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PubMed2002

Microvolt T wave alternans inducibility in normal newborn puppies: effects of development.

INTRODUCTION: The cause of sudden infant death syndrome is unknown, but increased cardiac vulnerability due to repolarization instability may be a contributing factor. The QT interval normally is long at birth and increases further during the first few postnatal months. Although excessive QT intervals indicate increased cardiac vulnerability in the long QT syndrome, the impact of less pronounced QT prolongation during this developmental period is unclear. In adults and older children, the ease of inducing microvolt-level T wave alternans (TWA) is used as a measure of repolarization instability and arrhythmia vulnerability. The aim of this study was to determine if TWA is inducible in normal newborn puppies. METHODS AND RESULTS: Atrial pacing was performed in 15 anesthetized beagle puppies 7 to 35 days old. The pacing drive cycle length was systematically decreased in 20-msec steps from baseline until AV conduction blocked. Pacing was performed for 8 minutes at each cycle length. Three-lead ECGs were recorded continuously during the last 5 minutes of pacing at each cycle length. The recordings were analyzed off-line for the presence of microvolt-level TWA using a sensitive spectral analysis technique. Microvolt-level TWA was present in all puppies. TWA was not present at baseline but developed and increased in amplitude as heart rate increased. The threshold heart rate for TWA did not correlate with age. However, due to age-dependent changes in baseline heart rate, the 7- to 14-day-old animals needed a 50% to 78% increase in heart rate to reach threshold heart rate, whereas the oldest animals needed only a 5% to 25% increase. CONCLUSION: These data suggest that developmentally dependent dynamic repolarization instability exists in puppies as manifest by the inducibility of TWA.

Age Factors↗
PubMed1989

Regulation of neuronal oxytocin mRNA by ovarian steroids in the mature and developing hypothalamus.

We have examined the changes in neuronal expression of oxytocin mRNA in the perinatal and mature female rat as a function of endogenous gonadal steroids. Northern blot analysis demonstrated a significant developmental increase in the abundance of oxytocin mRNA in the female brain concomitant with puberty. Ovariectomy of adult females decreased total brain oxytocin mRNA to significantly lower levels. In contrast, lactating mothers had increased levels of neuronal oxytocin mRNA. In situ hybridization analysis of neuronal oxytocin mRNA in adolescent, mature virgin, and ovariectomized virgin female brains demonstrated that the location and number of neurons expressing oxytocin mRNA was unchanged and that total brain oxytocin mRNA differences were attributable to amounts expressed per neuron. Differences in mRNA abundance were noted in oxytocin neurons throughout the hypothalamus, including those known to project as magnocellular neurons to the neurohypophysis and those of parvocellular origin thought to make wholly intracerebral connections. This developmental and dynamic regulation of oxytocin mRNA levels during gonadal maturation may coordinate the peripheral and central effects of this peptide on the reproductive biology of the female rat.

Aging↗
PubMed1970

Origin, development, and nature of intranuclear rodlets and associated bodies in chicken sympathetic neurons.

Correlative data are presented here on the developmental history, dynamics, histochemistry, and fine structure of intranuclear rodlets in chicken sympathetic neurons from in vivo material and long-term organized tissue cultures. The rodlets consist of bundles of approximately 70 +/- 10 A proteinaceous filaments closely associated with approximately 0.4-0.8 micro spheroidal, granulofibrillar (gf) bodies of a related nature. These bodies are already present in the developing embryo a week or more in advance of the rodlets. In early formative stages rodlets consist of small clusters of aligned filaments contiguous with the gf-bodies. As neuronal differentiation progresses these filaments increase in number and become organized into well-ordered polyhedral arrays. Time-lapse cinemicrography reveals transient changes in rodlet contour associated with intrinsic factors, changes in form and position of the nucleolus with respect to the rodlet, and activity of the gf-bodies. With the electron microscope filaments may be seen extending between the nucleolus, gf-bodies, and rodlets; nucleoli display circumscribed regions with fine structural features and staining reactions reminiscent of those of gf-bodies, We suggest that the latter may be derivatives of the nucleolus and that the two may act together in the assemblage and functional dynamics of the rodlet. The egress of rodlet filaments into the cytoplasm raises the possibility that these might represent a source of the cell's filamentous constituents.

Animals↗
PubMed2005

Classification using functional data analysis for temporal gene expression data.

MOTIVATION: Temporal gene expression profiles provide an important characterization of gene function, as biological systems are predominantly developmental and dynamic. We propose a method of classifying collections of temporal gene expression curves in which individual expression profiles are modeled as independent realizations of a stochastic process. The method uses a recently developed functional logistic regression tool based on functional principal components, aimed at classifying gene expression curves into known gene groups. The number of eigenfunctions in the classifier can be chosen by leave-one-out cross-validation with the aim of minimizing the classification error. RESULTS: We demonstrate that this methodology provides low-error-rate classification for both yeast cell-cycle gene expression profiles and Dictyostelium cell-type specific gene expression patterns. It also works well in simulations. We compare our functional principal components approach with a B-spline implementation of functional discriminant analysis for the yeast cell-cycle data and simulations. This indicates comparative advantages of our approach which uses fewer eigenfunctions/base functions. The proposed methodology is promising for the analysis of temporal gene expression data and beyond. AVAILABILITY: MATLAB programs are available upon request.

Algorithms↗
PubMed2004

Developmental changes in upper airway dynamics.

Normal children have a less collapsible upper airway in response to subatmospheric pressure administration (P(NEG)) during sleep than normal adults do, and this upper airway response appears to be modulated by the central ventilatory drive. Children have a greater ventilatory drive than adults. We, therefore, hypothesized that children have increased neuromotor activation of their pharyngeal airway during sleep compared with adults. As infants have few obstructive apneas during sleep, we hypothesized that infants would have an upper airway that was resistant to collapse. We, therefore, compared the upper airway pressure-flow (V) relationship during sleep between normal infants, prepubertal children, and adults. We evaluated the upper airway response to 1). intermittent, acute P(NEG) (infants, children, and adults), and 2). hypercapnia (children and adults). We found that adults had a more collapsible upper airway during sleep than either infants or children. The children exhibited a vigorous response to both P(NEG) and hypercapnia during sleep (P < 0.01), whereas adults had no significant change. Infants had an airway that was resistant to collapse and showed a very rapid response to P(NEG). We conclude that the upper airway is resistant to collapse during sleep in infants and children. Normal children have preservation of upper airway responses to P(NEG) and hypercapnia during sleep, whereas responses are diminished in adults. Infants appear to have a different pattern of upper airway activation than older children. We speculate that the pharyngeal airway responses present in normal children are a compensatory response for a relatively narrow upper airway.

Adolescent↗
PubMed1997

Neonatal hypoglycemia, Part I: Background and definition.

Hypoglycemia in the neonate remains a common problem. The association of low blood glucose concentrations and abnormal development has prompted extensive research into the anticipation, evaluation, and treatment of neonatal hypoglycemia. Glucose homeostasis in the fetus and neonate is a developmentally regulated dynamic process involving a number of intricate physiologic mechanisms. In addition, the determination of glucose concentrations is dependent upon both the type of tissue analyzed and the limitations of the specific method employed. The complexity of glucose metabolism makes it difficult to precisely define "normal" and "abnormal" glucose levels in preterm and term neonates.

Blood Glucose↗
PubMed1986

On transference: developmental and clinical considerations.

Following a short historical overview of the evolution of the concept of transference, the factors involved in this process are examined. The developmental or dynamic aspects of transference, that is, its illusory character defined by the "potential space" within which transference develops, and the importance of the holding environment at the early stages of therapy for an optimal development of transference are discussed. To understand resistances, Merton Gill's distinction of resistances to the awareness of the transference, and resistances to the resolution of the transference are particularly relevant. Finally, the concept of transference neurosis is focused upon. Detailed clinical vignettes are given to illustrate the points made. Although the clinical material is taken from sessions of patients in analysis the theoretical implications pertaining to the transference are equally applicable to the practice of psychoanalytic psychotherapy. It is in this spirit that throughout the paper the terms "therapeutic" and "analytic" are used interchangeably.

Defense Mechanisms↗
PubMed2005

Directed migration of positively selected thymocytes visualized in real time.

Development of many vertebrate tissues involves long-range cell migrations. In most cases, these migrations have been inferred from analysis of single time points and the migration process has not been directly observed and quantitated in real time. In the mammalian adult thymus, immature CD4+ CD8+ double-positive (DP) thymocytes are found in the outer cortex, whereas after T cell antigen receptor (TCR) repertoire selection, CD4+ CD8- and CD4- CD8+ single-positive (SP) thymocytes are found in the central medulla. Here we have used two-photon laser-scanning microscopy and quantitative analysis of four-dimensional cell migration data to investigate the movement of thymocytes through the cortex in real time within intact thymic lobes. We show that prior to positive selection, cortical thymocytes exhibit random walk migration. In contrast, positive selection is correlated with the appearance of a thymocyte population displaying rapid, directed migration toward the medulla. These studies provide our first glimpse into the dynamics of developmentally programmed, long-range cell migration in the mammalian thymus.

Animals↗
PubMed2000

Angiopoietin-2 is a site-specific factor in differentiation of mouse renal vasculature.

Angiopoietin-1 (Ang-1) stimulates endothelial and vascular network differentiation through the Tie-2 receptor tyrosine kinase, while Ang-2 modulates this activation in embryo and tumor growth. The nephrogenic pattern of Ang-2 was documented in a mouse strain that expresses the LacZ reporter gene driven by the Ang-2 promoter. Heterozygous animals were healthy with morphologically normal kidneys, and they were examined after X-gal staining. At embryonic days 10.5 (E10.5) and E12.0, transgene expression was absent in the mesonephros and metanephros. At E14.0, expression was noted in the metanephric artery and its major branches. At E19.0 and in neonatal kidneys, expression was maintained in larger renal artery branches, extending to arcuate and smaller cortical vessels. Histologically, transgene expression was located in multiple layers of vessel wall cells, extending further from the endothelium than alpha-smooth muscle actin. The mesangium of immature glomeruli also expressed LacZ. In the first 3 postnatal weeks, a new pattern became evident, with intense X-gal staining in the inner stripe of the outer medulla, where a subset of thin descending limbs of loops of Henle expressed the transgene. This dynamic and developmentally regulated pattern indicates that Ang-2 is an early marker of the renal pericyte and vascular smooth muscle lineage and is also an epithelial-derived growth factor. Because Tie-2 is widely expressed by differentiating renal endothelia, this study is consistent with the hypothesis that Ang-2 has roles in kidney vascular maturation.

Angiopoietin-2↗
PubMed2026

SET domain bifurcated histone lysine methyltransferase 1 regulates histone modification and DNA damage response during zygotic genome activation in pigs.

SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is a key epigenetic regulator that catalyzes histone H3 lysine 9 trimethylation (H3K9me3), a mark essential for transcriptional repression and heterochromatin formation. Here, we investigated the role of SETDB1 during zygotic genome activation (ZGA) in porcine embryos. SETDB1 knockdown (KD) was induced by microinjecting double-stranded RNA (dsRNA), and its impact on early embryonic development was evaluated. SETDB1 KD decreased H3K9me3 levels, markedly increased H3K9ac, and downregulated ZGA-associated genes. These epigenetic alterations were accompanied by impaired cleavage, reduced blastocyst formation, and a lower total cell number. Upon etoposide-induced DNA double-strand breaks, SETDB1 KD embryos showed reduced expression of key DNA repair proteins, failed to efficiently restore DNA integrity, and exhibited increased apoptosis, indicating a compromised DNA damage response and repair process. SETDB1 KD also reduced HDAC3 expression, suggesting that SETDB1 may regulate HDAC3 to maintain histone acetylation balance. Consistently, HDAC3 inhibition increased H3K9ac, decreased H3K9me3, and reduced SETDB1 protein levels, supporting a reciprocal regulatory relationship. Together, these findings indicate that SETDB1 is important for porcine embryonic development by coordinating histone modifications and safeguarding genomic integrity during ZGA, and they suggest that the interplay between SETDB1 and HDAC3 constitutes a potentially important epigenetic axis for proper histone modification dynamics and developmental competence.

Animals↗
PubMed2001

[Stability in development and variability in morphological signs in a natural population of Drosophila melanogaster: seasonal dynamics in 1999].

Seasonal dynamics of developmental stability and variability of morphological traits was examined in a natural population of Drosophila melanogaster in order to compare these two parameters as indicators of temperature stress. Morphometric (thorax length and wing length) and meristic (number of sternopelural and orbital bristles) were studied. Variability was measured as the coefficient of variation. Stability of development was estimated as fluctuating asymmetry (FA) of bilateral traits. Thorax length and wing length did not exhibit consistent seasonal trends whereas wing loading significantly decreased. Significant seasonal changes in FA were not detected in any trait examined. Two traits showed reduced variation in autumn. The use of FA as an indicator of ecological stresses in insects is discussed on the basis of these results and the literature evidence.

Animals↗
PubMed1992

Eating disorders. A review and update.

Anorexia nervosa and bulimia nervosa are prevalent illnesses affecting between 1% and 10% of adolescent and college age women. Developmental, family dynamic, and biologic factors are all important in the cause of this disorder. Anorexia nervosa is diagnosed when a person refuses to maintain his or her body weight over a minimal normal weight for age and height, such as 15% below that expected, has an intense fear of gaining weight, has a disturbed body image, and, in women, has primary or secondary amenorrhea. A diagnosis of bulimia nervosa is made when a person has recurrent episodes of binge eating, a feeling of lack of control over behavior during binges, regular use of self-induced vomiting, laxatives, diuretics, strict dieting, or vigorous exercise to prevent weight gain, a minimum of 2 binge episodes a week for at least 3 months, and persistent overconcern with body shape and weight. Patients with eating disorders are usually secretive and often come to the attention of physicians only at the insistence of others. Practitioners also should be alert for medical complications including hypothermia, edema, hypotension, bradycardia, infertility, and osteoporosis in patients with anorexia nervosa and fluid or electrolyte imbalance, hyperamylasemia, gastritis, esophagitis, gastric dilation, edema, dental erosion, swollen parotid glands, and gingivitis in patients with bulimia nervosa. Treatment involves combining individual, behavioral, group, and family therapy with, possibly, psychopharmaceuticals. Primary care professionals are frequently the first to evaluate these patients, and their encouragement and support may help patients accept treatment. The treatment proceeds most smoothly if the primary care physician and psychiatrist work collaboratively with clear and frequent communication.

Adolescent↗
PubMed2003

The concentration of lipids, lipoproteins and apolipoproteins in cord blood serum of newborns in the course of intrauterine period.

The period of foetal life as the first stage in the individual development is very important for every man. This is a period in which the greatest dynamics of developmental changes and particularly great susceptibility to the influence of negative factors are observed. The exponent of the correct prenatal life of the foetus is the birth weight of a newborn, which defines the degree of biological maturity of the child and its ability to live in the course of the subsequent stages of individual life. Therefore, the aim of the present study was to check the influence of foetal life on some of the parameters of lipids metabolism in the cord blood serum in healthy newborns as well as the evaluation of the concentration of lipids, lipoproteins and apolipoproteins with relation to the birth weight and also the gestational age of the studied newborns. The study was carried out on 137 healthy newborns (63 boys and 74 girls). In all of the studied newborns concentration of triglycerides, total cholesterol, LDL-cholesterol, VLDL-cholesterol and HDL-cholesterol as well as of apolipoproteins (apo-Al, apo-B) in the cord blood serum sampled soon after birth was studied. In the cord blood serum of the LBW newborns higher values of triglycerides, total cholesterol, cholesterol in fraction VLDL and apolipoprotein B were confirmed as well as the tendency towards lower values of HDL-cholesterol, which is an unfavourable phenomenon from the point of the risk of arteriosclerosis. No statistically significant differences in the level of lipids, lipoproteins and apolipoproteins in cord blood serum of the studied newborns depending on their gestational age were confirmed. The results may suggest that the risk factors of cardiovascular disease may to great extent depend on the intrauterine development and low birth weight.

Apolipoproteins↗
PubMedDate not supplied

[Study of some characteristics of morphogenesis and germination of Pinus pallasiana D. Don. pollen].

Investigation of Pinus pallasiana D. Don. pollen morphogenesis in natural forest plantations of the southern slope of the Main ridge of Crimean mountains has been carried out. Some abnormalities of pollen grain and pollen tube formation in the course of pollen germination in vitro are described. The dynamics of developmental abnormalities of P. allasiana male gametophyte is characterized.

Germination↗
PubMed2006

[Dynamics of morphofunctional organization and developmental potential of mouse embryos in the state of "two-cell block in vitro"].

Vital observation in combination with electron microscopy and immunocytochemistry was used for studying structural organization and developmental potential of BALB/c mouse embryos after cleavage cessation at a two cell stage caused by the "two-cell block in vitro" phenomenon. Modification of structure and viability of embryos was followed for 2 days from the time of cleavage arrest. Several hours before cleavage arrest, changes in mitochondrian distribution were noticed in embryos, no other disturbances in structural organization of blastomeres being obvious. Embryos, whose development was arrested for 24 h, remained viable and demonstrated some morphological changes similar to those seen in normally developing embryos of the same age. Towards the end of a 48 h block period some embryos died, the surviving embryos remained morphologically intact and metabolically active. At the same time, the nuclei of the latter frequently displayed chromatin condensation near the nuclear membrane, which is similar to the pattern of chromatin reorganization in the nuclei of early apoptotic cells. Our results support a concept on the "two-cell block in vitro" phenomenon as a specific functional state of embryos, and well compare with data on a partial realization by blocked embryos of the developmental program.

Animals↗
PubMed1987

Characterization of an inhibitor of neuronal plasminogen activator released by heart cells.

A basic understanding of growth cone dynamics and developmental events involving growth cones requires an understanding of the function and regulation of molecules associated with and released by growth cones. Rat sympathetic neurons in culture release a urokinase-like plasminogen activator from their distal processes and/or growth cones (Pittman, 1985a). When sympathetic neurons are grown in cocultures with heart cells, however, plasminogen activator activity is not detected. The absence of plasminogen activator activity in cocultures of sympathetic neurons and heart cells appears to be due to the release of an inhibitor of plasminogen activator by heart cells. This inhibitor has a molecular weight of approximately 50 kDa in the presence of SDS and apparent molecular weights of approximately 50 and greater than 2000 kDa under native conditions. A significant fraction of the large-molecular-weight form of the inhibitor is converted to the smaller form following treatment with heparinase. Extremely stable complexes of 68 and 80 kDa are formed between the heart inhibitor and the plasminogen activator, urokinase, such that the complexes withstand boiling in SDS/mercaptoethanol. The data are consistent with the formation of an 80 kDa urokinase-inhibitor complex in the presence of heparan sulfate proteoglycan and a 68 kDa complex in the absence of heparan sulfate proteoglycan. A highly purified preparation of the heart inhibitor produces a 2- to 3-fold increase in neurite outgrowth from sympathetic neurons. These data indicate that the activity of the plasminogen activator released by sympathetic neurons can be regulated by a normal target tissue and that this regulation may result in increased neurite outgrowth from the neurons.

Animals↗
PubMed1983

Pathological identification in twins.

In summary, in addition to the cultural, parental, developmental, and dynamic factors which support mutual identification and/or failure of separation between twins, it is my thesis that the basic early identifications between twins rely heavily on relatively conflict-free perceptual modes (visual, auditory, kinesthetic, etc.) quite different from the conflict-laden drive modes we usually think of when considering identification. Furthermore, identification based on perceptual modes, which are relatively free of conflict in early development, become extremely difficult to analyze, as analytic progress depends on conflict.

Adult↗