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Patterns of body weight change in rats following neonatal hormone manipulation: a "critical period" for androgen-induced growth increases.

The development of sexual behaviour and gonadal function is largely determined by the early postnatal hormone environment in the rat; testosterone propionate (TP) treatment in the neonatal female will stimulate development of predominantly masculine functional characteristics. On the other hand, removal of the testes from neonatal males results in feminization of these characteristics. It has been shown that an optimal neonatal steroid hormone environment is also essential for normal growth. We now report the effects of different doses of TP (10, 30, 90, or 270 mug) given on postnatal days 2, 3, 4, or 5 on growth as measured primarily by body weight. Only treatment in the 30-270 mug range on days 2 or 3 was effective in causing significant growth changes, however, these same doses caused sterility and impaired female sexual behaviour when given on days 4 or 5. Therefore, there appears to be a "critical period" before the fourth postnatal day when TP can affect processes leading to increased growth. Removal of the neonatal testes retards growth to the levels of the androgenized females. The ovaries of the female TP treated rats still have a restraining influence on growth since their removal produces an increment in body weight similar to, though not as great as, that of the normal ovariectomized rat. These findings suggest that neonatal TP administration may possibly reduce the responsiveness of rats to the growth depressing effect of ovarian steroids by action at a site functionally different from that producing sterility and impaired sexual behaviour.

Age Factors

Influence of feeding Aspergillus oryzae fermentation extract on the milk yields, eating patterns, and body temperatures of lactating cows.

Trials were conducted to evaluate effects of a fermentation extract of Aspergillus oryzae (AO) on milk production and composition, diet digestibility, and rectal temperature changes in lactating dairy cows. Treatments were incorporated as a top dressing at the morning feeding and consisted of control (90 g/d of ground sorghum) or AO (3 g of culture + 87 g of ground sorghum daily). Twenty-four mid-lactation Holstein cows were paired for production in Lactation Trial 1 (LT-1). In Lactation Trial 2 (LT-2), 46 cows (20 primiparous and 26 multiparous) in early lactation were used. Trials lasted 12 wk. In LT-1, AO supplementation increased milk yields only at 2 (P less than .05) and 8 wk (P less than .10) of treatment. Rectal temperatures were lower (P less than .05) for cows fed AO for 4 of 10 readings made during summer. Supplementation of AO culture in LT-2 (early lactation cows) increased milk production and feed efficiency (P less than .05). Inner ear temperatures tended to be lower (P less than .11) for cows fed AO. Digestion trials, conducted at the end of lactation trials, used Cr2O3 as an indigestible marker. In Digestion Trial 1, digestibilities were not significantly (P greater than .10) affected by AO supplementation. However, in Digestion Trial 2, AO increased (P less than .05) digestibilities of DM, OM, CP, NDF, and ADF. Length and number of meals were not affected (P greater than .10) by feeding AO. In summary, milk yields, efficiency of milk production, and nutrient digestibilities were higher for early lactation cows fed a high-concentrate diet supplemented with 3 g of AO/d. Mid-lactation cows fed a lower-energy diet were less responsive to AO than early lactation cows, though similar trends were shown.

Analysis of Variance

[Correlation between lipid pattern and body mass index in obesity].

Lipid plasma levels were measured in a group of 519 obese subjects, aged 7-66 years, divided according to age, sex and BMI. Lipidemia and total cholesterolemia increased both with age and BMI, irrespective of sex; LDL and VLDL increased in relation to age and, with less evident differences, to BMI. Triglycerides increased in the age bracket from adolescent to adult, especially in males, whereas their increase in relation to BMI showed no difference between the sexes. Chylomicron plasma levels remained steady both in relation to age and BMI.

Adolescent

Time of death of CNS tumor-bearing rats can be reliably predicted by body weight-loss patterns.

A request by the Institutional Animal Care and Use Committee for an alternative to death as an end point in a cancer research project using a rat brain 9L tumor cell model led to a search for reliable criteria for predicting time of death in this type of experiment. These experiments evaluated the therapeutic effectiveness of radiation alone, continuous intracerebral infusions of 5-iodo-2-deoxyuridine (IUDR) alone, and a combination of both therapies. We found that a characteristic pattern of body weight changes occurs after injection of 9L tumor cells into the brain ventricles or parenchyma. The initial phase was characterized by a loss of body weight which appeared to be related to surgery and, in the irradiated groups, to the subsequent doses of radiation under anesthesia on days 4, 6, and 7. After this initial phase (phase 1), a second period of weight change (phase 2) which was characterized by an overall gain of body weight interrupted temporarily in 76 out of the 149 rats by reversible episodes of weight loss of 1 to 5 days duration. The length of this phase 2 weight gain period was significantly extended by XRT-IUDR treatment in the rats with intraparenchymal tumors. The third and final phase consisted of a period of irreversible weight loss which may be related to cachexia. The third phase was similar in duration for control, XRT, IUDR and XRT-IUDR groups of rats and had a mean length of 9.8 +/- 0.27 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Drosophila wingless generates cell type diversity among engrailed expressing cells.

During embryogenesis, body pattern is established in a stepwise process. After specification of the body axis, the embryo is subdivided into smaller units. Within these units, a diverse array of cell types is then generated. The subdivisions of the Drosophila embryo, called parasegments, are defined by the interface between cells expressing the homeoprotein Engrailed and cells expressing the secreted protein Wingless. We have examined the generation of cell-type diversity within parasegments by focusing on the choice of cell fate made by the engrailed (en)-expressing cells. These cells differentiate as one of two alternative cell types. We report here that this choice is mediated by wingless (wg), in a function distinct from its early role maintaining en expression. Thus, en cells exhibit different responses to the wg signal at different developmental stages. Early wg input stabilizes the subdivision of the body axis by maintaining en expression, whereas later input generates cell-type diversity.

Animals

Two gap genes mediate maternal terminal pattern information in Drosophila.

In Drosophila three maternal pattern organizing activities, the anterior, the posterior, and the terminal, establish the anterior-posterior body pattern of the embryo by initiating the spatially restricted activities of the gap class of zygotic segmentation genes. The activities of tailless (tll) and the newly identified gap gene huckebein (hkb) are specifically involved in mediating the maternal terminal information at the posterior end of the blastoderm embryo.

Animals

Thermographical investigation of decubitus ulcers.

1. Posterior body reference thermograms indicate that in general a similar thermal body pattern of humans does exist. 2. The buttocks, hips, and thighs of a nude subject are thermally cool regions, possibly indicating poor vascular circulation and/or large fat concentrations. 3. Thermograms of the same anatomical area on the same subject under controlled environmental conditions are thermally similar. 4. The scapular region is from 1 to 2 deg F hotter than the sacral region for subjects reclining on Mylar. 5. The 1 deg temperature differential thermograms and the reference thermogram while the subject is on Mylar, in many ways, denote the geometrical shape of the underlying bone structure, especially the bones of the scapulae and sacrum. 6. On the degree temperatue differential thermograms, the anatomical regions most accused of being decubitus ulcer prone are the regions of highest temperatures: the scapulae, sacrum, elbows, and calves. 7. During reactive hyperemia, the visible red flare over the sacrum and coccyx becomes very intense in the first few minutes and then gradually diminishes. The thermal flare persists longer than the visible flare. The extended duration of the thermal flare over the visible red flare is attributed to a continued local elevated metabolic tissue rate caused by the previous engorgement of blood. 8. The thermal mottling seen in the first minute after releasing the load is believed to have been caused by the rapid infusion of blood and the dilation of affected vessels responsible for making up the blood flow debt which occurred during the period of ischemia. 9. A posterior body heating effect noticed immediately after the subject left the Mylar film has been attributed to the insulative qualities of the film. The cooling effect is more difficult to explain, but it is thought that the higher than average room temperature caused an increased evaporative cooling rate response of the two subjects either before getting off the film or immediately after getting off and therefore reduced the temperature of the skin. 10. The maximum reactive hyperemic temperature difference, the difference between the initial standing reference thermogram and the maximum flare temperature observed during tissue hyperemia, may be as high as 12 deg F. 11. Males on the average have larger flare patterns than females, 5.7 in.2 and 4.7 in.2, respectively. The flare areas were computed from thermograms taken 2 to 3 minutes after off-loading of tissue. 12. With the average distance from the buttock's fold to the highest and lowest thermal flare indication being lower for females (3.2 and 5.9) than for males (3.8 and 6.4), a relationship between the site or decubitus ulcer formation and the pelvic bone structure of the sexes may well exist. 13. No two thermal flare patterns are similar either in size or in shape. Thermal flare patterns occur along the centerline of the body at the sacrum and coccyx level. 14...

Adolescent

From egg to pole cells: ultrastructural aspects of early cleavage and germ cell determination in insects.

Insect eggs are giant and very complex cells covered by an extremely resistant shell. Both the egg cell and surrounding eggshell express anteroposterior and ventrodorsal polarity. The molecular and cytoplasmic organization of both axes originates during oogenesis and leads to the production of an ooplasmic system which consists of euplasm and deutoplasm (yolk) and contains a nucleus as well as extranuclear determinants of maternal origin. Both are part of the store of information for early embryogenesis. In addition, the deutoplasm serves as raw material and early nutrient supply for building the embryo. The insect egg cell, which is arrested in the first maturation division when released from the ovary during oviposition, will be activated by different stimuli among different species to complete meiosis and start embryogenesis. The zygote nucleus undergoes a number of synchronous mitotic divisions leading to cleavage energids which initially form a syncytial blastoderm and subsequently the cellular blastoderm. In many insects, prior to blastoderm formation, polar granules (or oosome material) are incorporated in a single cell or a small number of cells which bud off at the posterior pole. These so called pole cells give rise to the primordial germ cells. Therefore, polar granules or the oosome material mark the germ line, and while structural counterparts of determinants of body pattern formation have so far not been found, the polar granules or oosome serve as an autonomous ooplasmic determinant for the pole or germ cells. Anteroposterior body polarity can arise independent of the germ plasm.

Animals

Regressive language in severe head injury.

In a follow-up study of 50 patients with severe head injuries three patients had echolalia. One patient with initially global aphasia had echolalia for some weeks when he started talking. Another patient with severe diffuse brain damage, dementia, and emotional regression had echolalia. The dysfunction was considered a detour performance. In the third patient echolalia and palilalia were details in a total pattern of regression lasting for months. The patient, who had extensive frontal atrophy secondary to a very severe head trauma, presented an extreme state of regression returning to a foetal-body pattern and behaving like a baby.

Adolescent

The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos.

A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains. This paper deals with one of these genes, Xlim-1. Xlim-1 mRNA is found at low abundance in the unfertilized egg, has a major expression phase at the gastrula stage, decreases, and rises again during the tadpole stage. In adult tissues the brain shows the highest abundance, by far, of Xlim-1 mRNA. The maternal and late expression phases of the Xlim-1 gene suggest that it has multiple functions at different stages of the Xenopus life cycle. In the gastrula embryo, Xlim-1 mRNA is localized in the dorsal lip and the dorsal mesoderm, that is, in the region of Spemann's organizer. Explant experiments showed that Xlim-1 mRNA is induced by the mesoderm-inducer activin A and by retinoic acid, which is not a mesoderm inducer but affects patterning during Xenopus embryogenesis; application of activin A and retinoic acid together results in synergistic induction. The structure, inducibility, and localized expression in the organizer of the Xlim-1 gene suggest that it has a role in establishing body pattern during gastrulation.

Activins

cactus, a maternal gene required for proper formation of the dorsoventral morphogen gradient in Drosophila embryos.

The dorsoventral pattern of the Drosophila embryo is mediated by a gradient of nuclear localization of the dorsal protein which acts as a morphogen. Establishment of the nuclear concentration gradient of dorsal protein requires the activities of the 10 maternal 'dorsal group' genes whose function results in the positive regulation of the nuclear uptake of the dorsal protein. Here we show that in contrast to the dorsal group genes, the maternal gene cactus acts as a negative regulator of the nuclear localization of the dorsal protein. While loss of function mutations of any of the dorsal group genes lead to dorsalized embryos, loss of cactus function results in a ventralization of the body pattern. Progressive loss of maternal cactus activity causes progressive loss of dorsal pattern elements accompanied by the expansion of ventrolateral and ventral anlagen. However, embryos still retain dorsoventral polarity, even if derived from germline clones using the strongest available, zygotic lethal cactus alleles. In contrast to the loss-of-function alleles, gain-of-function alleles of cactus cause a dorsalization of the embryonic pattern. Genetic studies indicate that they are not overproducers of normal activity, but rather synthesize products with altered function. Epistatic relationships of cactus with dorsal group genes were investigated by double mutant analysis. The dorsalized phenotype of the dorsal mutation is unchanged upon loss of cactus activity. This result implies that cactus acts via dorsal and has no independent morphogen function. In all other dorsal group mutant backgrounds, reduction of cactus function leads to embryos that express ventrolateral pattern elements and have increased nuclear uptake of the dorsal protein at all positions along the dorsoventral axis. Thus, the cactus gene product can prevent nuclear transport of dorsal protein in the absence of function of the dorsal group genes. Genetic and cytoplasmic transplantation studies suggest that the cactus product is evenly distributed along the dorsoventral axis. Thus the inhibitory function that cactus product exerts on the nuclear transport of the dorsal protein appears to be antagonized on the ventral side. We discuss models of how the action of the dorsal group genes might counteract the cactus function ventrally.

Alleles

The role of growth factors in embryonic induction in Xenopus laevis.

Establishment of the body pattern in all animals, and especially in vertebrate embryos, depends on cell interactions. During the cleavage and blastula stages in amphibians, signal(s) from the vegetal region induce the equatorial region to become mesoderm. Two types of peptide growth factors have been shown by explant culture experiments to be active in mesoderm induction. First, there are several isoforms of fibroblast growth factor (FGF), including aFGF, bFGF, and hst/kFGF. FGF induces ventral, but not the most dorsal, levels of mesodermal tissue; bFGF and its mRNA, and an FGF receptor and its mRNA, are present in the embryo. Thus, FGF probably has a role in mesoderm induction, but is unlikely to be the sole inducing agent in vivo. Second, members of the transforming growth factor-beta (TGF-beta) family. TGF-beta 2 and TGF-beta 3 are active in induction, but the most powerful inducing factors are the distant relatives of TGF-beta named activin A and activin B, which are capable of inducing all types of mesoderm. An important question relates to the establishment of polarity during the induction of mesoderm. While all regions of the animal hemisphere of frog embryos are competent to respond to activins by mesoderm differentiation, only explants that include cells close to the equator form structures with some organization along dorsoventral and anteroposterior axes. These observations suggest that cells in the blastula animal hemisphere are already polarized to some extent, although inducers are required to make this polarity explicit.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

oskar mRNA is localized to the posterior pole of the Drosophila oocyte.

Mutants of the maternal posterior-group genes of Drosophila lack posterior body pattern elements and germ cells, both of which form through the action of determinants localized to the posterior pole of the oocyte. We report that transcripts of one of these genes, oskar, become localized to the posterior pole of oocytes shortly after the oocyte begins to differentiate visibly. Analysis of various posterior-group mutants reveals that localization of oskar mRNA is an early step in the posterior localization pathway. In addition, we find that nonsense oskar mutations disrupt osk mRNA localization, while missense oskar mutations do not.

Amino Acid Sequence

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals

The Drosophila segmentation gene runt has an extended cis-regulatory region that is required for vital expression at other stages of development.

The Drosophila runt gene functions in several developmental pathways during embryogenesis. This gene was initially characterized due to the pivotal role that it plays in the genetic regulatory network that establishes the segmented body pattern. Recently it was found that this X-chromosome-linked gene is one of several dosage-sensitive, X-linked components that is involved in activating the Sex-lethal gene in blastoderm stage female embryos. Finally, this gene is also extensively re-expressed in later stages of embryogenesis in the developing nervous system where it plays an important role in the development of specific neural lineages. We have initiated an analysis of the runt cis-regulatory region in order to investigate runt's roles in these (and other) developmental pathways. Analysis of both the function and the expression patterns of runt genes with truncated cis-regulatory regions indicates that there are multiple elements that make quantitative contributions to runt regulation during segmentation. We find that sequences that are more than 8.5 kb upstream of the runt promoter are necessary for normal expression during the post-blastoderm stages of embryogenesis. Genetic experiments indicate that the post-blastoderm expression of runt is vital to the organism.

Alleles

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

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

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