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PubMed2004

The developmental bases of limb reduction and body elongation in squamates.

Employing an integrative approach to investigate the evolution of morphology can yield novel perspectives not attainable from a single field of study. Studies of limb loss and body elongation in squamates (snakes and lizards) present a good example in which integrating studies of systematics and ecology with genetics and development can provide considerable new insight. In this comment we address several misunderstandings of the developmental genetic literature presented in a paper by Wiens and Slingluff (2001) to counter their criticism of previous work in these disciplines and to clarify the apparently contradictory data from different fields of study. Specifically, we comment on (1) the developmental mechanisms underlying axial regionalization, body elongation, and limb loss; (2) the utility of presacral vertebral counts versus more specific partitioning of the primary body axis; (3) the independent, modular nature of limbs and limb girdles and their utility in diagnosing genetic changes in development; and (4) the causal bases of hind limb reduction in ophidian and nonophidian squamates.

Animals↗
PubMed2005

Functional specification in the Drosophila endoderm.

The discovery of homeobox gene clusters led us to realize that the mechanisms for body patterning and other developmental programs are evolutionally-conserved in vertebrates and invertebrates. The endoderm contributes to the lining of the gut and associated organs such as the liver and pancreas, which are critical for physiological functions. Our knowledge of endoderm development is limited; however, recent studies suggest that cooperation between the HNF3/Fork head and GATA transcription factors is crucial for endoderm specification. It is necessary to further understand the mechanism through which cells become functionally organized. Molecular genetic analyses of the Drosophila endoderm would provide insights into this issue. During proventriculus morphogenesis, a simple epithelial tube is folded into a functional multilayered structure, while two functions of midgut copper cells (i.e. copper absorption and acid secretion) can be easily visualized. The homeobox gene defective proventriculus (dve) plays key roles in these functional specifications.

Animals↗
PubMed1998

Pacing impedance variability in tined steroid eluting leads.

The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip.

Aged↗
PubMed2004

The effects of birth weight and postnatal growth patterns on fat depth and plasma leptin concentrations in juvenile and adult pigs.

Low birth weight is associated with altered adipose tissue deposition and regulation of leptin production. This study determined the effects of naturally occurring variations in birth weight in pigs on postnatal growth patterns, body fat depth and plasma leptin and other hormone concentrations. Low (< 1.47 kg) and high (> 1.53 kg) birth weight piglets were studied at 3 months (juvenile; n= 47) and 12 months of age (young adult; n= 17). At each age, arterial and venous catheters were inserted under general anaesthesia. Plasma leptin, cortisol, glucose, insulin and catecholamine concentrations were determined in basal blood samples. Body fat depth was measured by ultrasound at 12 months of age. Overall, adult fat depth was greater in low compared to high birth weight pigs and increased fat depth was associated with thinness at birth and poor early growth rates. These effects were strongest in females. Fat depth was related to current weight only in males. Compared to high birth weight pigs, plasma leptin concentrations were reduced in low birth weight females at 3 months and in low birth weight males at 12 months of age. This study demonstrates sex-specific effects of low birth weight on postnatal growth and body fatness and on plasma leptin concentrations in pigs.

Adipose Tissue↗
PubMed2004

Chromatin compaction by a polycomb group protein complex.

Polycomb group proteins preserve body patterning through development by maintaining transcriptional silencing of homeotic genes. A long-standing hypothesis is that silencing involves creating chromatin structure that is repressive to gene transcription. We demonstrate by electron microscopy that core components of Polycomb Repressive Complex 1 induce compaction of defined nucleosomal arrays. Compaction by Polycomb proteins requires nucleosomes but not histone tails. Each Polycomb complex can compact about three nucleosomes. A region of Posterior Sex Combs that is important for gene silencing in vivo is also important for chromatin compaction, linking the two activities. This mechanism of chromatin compaction might be central to stable gene silencing by the Polycomb group.

Chromatin↗
PubMed1992

Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.

The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.

Animals↗
PubMed2001

BSF binds specifically to the bicoid mRNA 3' untranslated region and contributes to stabilization of bicoid mRNA.

The early stages of Drosophila melanogaster development rely extensively on posttranscriptional forms of gene regulation. Deployment of the anterior body patterning morphogen, the Bicoid protein, requires both localization and translational regulation of the maternal bicoid mRNA. Here we provide evidence that the bicoid mRNA is also selectively stabilized during oogenesis. We identify and isolate a protein, BSF, that binds specifically to IV/V RNA, a minimal form of the bicoid mRNA 3' untranslated region that supports a normal program of mRNA localization during oogenesis. Mutations that disrupt the BSF binding site in IV/V RNA or substantially reduce the level of BSF protein lead to reduction in IV/V RNA levels, indicating a role for BSF in RNA stabilization. The BSF protein is novel and lacks all of the characterized RNA binding motifs. However, BSF does include multiple copies of the PPR motif, whose function is unknown but appears in other proteins with roles in RNA metabolism.

Amino Acid Sequence↗
PubMed2006

The tailless nuclear receptor acts as a dedicated repressor in the early Drosophila embryo.

Tailless is an orphan nuclear receptor that controls terminal body patterning in Drosophila. Genetic analyses have revealed both positive and negative regulatory interactions of Tailless with various target genes, leading to the idea that, like many other nuclear receptors, Tailless mediates both activation and repression of transcription. In this paper, we have examined the consequences of converting Tailless into an obligate repressor and compared the activities of the resulting protein with those of wild-type Tailless. We find that this repressor form of Tailless behaves like the intact protein in gain- and loss-of-function experiments, being sufficient to support normal embryonic development and establish accurate patterns of gene expression even for positive Tailless targets such as hunchback and brachyenteron. This suggests that Tailless functions exclusively as a transcriptional repressor in the embryo and that the observed positive interactions of Tailless with specific targets are secondary effects involving repression of repressors. We provide evidence that knirps is one such repressor gene acting between Tailless and its indirect positive targets. Finally, our results indicate that Tailless exerts an active mechanism of repression via its ligand-binding domain and that this activity is largely independent of the activation function 2 (AF2) motif characteristic of most nuclear receptors.

Amino Acid Sequence↗
PubMed1999

Cytoplasmic polyadenylation in development and beyond.

Maternal mRNA translation is regulated in large part by cytoplasmic polyadenylation. This process, which occurs in both vertebrates and invertebrates, is essential for meiosis and body patterning. In spite of the evolutionary conservation of cytoplasmic polyadenylation, many of the cis elements and trans-acting factors appear to have some species specificity. With the recent isolation and cloning of factors involved in both poly(A) elongation and deadenylation, the underlying biochemistry of these reactions is beginning to be elucidated. In addition to early development, cytoplasmic polyadenylation is now known to occur in the adult brain, and there is circumstantial evidence that this process occurs at synapses, where it could mediate the long-lasting phase of long-term potentiation, which is probably the basis of learning and memory. Finally, there may be multiple mechanisms by which polyadenylation promotes translation. Important questions yet to be answered in the field of cytoplasmic polyadenylation are addressed.

Animals↗
PubMed2005

Subdural haematoma and effusion in infancy: an epidemiological study.

AIM: To determine incidence, aetiology, and clinical features of subdural haematoma and effusion (SDH/E) in infancy throughout the British Isles. METHODS: Cases were notified to the British Paediatric Surveillance Unit over 12 months by paediatricians, neurosurgeons, and paediatric and forensic pathologists. RESULTS: A total of 186 infants (121 boys, 65 girls) aged 0-2 years were identified. Annual incidence of SDH/E for the UK and Republic of Ireland is 12.54/100,000 aged 0-2 (95% CI 10.3 to 14.62) and 24.1/100,000 aged 0-1 (95% CI 20.89 to 28.18). A total of 106 infants suffered non-accidental head injury (NAHI), 7 accidental head injury, 26 a perinatal cause, 7 a non-traumatic medical condition, 23 meningitis, and in 17 the cause was undetermined; 35 infants died. Significant differences were found in injury pattern, body weight, and Townsend score between NAHI and SDH/E from other cause. There were fewer diagnostic investigations in non-NAHI cases. Delay in diagnosis of greater than a week occurred in 48/181. CONCLUSION: SDH/E is a significant cause of morbidity and mortality in infancy. NAHI is the predominant cause of SDH/E. SDH/E can present in a non-specific and varied way and must be considered in any infant who is unwell. Determining the cause of the SDH/E in some cases continues to present a diagnostic challenge.

Child Abuse↗
PubMed1993

Relationship between smoking, weight and attitudes to weight in adolescent schoolgirls.

A total of 1,932 schoolgirls aged 11-18 from seven schools in the South London area were surveyed using questionnaires which addressed eating patterns, body weight history, attitudes to body weight and shape, menstrual history and current smoking behaviour. They were also weighed and their height was measured. Twelve per cent of the girls were regular smokers and 10% smoked seven or more cigarettes over a 4 day period. Amongst girls aged 14 and over, 15% smoked regularly and a further 9% occasionally. A significant relationship was found between smoking and weight. Smokers were more likely to be moderately overweight in relation to their peers and to have been worried about their weight at some stage. There were differences between girls in state schools and those in independent schools with regard to smoking behaviour and weight. The findings have implications for anti-smoking strategies and health education generally.

Adolescent↗
PubMed1999

Drink composition, voluntary drinking, and fluid balance in exercising, trained, heat-acclimatized boys.

This study examined the effects of beverage composition on the voluntary drinking pattern, body fluid balance, and thermoregulation of heat-acclimatized trained boys exercising intermittently in outdoor conditions (wet bulb globe temperature 30.4 +/- 1.0 degreesC). Twelve boys (age 13.4 +/- 0.4 yr) performed two 3-h sessions, each consisting of four 20-min cycling bouts at 60% maximal aerobic power alternating with 25-min rest. One of two beverages was assigned: unflavored water (W) or flavored water plus 6% carbohydrate and 18 mmol/l Na (CNa). Drinking was ad libitum. Total intake was higher (P < 0.05) during CNa (1,943 +/- 190 g) compared with W (1,470 +/- 143 g). Euhydration was maintained with CNa (+0.18% body wt), but a mild dehydration resulted with W (-0.94% body wt; P < 0.05). Sweat loss, much higher than previously published for children of similar age, was similar between conditions (CNa = 1,644.7 +/- 117.5; W = 1,750.2 +/- 152.7 g). The increase in rectal temperature (CNa = 0.86 +/- 0.3; W = 0.76 +/- 0.1 degreesC), heart rate, and all perceptual variables did not differ between conditions. In conclusion, a flavored carbohydrate-electrolyte drink prevents voluntary dehydration in trained heat-acclimatized boys exercising in a tropical climate despite their large sweat losses. Because hydration changes were minor, the thermoregulatory strain observed was similar between conditions.

Acclimatization↗
PubMed2003

Conservation of regulatory elements between two species of Drosophila.

BACKGROUND: One of the important goals in the post-genomic era is to determine the regulatory elements within the non-coding DNA of a given organism's genome. The identification of functional cis-regulatory modules has proven difficult since the component factor binding sites are small and the rules governing their arrangement are poorly understood. However, the genomes of suitably diverged species help to predict regulatory elements based on the generally accepted assumption that conserved blocks of genomic sequence are likely to be functional. To judge the efficacy of strategies that prefilter by sequence conservation it is important to know to what extent the converse assumption holds, namely that functional elements common to both species will fall within these conserved blocks. The recently completed sequence of a second Drosophila species provides an opportunity to test this assumption for one of the experimentally best studied regulatory networks in multicellular organisms, the body patterning of the fly embryo. RESULTS: We find that 50%-70% of known binding sites reside in conserved sequence blocks, but these percentages are not greatly enriched over what is expected by chance. Finally, a computational genome-wide search in both species for regulatory modules based on clusters of binding sites suggests that genes central to the regulatory network are consistently recovered. CONCLUSIONS: Our results indicate that binding sites remain clustered for these "core modules" while not necessarily residing in conserved blocks. This is an important clue as to how regulatory information is encoded in the genome and how modules evolve.

Algorithms↗
PubMed2006

Irregular breakfast eating and health status among adolescents in Taiwan.

BACKGROUND: Regular breakfast eating (RBE) is an important contributor to a healthy lifestyle and health status. The aims of the present study were to evaluate the relationships among irregular breakfast eating (IRBE), health status, and health promoting behavior (HPB) for Taiwanese adolescents. METHODS: A cross-sectional, descriptive design was used to investigate a cluster sample of 1609 (7th-12th grade) adolescents located in the metropolitan Tao-Yuan area during the 2005 academic year. The main variables comprised breakfast eating pattern, body weight, and health promoting behaviors. Data were collected by a self-administered questionnaire. RESULTS: A total of 1609 participants were studied, 64.1% in junior high school and 35.9% in high school, boys (47.1%) and girls (52.9%) ranging in age from 12-20 years. Of the total participant population, 28.8% were overweight and nearly one quarter (23.6%) reported eating breakfast irregularly during schooldays. The findings indicated that adolescents with RBE had a lower risk of overweight (OR for IRBE vs. RBE = 1.51, 95% CI: 1.12, 2.04), and that the odds of becoming overweight were 51% greater for IRBE than for RBE even after controlling for demographical and HPB variables. IRBE also was a strong indicator for HPB. However, the profile of the high-risk IRBE group was predominantly junior high schoolchildren and/or children living without both parents. CONCLUSION: This study provides valuable information about irregular breakfast eating among adolescents, which is associated with being overweight and with a low frequency of health promoting behavior. School and family health promotion strategies should be used to encourage all adolescents to eat breakfast regularly.

Adolescent↗
PubMed2006

The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina)--phenotypic manifestations and genetic approaches.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome.

Abnormalities, Multiple↗
PubMed2004

Identification of chaperonin CCT gamma subunit as a determinant of retinotectal development by whole-genome subtraction cloning from zebrafish no tectal neuron mutant.

Zebrafish no tectal neuron (ntn) mutant obtained by trimethylpsoralen (TMP) mutagenesis showed defects in tectal neuropil formation and small eyes. We carried out whole-genome subtraction between wild-type and mutant zebrafish embryos using the representational difference analysis (RDA) method. Nineteen subtraction products enabled us to construct genetic and physical maps of the ntn region. Direct selection of cDNAs using a YAC clone encompassing the ntn locus and RT-PCR analysis of transcripts identified a 143 bp deletion in the cct3 gene encoding the gamma subunit of chaperonin containing TCP-1 (CCT). Injection of antisense cct3 morpholino oligonucleotides into zebrafish embryos induced characteristic ntn phenotypes including defects in retinal ganglion cell (RGC) differentiation and tectal neuropil formation. Moreover, injection of cct3 mRNA successfully rescued ntn mutant embryos. Our results suggest that RDA is an efficient and widely applicable cloning strategy in zebrafish genetics. The strong expression of the cct3 mRNA started in the entire embryos by 12 hpf and was sustained thereafter, but there were no detectable abnormalities in body patterning and neurogenesis in ntn mutant embryos at 30 hpf. The expression patterns of transcription factor genes ath5 and brn3b that are essential for the development and maintenance of RGCs were indistinguishable between wild-type and ntn mutant embryos, but those of early and late differentiation markers of RGCs, nicotinic acetylcholine receptor beta 3 and zn5, were diminished in mutant embryos. Immunostaining of acetylated tubulin also revealed the impairment of RGC neurite extension. Thus, the ntn mutation of the cct3 gene impaired the differentiation of retinal neuroepithelial cells to RGCs. Similarly, the expression of brn3b was normal in the tectum of ntn mutants, but tectal neuropil formation was abolished. These results suggest that the gamma subunit of chaperonin CCT plays an essential role in retinotectal development.

Amino Acid Sequence↗
PubMed2004

Temporal complexity within a translational control element in the nanos mRNA.

Translational control of gene expression plays a fundamental role in the early development of many organisms. In Drosophila, selective translation of nanos mRNA localized to the germ plasm at the posterior of the embryo, together with translational repression of nanos in the bulk cytoplasm, is essential for development of the anteroposterior body pattern. We show that both components to spatial control of nanos translation initiate during oogenesis and that translational repression is initially independent of Smaug, an embryonic repressor of nanos. Repression during oogenesis and embryogenesis are mediated by distinct stem loops within the nanos 3' untranslated region; the Smaug-binding stem-loop acts strictly in the embryo, whereas a second stem-loop functions in the oocyte. Thus, independent regulatory modules with temporally distinct activities contribute to spatial regulation of nanos translation. We propose that nanos evolved to exploit two different stage-specific translational regulatory mechanisms.

3' Untranslated Regions↗
PubMed2006

The roles of cilia in developmental disorders and disease.

Cilia are highly conserved organelles that have diverse motility and sensory functions. Recent discoveries have revealed that cilia also have crucial roles in cell signaling pathways and in maintaining cellular homeostasis. As such, defects in cilia formation or function have profound effects on the development of body pattern and the physiology of multiple organ systems. By categorizing syndromes that are due to cilia dysfunction in humans and from studies in vertebrate model organisms, molecular pathways that intersect with cilia formation and function have come to light. Here, we summarize an emerging view that in order to understand some complex developmental pathways and disease etiologies, one must consider the molecular functions performed by cilia.

Animals↗