BMS5 and final cell number to 25% of control levels after 48 h. Whilst control and BMS5 treated organs showed cells undergoing mitosis (100 ± 11 cells/field vs 113 ± 18 cells/field respectively) the proportion in anaphase was considerably diminished with BMS5 treatment (7.8 ± 0.8% vs 0.8 ± 0.6% respectively; P < 0.01). This was consistent with effects on HK2 cells highlighting a severe impact of BMS5 on formation of the mitotic spindle and centriole positioning. DiI labelled cells migrated in 100% of control cultures vs 0% BMS5 treated organs. The number of nephrogenic precursor cells appeared depleted in whole organs and formation of new nephrons was blocked by exposure to BMS5. Significance Pharmacological blockade of LIM-kinase function in the early developing kidney results in failure of renal development. This is likely due to prevention of dividing cells from completion of mitosis with their resultant loss