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Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps.

The body pattern along the anterior-posterior axis of the insect embryo is thought to be established by two organizing centres localized at the ends of the egg. Genetic analysis of the polarity-organizing centres in Drosophila has identified three distinct classes of maternal effect genes that organize the anterior, posterior and terminal pattern elements of the embryo. The factors provided by these gene classes specify the patterns of expression of the segmentation genes at defined positions along the longitudinal axis of the embryo. The system responsible for organizing the posterior segment pattern is a group of at least seven maternal genes and the zygotic gap gene knirps (kni). Their mutant phenotype has adjacent segments in the abdominal region of the embryo deleted. Genetic analysis and cytoplasmic transplantation experiments suggested that these maternal genes are required to generate a 'posterior activity' that is thought to activate the expression of kni (reviewed in ref. 2). The molecular nature of the members of the posterior group is still unknown. Here we report the molecular characterization of the kni gene that codes for a member of the steroid/thyroid receptor superfamily of proteins which in vertebrates act as ligand-dependent DNA-binding transcription regulators.

Abdomen

Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development.

Amino Acid Sequence

Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis.

runt is one of the genes required for establishment of the segmented body pattern of the Drosophila embryo. We have isolated DNA sequences containing this gene using P-element transposon tagging. Southern blot analyses of six different DNA rearrangements that are associated with runt mutations revealed a minimal region of 8.5-kb of DNA that was important for function. In germ line transformation experiments, a 14.5-kb segment of DNA that spanned this minimal region provided significant, although not full, levels of runt activity. The runt gene encoded a 2.6-kb poly(A)+ RNA that underwent a series of dynamic changes in its spatial and temporal patterns of accumulation during embryogenesis. The runt RNA was most abundant at the blastoderm stage when it showed the seven stripes of expression characteristic of other Drosophila pair-rule genes.

Animals

The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system.

Generation of the anterior-posterior body pattern in the Drosophila embryo requires the activity of the segmentation genes. The segmentation gene runt has been classified as one of the primary pair-rule genes because of the pivotal role it plays in regulating the expression of other pair-rule genes. Here, we present the structure of this gene and describe the pattern of runt protein expression during embryogenesis. The deduced protein sequence shows no obvious overall homology with any sequences in the data base. The absence of an identifiable transcription factor motif (e.g., homeo box, zinc finger, leucine zipper, or helix-loop-helix) makes runt different from the other early-acting segmentation proteins. A runt-specific polyclonal antibody was generated and used to demonstrate that the subcellular location of the protein is in the nucleus. Double-staining immunolocalization experiments were used to determine the overlap of the runt protein pattern with the patterns of the pair-rule genes hairy (h), even-skipped (eve), and fushi tarazu (ftz). We found that the patterns of runt and hairy are complementary. Their phasing is shifted anteriorly by two cell diameters with respect to the complementary eve and ftz patterns. Experiments with the runt antibody also indicated that the protein is present throughout embryogenesis and is expressed extensively in the developing central and peripheral nervous system.

Amino Acid Sequence

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

Anterior determinants in embryos of Chironomus samoensis: characterization by rescue bioassay.

Embryos of Chironomus samoensis are programmed, by anterior u.v. irradiation, to form the abnormal body pattern 'double abdomen'. Most double abdomen embryos show a mirror-image duplication of abdominal segments in the absence of cephalic or thoracic segments. Such embryos can be 'rescued', i.e. restored to normal development, by microinjection of cytoplasm or RNA from unirradiated donor embryos. Most of the rescued embryos look completely normal and many of them hatch spontaneously. The rescuing activity decreases from the anterior to the posterior pole in the donor cytoplasm and must be delivered near the anterior pole of the recipient for maximum efficiency. Rescuing activity is present in total RNA extracted from whole, unirradiated embryos. Upon fractionation, the activity is associated with poly(A)+ RNA, with LiCl precipitate depleted of RNA smaller than 250 nucleotides (nt) and with a sucrose gradient fraction depleted of RNA larger than 500 nt. Corresponding fractions of RNA from Xenopus oocytes have no rescuing activity. The activity of Chironomus RNA is sensitive to u.v. irradiation with low fluence affecting less than 2% of the pyrimidine bases. Rescuing activity is present in cytoplasm until the blastoderm stage but disappears earlier from poly(A)+ RNA. Rescuing activity is also present, and localized, in cytoplasm of embryos from two related dipterans, Smittia sp. and Drosophila melanogaster, although the extent of rescue observed in Chironomus decreases with the phylogenetic distance between donor and recipient. The results of these and previous experiments indicate that dipteran embryos contain localized RNP particles acting as anterior determinants. In Chironomus, the activity of these particles seems to depend on the integrity of polyadenylated RNA of about 250 to 500 nt length.

Abdomen

Potentiation by the lithium ion of morphogenetic responses to a Xenopus inducing factor.

We have cultured explants of Xenopus blastular animal cap tissue from embryos that had received an earlier treatment with LiCl and from their untreated siblings, in various concentrations of XTC-cell-derived mesoderm-inducing factor (XTC-MIF, Smith, 1987; Smith et al. 1988). The pretreatment with lithium that we used transforms later morphogenesis in the whole embryo to give radialized body forms with anterior/dorsal levels of structure grossly over-represented. In addition, animal caps from 'Li+' embryos were allowed to develop without exposure to in vitro MIF (Li+ controls) and compared with normal uninduced control explants, and explants were made from normal early blastulae but given various initial treatments with LiCl in culture. The results confirm that the lithium ion itself will not induce mesoderm in competent, animal cap tissue of Xenopus. It does, however, enhance the responsiveness of this tissue to XTC-MIF, in a way that parallels its recently reported effect in the case of another mesoderm inducer of different character, bFGF (Slack et al. 1988). The effects observed are sufficient to imply that the altered body pattern that follows lithium treatment, in whole embryos, could be caused by modulation of the responses to an unaltered pattern of in situ inductive stimuli. We also observe evidence that appreciable inductive signals reach animal pole tissue beyond the limits of mesoderm formation in normal development. Relatively low concentrations of MIF prevent the development of an epidermis-specific marker in dissociated blastular animal cap cells (Symes et al. 1988). When such experiments are repeated in relation to the lithium pretreatment of embryos, such treatment is seen to have sensitized the cell population, so that the MIF concentration range that assures complete suppression of the marker is reduced. The results are discussed in relation to induction considered as pattern formation.

Animals

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals

Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.

Animals

[Association of lichen planus and discoid lupus erythematosus. A clinical and histopathological study of 2 cases].

Two patients showing features of both lichen planus and lupus erythematosus are described: reticular whitish patches in the oral mucosa coexisting with chronic, partly atrophic LED-like skin lesions located on the face were present in both of them. The histological, histochemical and immunopathological findings allowed to diagnose a "LP-LE coexistence" more than a mixed LP-LE disease. The clinical, histological and immunological relationships between LP and LE are discussed and it is suggested that the pathogenesis of the coexistence of the two diseases could be related to a common pathophysiological pathway. It might be that LP and LE are due to a single aetiological agent (e.g. a virus) interacting with different genetic backgrounds to cause LE in some, LP in others and an intermediate disease in a small group of patients. The histopathological and immunopathological features that distinguish LP from LE are the concentration of lymphocytes in areas of keratinocyte damage, the different colloid bodies patterns and the direct IF findings. The Authors conclude that further studies should be performed on "LP-LE coexistence".

Adult

[Urinary incontinence and prolapse. Medical treatment and functional treatment].

Urinary continence implies that the variations of the vesical pressure does not exceed the capacities of the cervico-urethral closure system. The aim of the various methods of treatment is to have a beneficial action on those two parameters: drug therapy will mainly reduce the intra-vesical pressure (parasympatholytics...) and also improve the urethral tone (alpha-adrenergics...), or have a mixed effect on both systems (tricyclic antidepressants, oestrogens...). The side effects are often numerous due to the impact on the vegetative or neuromuscular system. The re-education is complemented by: local and general kinesitherapy, sensorial retrocontrol, associated or not to electrotherapy. Motivation and active participation of the patient are essential. The indications covers all the various pathologies (perineal insufficiency, defects in the body pattern, prolapse, sphincteral insufficiency, transmission problems, vesical instability, urethral instability) and concerns patients of all age groups.

Biofeedback, Psychology

Stature and body weight growth patterns from longitudinal data of Japanese children born during World War II.

Stature and body weight data of 100 boys and 100 girls from 7 to 17 years of age in Shimodate City who were born during World War II were longitudinally analyzed. The children were significantly smaller and lighter throughout their growth period than those born 11 years after the end of the war. The correlation coefficient between statures at each age and at age 17 showed a gradual increase with increasing age, while that between statures at each age and at age 7 decreased with age. However, a drop in the correlation coefficient was found during puberty, at age 11 for girls and at age 13 for boys. Comparing the normalized distance from mean values of stature and body weight at age 7, at puberty, and at age 17, only 51% of the children continued to be in the same relative position for both height and weight, 6% of boys and 4% of girls showing a decreasing pattern for both and 4% of boys and 7% of girls showing an increasing pattern for both. Thus, about 60% of the children of either sex presented parallel stature and body weight growth patterns for ages from 7 to 17.

Adolescent

Insulin sensitivity, glucose effectiveness, and body fat distribution pattern in nondiabetic offspring of patients with NIDDM.

OBJECTIVE: To determine the relationship of insulin sensitivity (SI), glucose effectiveness (glucose-dependent glucose transport [SG]), and body fat distribution patterns in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Ten glucose-tolerant offspring of patients with NIDDM and 10 age-, sex-, and weight-matched healthy control subjects without family history of diabetes were studied with the minimal model method of Bergman et al. Body fat composition and distribution pattern were assessed by the bioelectrical impedance analyzer and waist-hip circumference ratios (WHR), respectively, in each subject. RESULTS: Mean fasting serum glucose (4.39 +/- 0.17 vs. 3.94 +/- 0.17 mM) and postglucose peak (18.50 +/- 1.50 vs. 13.20 +/- 1.06 mM) levels were significantly greater (P less than 0.05) in the offspring than in the control subjects. Mean fasting serum insulin levels were slightly greater but not significantly different in the offspring versus control subjects (64 +/- 14 vs. 29 +/- 7 pM). After intravenous stimulation with glucose and tolbutamide, the mean serum insulin rose to significantly greater (P less than 0.05) levels at t = 5 and 25 min in the offspring compared with the control subjects. Mean SI was significantly reduced by 45% in the offspring compared with the control subjects (4.77 +/- 0.67 vs. 8.37 +/- 1.24 x 10(-4) min-1.mU-1.L-1). However, SG was not different in the offspring versus control subjects (1.92 +/- 0.12 vs. 2.10 +/- 0.17 x 10(-2) min-1). SI correlated significantly and inversely with the percentage of body fat mass (r = -0.580, P less than 0.05) but not with the WHR (r = -0.019) in the offspring. We found a negative association between SI and basal serum insulin (r = -0.798, P less than 0.01) but not with the poststimulation incremental insulin responses in the offspring. Family history of diabetes independently accounted for at least 27% of variance in the SI in our subjects. CONCLUSIONS: Our study confirmed that insulin insensitivity but not a reduced glucose effectiveness exists in young glucose-tolerant offspring of patients with NIDDM. The reduced S1 appears to be causally related to the total body fat content and may be a familial and/or genetic trait in the offspring.

Adipose Tissue

Manometric patterns using esophageal body and lower sphincter characteristics. Findings in 1013 patients.

In order to determine the actual spectrum of abnormal esophageal motility, manometric patterns in 1013 consecutive tracings were established using a classification method that employs esophageal body and lower esophageal sphincter (LES) characteristics. Peristaltic performance and contraction wave parameters were measured in the esophageal body; basal pressure and relaxation were included for the LES. Nine hundred thirty (92%) of the tracings could be completely classified, and 33 different patterns were observed (915 occurring at a rate greater than 1%). Abnormalities were most common in contraction wave parameters (661 tracings, 65%), and least common in LES relaxation (105 tracings, 10%). Patterns most typical of achalasia and diffuse esophageal spasm were found in 6.4% and 5.0% of tracings, respectively. Statistical analysis of the patterns demonstrated that significant bidirectional predictive associations between categories were restricted to features representing pathology-based motor disorders (ie, achalasia and "scleroderma-esophagus"). This systematic classification method is capable of recognizing and cataloging common findings of motor dysfunction in the esophageal body and LES as well as uncommon patterns representing traditional motility disorders. Our findings provide reference data for clinical esophageal manometry.

Esophageal Motility Disorders

A basis for determining body surface potential patterns attributable to single-site coronary arterial occlusion.

The authors focus on computational separation of the individual patterns of occlusion of the major segments of the right coronary artery. The raw patterns of occlusion throughout 15 standard subdivisions of the coronary arterial tree and body surface isoarea maps for 8 consecutive 10-msec intervals of QRS were examined in 200 patients with known coronary artery disease. Mean patterns of occlusion and of potential distribution were formed into 15 groups according to which patients showed greater than or equal to 90% occlusion of the respective segments. By diagonalization of the occlusion matrix, individual potential map patterns were obtained to represent the effect of isolated occlusion of each segment. While these patterns appeared consistent with the known anatomy of ventricular myocardial perfusion, further correlative study will be needed. The authors suggest that the use of such prototypical patterns of single-site obstruction may be helpful in forming and assessing recognition patterns in the clinical setting of multiple-site, multiple-vessel disease.

Coronary Disease

Influence of direction of body weight change on pattern of gonadotropin secretion in ovariectomized beef heifers of equivalent body weight.

Our hypothesis was that alterations in pattern of gonadotropin secretion induced by level of dietary energy intake are dependent on direction of BW change. Beef heifers were assigned to one of two treatments 21 d after ovariectomy: 1) increasing followed by decreasing BW (I-D; n = 9) or 2) decreasing followed by increasing BW (D-I; n = 9). Heifers assigned to the I-D treatment received 15.4 Mcal ME/d (HE) from wk 0 to 8 followed by 4.3 Mcal ME/d (LE) from wk 9 to 16. Heifers assigned to the D-I treatment received the LE diet for the initial 8 wk followed by the HE diet for the subsequent 8 wk. At 2-wk intervals blood samples were collected at 10-min intervals for 11 h to determine the pattern of secretion and(or) concentration of gonadotropins in circulation (LH and FSH) and pituitary responsiveness to administration of 750 ng and 50 micrograms of LHRH. Frequency of LH pulses increased (P less than .05) in a quadratic fashion with increasing ADG in heifers in both treatment groups. Amplitude of LH pulses decreased (P less than .05) in a linear fashion with increasing ADG in heifers in both treatment groups and magnitude of this decline was greater (P less than .05) in heifers receiving the D-I treatment. Amplitude of response to 750 ng of LHRH decreased (P less than .05) in a linear fashion with increasing ADG in heifers receiving the D-I treatment but was unrelated to changes in ADG (P greater than .05) in heifers receiving the I-D treatment. When heifers in both treatment groups attained similar BW (P greater than .05; wk 14), amplitude of LH pulses, responsiveness to 750 ng of LHRH and mean concentration of FSH in serum were higher (P less than .05) in heifers receiving the I-D than in heifers receiving the D-I treatment. Thus, we accept the hypothesis that alterations in pattern of gonadotropin secretion in heifers fed diets with a low energy content are dependent on direction of BW change.

Animals

Body fat distribution patterns and blood pressure in black and white women.

The prevalence of obesity and being overweight and the distribution of body fat in relation to blood pressure were assessed in a college population of 181 black and white US women and 124 black Nigerian women. The mean ages ranged from 18.6 to 22.4 years. Twenty-nine percent of black US women were overweight and 12.9% were obese; whereas 13.6% of white US women were overweight and 2.3% were obese. Only 18.6% of Nigerians were overweight and 1.6% were obese. More upper body fat was found among the black US women and Nigerians than among white US women. There was no significant correlation between body fat distribution and blood pressure among Nigerians. In general, among US blacks and whites, there were positive associations among body mass index, waist-hip girth measurements, and blood pressure, particularly for systolic blood pressure.

Adipose Tissue

Two discharge patterns of carotid body chemoreceptors in the goat.

Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer.

Action Potentials