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Biomedical subjects

E L Ferguson

Publications and source records attributed to E L Ferguson.

At least 19 recordsLinked to original sources
PubMed2005

Do young New Zealand Pacific Island and European children differ in bone size or bone mineral?

Although Pacific Island adults have been shown to have larger bones and greater bone mineral density than caucasians, no previous studies have been undertaken to determine whether differences are present in prepubertal children. Forty-one Pacific Island children (both parents of Pacific Island descent) and 38 European children, aged 3 to 7 years, living in New Zealand were studied. Heights and weights were determined by simple anthropometry and body mass index (BMI, kg/m2) was calculated. Body composition, bone size, and bone mineral content (BMC, g) were measured by dual energy X-ray absorptiometry (DXA) of the total body and the non-dominant forearm. Compared to European children, in data adjusted for age and gender, Pacific Island children had significantly greater (P < 0.05) BMC in the total body (12%), the ultradistal radius (16%), and the 33% radius (8%), and also greater total body bone area (10%). Bone mineral density (BMD, g/cm2) was higher only at the ultradistal radius (11%). However, after adjustment for body weight, in particular lean mass, no differences were seen between Pacific Island and European children in any bone measure. The larger bone area and BMC of young Pacific Island children can be explained by their greater height and weight. Therefore, this study has shown that prepubertal Pacific Island children do not have greater bone size or BMC for their weight.

Absorptiometry, Photon↗
PubMed2004

Iron deficiency and risk factors for lower iron stores in 6-24-month-old New Zealanders.

OBJECTIVES: To determine the prevalence of biochemical iron deficiency and identify factors associated with ferritin levels among 6-24-month-old urban South Island New Zealand children. DESIGN: Cross-sectional survey conducted from May 1998 to March 1999. SETTING: The cities of Christchurch, Dunedin and Invercargill. SUBJECTS: A total of 323 randomly selected 6-24-month-old children participated (response rate 61%) of which 263 provided a blood sample. METHODS: A complete blood cell count, zinc protoporphyrin, serum ferritin and C-reactive protein were measured on nonfasting venipuncture blood samples, 3-day weighed food records and general questionnaire data were collected. RESULTS: Among children with C-reactive protein<10 mg/l (n=231), 4.3% had iron deficiency anaemia, 5.6% had iron deficiency without anaemia, and 18.6% had depleted iron stores, when a ferritin cutoff of < or =12 g/l was used. Age (negative), sex (girls>boys), ethnicity (Caucasian>non-Caucasian), weight-for-age percentiles (negative) and birth weight (positive) were associated with ferritin after adjusting for infection and socioeconomic status. When current consumption of iron fortified formula and >500 ml of cows' milk per day were included, these were associated with a 22% increase and 25% decrease in ferritin, respectively (R2=0.28). CONCLUSIONS: The presence of suboptimal iron status (29%) among young New Zealand children is cause for concern, even though severe iron deficiency is rare, because children with marginal iron status are at risk of developing severe iron deficiency if exposed to a physiological challenge.

Anemia, Iron-Deficiency↗
PubMed2002

Risk of suboptimal iron and zinc nutriture among adolescent girls in Australia and New Zealand: causes, consequences, and solutions.

Surveys in Australia, New Zealand and other industrialised countries report that many adolescent girls have dietary intakes of iron and zinc that fail to meet their high physiological requirements for growing body tissues, expanding red cell mass, and onset of menarche. Such dietary inadequacies can be attributed to poor food selection patterns, and low energy intakes. Additional exacerbating non-dietary factors may include high menstrual losses, strenuous exercise, pregnancy, low socioeconomic status and ethnicity. These findings are cause for concern because iron and zinc play essential roles in numerous metabolic functions and are required for optimal growth, immune and cognitive function, work capacity, sexual maturation, and bone mineralization. Moreover, if adolescents enter pregnancy with a compromised iron and zinc status, and continue to receive intakes of iron and zinc that do not meet their increased needs, their poor iron and zinc status could adversely affect the pregnancy outcome. Clearly, intervention strategies may be needed to improve the iron and zinc status of high risk adolescent subgroups in Australia and New Zealand. The recommended treatment for iron deficiency anaemia and moderate zinc deficiency is supplementation. Although dietary intervention is often recommended for treating non-anaemic iron deficiency and mild zinc deficiency, it is probably more effective and appropriate for prevention than for the treatment of suboptimal iron and zinc status. Many of the strategies for enhancing the content and bioavailability of dietary iron are also appropriate for zinc.

Adolescent↗
PubMed2001

Dietary iron intakes and biochemical iron status of 15-49 year old women in New Zealand: is there a cause for concern?

AIM: To assess dietary iron intakes and biochemical iron status of a nationally representative sample of nonpregnant 15-49 year old women (n=1,751) in New Zealand. METHODS: A cross-sectional national survey was conducted in 1996/97. Women were selected via a multistage stratified cluster sampling procedure with increased sampling of Maori and Pacific women. Dietary iron intakes were estimated using a 24-hour diet recall. Biochemical iron status was assessed on a non-fasting venipuncture blood sample (n=1,047) via haemoglobin, mean cell volume, erythrocyte zinc protoporphyrin, transferrin receptors and serum ferritin. RESULTS: Average daily dietary iron intakes ranged from 9.6 mg/day among Pacific women to 10.5 mg/day among Maori women; 41% of 20-49 year olds and 45% of adolescents were at risk of low dietary iron intakes. The estimated percentage of 15-49 year old women with iron deficiency anaemia ranged from 1.4-5.5%, and for iron deficiency without anaemia from 0.7-12.6% depending on the age group and criteria used. CONCLUSIONS: The overall estimated prevalence of suboptimal biochemical iron status among 15-49 year old women in New Zealand ranged from 7-13%, which compared favourably with premenopausal women living in other western countries. This situation is, however, a public health concern given the potential negative functional consequences associated with even mild iron deficiency.

Adolescent↗
PubMed2001

The DSmurf ubiquitin-protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis.

We identified Drosophila Smurf (DSmurf) as a negative regulator of signaling by the BMP2/4 ortholog DPP during embryonic dorsal-ventral patterning. DSmurf encodes a HECT domain ubiquitin-protein ligase, homologous to vertebrate Smurf1 and Smurf2, that binds the Smad1/5 ortholog MAD and likely promotes its proteolysis. The essential function of DSmurf is restricted to its action on the DPP pathway. DSmurf has two distinct, possibly mechanistically separate, functions in controlling DPP signaling. Prior to gastrulation, DSmurf mutations cause a spatial increase in the DPP gradient, as evidenced by ventrolateral expansion in expression domains of target genes representing all known signaling thresholds. After gastrulation, DSmurf mutations cause a temporal delay in downregulation of earlier DPP signals, resulting in a lethal defect in hindgut organogenesis.

Animals↗
PubMed2001

Selenium and zinc status are suboptimal in a sample of older New Zealand women in a community-based study.

The importance of selenium and zinc in the immune functioning of the aged is widely recognized. Seniors in New Zealand are at particularly high risk of low selenium status because of the low selenium soil environment. The zinc status of the New Zealand elderly has never been assessed. In this cross-sectional study, the biochemical selenium, zinc and lipid levels, physical functional capacity and dietary intakes of 103 randomly selected free-living New Zealand women (mean age +/- SD, 75 +/- 3 y) were assessed. Among nonusers of selenium supplements (n = 80), 80% [95% confidence interval (CI): 70; 88%] had plasma selenium levels (0.85 +/- 0.23 micromol/L) below 1.00 micromol/L [ approximately 10% below mean plasma selenium necessary for full expression of glutathione peroxidase (GPx) activity in New Zealand subjects]. Plasma selenium was strongly correlated with GPx: r = 0.56; P < 0.0001. For nonusers of zinc supplements (n = 88), serum zinc concentrations were 12.4 +/- 1.4 micromol/L, with 12% (95% CI: 6; 21%) having levels below the cut-off value (10.7 micromol/L). Estimated mean daily selenium and zinc intakes were 34 +/- 10 microg and 8.7 +/- 2.0 mg, respectively. Subjects in the highest tertile of a functional capacity index had higher biochemical zinc and selenium values than those in the lowest tertile (P < 0.05). The correlation between plasma selenium and GPx indicates that selenium intake in these women is still insufficient for full expression of GPx activity. Lower serum zinc levels also appear to be prevalent. Because a suboptimal trace element status may be more common among those with a poor physical functioning, promotion of the consumption of nutrient dense foods or supplements to improve selenium and zinc status of elderly women in New Zealand may be beneficial.

Aged↗
PubMed2001

A positive role for Short gastrulation in modulating BMP signaling during dorsoventral patterning in the Drosophila embryo.

Positional information in the dorsoventral axis of the Drosophila embryo is encoded by a BMP activity gradient formed by synergistic signaling between the BMP family members Decapentaplegic (DPP) and Screw (SCW). short gastrulation (sog), which is functionally homologous to Xenopus Chordin, is expressed in the ventrolateral regions of the embryo and has been shown to act as a local antagonist of BMP signaling. Here we demonstrate that SOG has a second function, which is to promote BMP signaling on the dorsal side of the embryo. We show that a weak, homozygous-viable sog mutant is enhanced to lethality by reduction in the activities of the Smad family members Mad or Medea, and that the lethality is caused by defects in the molecular specification and subsequent cellular differentiation of the dorsal-most cell type, the amnioserosa. While previous data had suggested that the negative function of SOG is directed against SCW, we present data that suggests that the positive activity of SOG is directed towards DPP. We demonstrate that Chordin shares the same apparent ligand specificity as does SOG, preferentially inhibiting SCW but not DPP activity. However, in Drosophila assays Chordin does not have the same capacity to elevate BMP signaling as does SOG, identifying a functional difference in the otherwise well conserved process of dorsoventral pattern formation in arthropods and chordates.

Animals↗
PubMed1999

Morphogen gradients: new insights from DPP.

The Drosophila TGFbeta family member Decapentaplegic (DPP) has been proposed to function as a morphogen to pattern cell fields in a number of developmental contexts. A series of recent reports add significantly to our knowledge of the mechanisms of DPP-gradient formation and interpretation. These reports identity additional genes and genetic circuitry necessary for this patterning system, and they highlight variations that might reflect developmental constraints within individual target cell fields.

Animals↗
PubMed1998

Spatially restricted activation of the SAX receptor by SCW modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning.

Dorsal-ventral patterning within the embryonic ectoderm of Drosophila requires two TGFbeta ligands, DPP and SCW, and two type I TGFbeta receptors, TKV and SAX. In embryos lacking dpp signaling, increasing the level of TKV activity promotes progressively more dorsal cell types, while activation of SAX alone has no phenotypic consequences. However, SAX activity synergizes with TKV activity to promote dorsal development. Functional experiments suggest the two receptors have different ligands: DPP acts through TKV, and SCW acts through SAX. Furthermore, SOG, a negative regulator of this patterning process, preferentially blocks SCW activity. We propose that spatial regulation of the SAX pathway modulates TKV signaling to create positional information over the embryonic ectoderm.

Animals↗
PubMed1998

Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm.

Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and function of the homeobox gene tinman in dorsal mesodermal cells during early embryogenesis. Here we present a functional dissection of a tinman enhancer that mediates the Dpp response. We provide evidence that mesoderm-specific induction of tinman requires the binding of both activators and repressors. Screens for binding factors yielded Tinman itself and the Smad4 homolog Medea. We show that the binding and synergistic activities of Smad and Tinman proteins are critical for mesodermal tinman induction, whereas repressor binding sites prevent induction in the dorsal ectoderm and amnioserosa. Thus, integration of positive and negative regulators on enhancers of target genes appears to be an important mechanism in tissue-specific induction by TGF-beta molecules.

Amino Acid Sequence↗
PubMed1998

Complementary foods for infant feeding in developing countries: their nutrient adequacy and improvement.

OBJECTIVE: To assess the energy and nutrient adequacy of a variety of complementary foods used in parts of Africa, India, Papua New Guinea, the Philippines and Thailand. METHOD: The energy, nutrient and anti-nutrient (dietary fibre and phytic acid) content (per 100 g as eaten, per 100 kcal, and per day) of twenty-three plant-based complementary foods consumed in developing countries was calculated from food composition values based on chemical analysis for the trace minerals, non-starch polysaccharide and phytic acid, and the literature. Results were compared with the estimated nutrient needs (per day; per 100 kcal) from complementary foods for infants 9-11 months, assuming a breast milk intake of average volume and composition and three complementary feedings per day, each of 250 g. RESULTS: Complementary foods should provide approximately 25-50% of total daily requirements for protein, riboflavin and copper; 50-75% for thiamin, calcium and manganese; and 75-100% for phosphorus, zinc and iron. Most or all appear to meet the estimated daily nutrient needs (per day; per 100 kcal) from complementary foods for protein, thiamin and copper (per day), but not for calcium, iron, and in some cases zinc, even if moderate bioavailability for iron and zinc is assumed. Some of those based on rice are also inadequate in riboflavin (per day; per 100 kcal). CONCLUSIONS: Even if strategies to improve the bioavailability of iron and zinc are employed, they are probably insufficient to overcome the deficits in calcium, iron and zinc. Therefore, research on the feasibility of fortifying plant-based complementary foods in developing countries with calcium, iron and zinc is urgently required.

Africa↗
PubMed1998

Assessment of dietary zinc in a population.

Assessment of dietary zinc status in a population requires several steps, consisting of the measurement of food intake distributions in the population; the analysis of local staple foods, from which zinc intake distributions can be determined, and the comparison of zinc intakes with requirement estimates to determine the risk of inadequate intakes. In low-income countries, these steps may be complicated by the lack of preexisting food-composition data, variations in food preparation methods, inhibition of absorption by other compounds in the diet, and variations in intake among seasons, individuals, and populations. Different techniques for determining the adequacy of zinc intake are compared. Whereas the techniques described in this paper allow for the determination of probability estimates for risk of zinc inadequacy, they do not allow for the identification of actual individuals in a population who are zinc deficient, or define the severity of zinc inadequacy. This information is vital, especially in areas where zinc deficiency is but one of many health problems, and can be obtained only from more detailed biochemical and physiologic studies of zinc status.

Biological Availability↗
PubMed1998

The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4.

The Transforming Growth Factor-beta superfamily member decapentaplegic (dpp) acts as an extracellular morphogen to pattern the embryonic ectoderm of the Drosophila embryo. To identify components of the dpp signaling pathway, we screened for mutations that act as dominant maternal enhancers of a weak allele of the dpp target gene zerknŁllt. In this screen, we recovered new alleles of the Mothers against dpp (Mad) and Medea genes. Phenotypic analysis of the new Medea mutations indicates that Medea, like Mad, is required for both embryonic and imaginal disc patterning. Genetic analysis suggests that Medea may have two independently mutable functions in patterning the embryonic ectoderm. Complete elimination of maternal and zygotic Medea activity in the early embryo results in a ventralized phenotype identical to that of null dpp mutants, indicating that Medea is required for all dpp-dependent signaling in embryonic dorsal-ventral patterning. Injection of mRNAs encoding DPP or a constitutively activated form of the DPP receptor, Thick veins, into embryos lacking all Medea activity failed to induce formation of any dorsal cell fates, demonstrating that Medea acts downstream of the thick veins receptor. We cloned Medea and found that it encodes a protein with striking sequence similarity to human SMAD4. Moreover, injection of human SMAD4 mRNA into embryos lacking all Medea activity conferred phenotypic rescue of the dorsal-ventral pattern, demonstrating conservation of function between the two gene products.

Amino Acid Sequence↗
PubMed1997

Fish are like flies are like frogs: conservation of dorsal-ventral patterning mechanisms.

Genetic analysis of Drosophila has shown that a morphogenetic gradient of the Transforming Growth Factor-beta family member dpp patterns the embryonic dorsal-ventral axis. Molecular and embryological evidence from Xenopus has strongly suggested a similar role for Bmp-4, the dpp homolog, in patterning the dorsal-ventral axis of chordates. A recent report has now identified mutations in two genes, dino and swirl, that disrupt dorsal-ventral patterning in the zebrafish Danio rerio. Characterization of these mutations parallels findings from Drosophila, thus establishing a genetic framework for the analysis of dorsal-ventral patterning in a vertebrate.

Animals↗
PubMed1997

Identification and characterization of genes that interact with lin-12 in Caenorhabditis elegans.

We identified and characterized 14 extragenic mutations that suppressed the dominant egg-laying defect of certain lin-12 gain-of-function mutations. These suppressors defined seven genes: sup-17, lag-2, sel-4, sel-5, sel-6, sel-7 and sel-8. Mutations in six of the genes are recessive suppressors, whereas the two mutations that define the seventh gene, lag-2, are semi-dominant suppressors. These suppressor mutations were able to suppress other lin-12 gain-of-function mutations. The suppressor mutations arose at a very low frequency per gene, 10-50 times below the typical loss-of-function mutation frequency. The suppressor mutations in sup-17 and lag-2 were shown to be rare non-null alleles, and we present evidence that null mutations in these two genes cause lethality. Temperature-shift studies for two suppressor genes, sup-17 and lag-2, suggest that both genes act at approximately the same time as lin-12 in specifying a cell fate. Suppressor alleles of six of these genes enhanced a temperature-sensitive loss-of-function allele of glp-1, a gene related to lin-12 in structure and function. Our analysis of these suppressors suggests that the majority of these genes are part of a shared lin-12/glp-1 signal transduction pathway, or act to regulate the expression or stability of lin-12 and glp-1.

Animals↗
PubMed1996

The Xenopus dorsalizing factor noggin ventralizes Drosophila embryos by preventing DPP from activating its receptor.

noggin is expressed in the Spemann organizer region of the Xenopus embryo and can promote dorsal cell fates within the mesoderm and neural development within the overlying ectoderm. Here, we show that noggin promotes ventral development in Drosophila, specifying ventral ectoderm and CNS in the absence of all endogenous ventral-specific zygotic gene expression. We utilize constitutively active forms of the dpp receptors to demonstrate that noggin blocks dpp signaling upstream of dpp receptor activation. These results suggest a mechanistic basis for the action of Spemann's organizer during Xenopus development and provide further support for the conservation of dorsal-ventral patterning mechanisms between arthropods and chordates.

Activin Receptors↗
PubMed1996

Conservation of dorsal-ventral patterning in arthropods and chordates.

Dorsal-ventral patterning within the ectodermal and mesodermal germ layers of Drosophila and Xenopus embryos is specified by a system of genes that has been conserved over 500 million years of evolution. In both organisms, the activity of the TGF-beta family member DPP/BMP4 is antagonized by SOG/CHORDIN. A second Xenopus gene, noggin, has a similar biological activity to chordin. Analysis of the action of these genes indicate that Spemann's organizer promotes dorsal cell fates in Xenopus by antagonizing a ventralizing signal encoded by the Bmp4 gene.

Animals↗