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Age-dependent changes in the proliferative response of S-100 protein-positive glial cells to injury in the rat brain.

A mechanical injury was inflicted to the left cerebral hemisphere in rats of four age groups: newborns, 6, 14 and 30 days old. The injury was followed by [3H]thymidine injections at different time intervals. Brain sections were immunostained for S-100 protein and subjected to autoradiography. During microscopic observations of the injury region, locations and numbers of the autoradiographically labeled astrocytes expressing S-100 protein were recorded. On the basis of the observations, injury-induced changes in the total number of proliferating astrocytes, as well as in their distribution, were analysed quantitatively. In rats injured neonatally, as well as those injured on postnatal days 6 and 14, the reactive increase in the number of proliferating astrocytes began on the first post-traumatic day. In 30-day-old rats the increase was slower and appeared on day 2. The maximal increase in the astrocyte proliferative activity occurred in 6-day-old rats as early as day 1 after injury and was about eight times higher than that recorded in newborns, and nearly twice as high as that recorded in brains of 30-day-old rats. The results suggest that the intensity of astrocyte proliferative response to injury cannot be regarded as simply being proportional to the developmental progress of the brain tissue. Rather, these results indicate that changes in glial proliferative responses to injury follow a developmental time course, with a peak around the end of the first postnatal week.

Aging↗

The first panic attack: a neurobiological theory.

We extend a neurodevelopmental model of specific phobias to the etiology of an initial panic attack and its elaboration into panic disorder. An important difference between the initial panic attack and specific phobia is the developmental timing of critical emotional experience: Those occurring early in development lead to panic; those occurring later in development lead to specific phobia. By this account, sensory and emotional experiences that occur early in development are stored in a set of modules, each with a unique developmental trajectory. Reinstatement, which occurs during hormonal stress, produces an aggregate of sensory and emotional memories and the first experience of an unexplained panic attack. Panic disorder, which evolves from unexplained panic attacks, involves retrieval of a disaggregate set of sensory and emotional memory fragments supplemented by an inferential fitting of an explanatory context to this incomplete aggregate.

Adult↗

Regulated activity of the IgH intron enhancer (E mu) in the T lymphocyte lineage.

The activity of the IgH (E mu) enhancer in the T lymphocyte lineage has been investigated using both transgenic mice and transfection studies. Thymocyte fractionation experiments indicate that a transgene consisting of the bacterial chloramphenicol acetyl transferase (CAT) gene, linked to E mu and the SV40 early promoter (E mu-CAT), is expressed only in thymocytes with a mature medullary phenotype and not in immature cells. Transfection of this same construct into two thymoma cell lines representing different stages of thymocyte development mimics the pattern of activity observed in vivo. Further transfection experiments suggest that this pattern of expression might be attributed to the differential activity of the E2E3 and octanucleotide motifs of E mu during development. In contrast, an Ig lambda transgene (linked to E mu and an Ig V lambda promoter) is expressed in the majority of thymocytes. We envisage that the different patterns of expression of the two transgenes reflect interactions between their respective promoters and the factors which are bound to E mu at different stages of thymocyte development. Although differing in their pattern of expression within the thymus, the two transgenes share the property of extinction in peripheral T lymphocytes. These results indicate that the expression of E mu-linked transgenes in the thymus cannot simply be explained by activation of the enhancer in a lymphoid progenitor cell prior to B/T lineage divergence. Rather, the enhancer (or components of it) must be independently activated (and inactivated) during T lymphocyte development. Furthermore, this activity is consistent with the developmental timing of Ig DH-JH rearrangements in these cells.

Animals↗

The relation between head size and auditory brain-stem response interpeak latency maturation.

In developmental populations, duration of auditory brain-stem response (ABR) I-III, III-V, and I-V vary substantially across individuals, particularly among preterm infants. Adult ABR interpeak latency has a strong correlation with brain-stem size and weaker correlation with head size. To determine if head size might contribute to this increased interpeak latency variability among infants, ABR data were normalized based on head circumference. Normalization by head circumference did not reduce interpeak variability. Further analyses revealed a negative correlation between interpeak latency and head circumference that varied as a function of age. Before 42 weeks conceptional age (CA), a significant relation exists between increased head circumference and decreased duration of the III-V and I-V intervals, but not the I-III interval. For infants older than 42 weeks CA, there was a significant relation between increased head circumference and decreased duration for the I-III intervals but not the III-V and I-V intervals. An age-dependent correlation between decreasing interpeak latency and increasing head circumference suggests that improved neural transmission through the auditory nerve and brain-stem pathway offset or even overcompensate for developmental lengthening of the sensory pathway. Also, developmental time constants obtained from nonlinear curve fit analyses were shorter for normalized than non-normalized data, particularly for the I-V interval. Therefore, correction of ABR data for the length of the sensory pathway may be important to estimate accurately maturation rate for developmental populations.

Acoustic Stimulation↗

Progressive divergence of definitive haematopoietic stem cells from the endothelial compartment does not depend on contact with the foetal liver.

The yolk sac and the para-aortic splanchnopleura/aorta-genital ridges-mesonephros (P-Sp/AGM) region are the main sites of haematopoietic activity in the mouse embryo at the pre-liver stage of development. By day 11.5 of gestation, the AGM region is capable of autonomous initiation and expansion of definitive haematopoietic stem cells (HSCs). By day 12.5, HSC activity in the AGM region is reduced whilst a second wave of HSCs begins to emerge in the yolk sac. We show here that HSCs emerging in both locations are marked by co-expression of the endothelial-specific marker VE-cadherin and the pan-leukocyte antigen CD45. Phenotypic characterisation using CD31, TIE2, FLK1, Ac-LDL receptors, and CD34 markers demonstrated significant similarities between this VE-cadherin+CD45+ ;double-positive' population and endothelial cells suggesting a common origin for these cells. The double-positive fraction also expressed the stem cell markers Kit, Sca1 and AA4.1. Long-term transplantation experiments demonstrated that the double-positive population, which constituted less than 0.05% of the day 11.5 AGM region and the day 12.5 yolk sac, is highly enriched for HSCs. In vitro assays showed that this population is also enriched for myeloid progenitors. During foetal liver colonization, circulating HSCs remained within the VE-cadherin+ cell fraction, although their phenotypic similarity with endothelial cells became less prominent. Upon liver colonisation the majority of HSCs downregulated VE-cadherin, expression of which was completely lost in the adult bone marrow. Partial loss of VE-cadherin expression in HSCs can be observed extra hepatically in the advanced AGM region by E12.5. Similarly, the CD34+KIT+ population in the placenta, recently identified as a reservoir of HSCs, partly lose VE-cadherin expression by E12.5. By culturing isolated E11.5 AGM region and E12.5 yolk sac we show that the developmental switch from a ;primary' VE-cadherin+CD45+ to a more ;advanced' VE-cadherin-CD45+ phenotype does not require contact of HSCs with the liver and is probably a function of developmental time.

Animals↗

Identifying infants and young children with developmental disorders in the medical home: an algorithm for developmental surveillance and screening.

Early identification of developmental disorders is critical to the well-being of children and their families. It is an integral function of the primary care medical home and an appropriate responsibility of all pediatric health care professionals. This statement provides an algorithm as a strategy to support health care professionals in developing a pattern and practice for addressing developmental concerns in children from birth through 3 years of age. The authors recommend that developmental surveillance be incorporated at every well-child preventive care visit. Any concerns raised during surveillance should be promptly addressed with standardized developmental screening tests. In addition, screening tests should be administered regularly at the 9-, 18-, and 30-month visits. (Because the 30-month visit is not yet a part of the preventive care system and is often not reimbursable by third-party payers at this time, developmental screening can be performed at 24 months of age. In addition, because the frequency of regular pediatric visits decreases after 24 months of age, a pediatrician who expects that his or her patients will have difficulty attending a 30-month visit should conduct screening during the 24-month visit.) The early identification of developmental problems should lead to further developmental and medical evaluation, diagnosis, and treatment, including early developmental intervention. Children diagnosed with developmental disorders should be identified as children with special health care needs, and chronic-condition management should be initiated. Identification of a developmental disorder and its underlying etiology may also drive a range of treatment planning, from medical treatment of the child to family planning for his or her parents.

Algorithms↗

Temperature-dependent development and population growth of Tetraneura nigriabdominalis (Homoptera: Pemphigidae) on three host plants.

The root aphid Tetraneura nigriabdominalis (Sasaki) (Homoptera: Pemphigidae) is a pest of many Gramineae species; however, little is known about its biology and relationships with host plants. The objectives of this study were to quantify the effects of temperature on development, longevity, fecundity, and population growth of T. nigriabdominalis and to assess the effects of host plant on development of T. nigriabdominalis. The effects of temperature on performance of this root aphid were determined at 10, 15, 20, 25, 30, and 35 +/- 1 degrees C on rice roots, Oryza sativa L. Nymphal stages from birth to adult decreased from 46.3 d at 10 degrees C to 8.5 d at 30 degrees C. Aphid survival and development were lowest at 35 degrees C, and no aphid produced progeny at this temperature. Average adult longevity decreased from 23.3 d at 15 degrees C to 8.2 d at temperatures up to 35 degrees C. Average number of nymphs produced per female was highest at 25 degrees C; averaging near 30 nymphs per female, but it dropped to near zero at both 10 and 35 degrees C. The highest intrinsic rate of increase (r(m)) was 0.241 at 30 degrees C. Net reproductive rate (R(0)) ranged from 29.8 at 25 degrees C to 0.2 at 10 degrees C. The generation time (GT) decreased with increasing temperatures from 60.3 d at 10 degrees C to 13.8 d at 30 degrees C. In addition, root aphids reared at 30 degrees C on three host plants [O. sativa, Zea mays L. and Sorghum bicolor (L.) Moench] revealed that the developmental time of the nymphal stages averaged 6.9 d when reared on O. sativa and 10.7 d when reared on Z. mays. Comparison of the nitrogen content of the three host plants indicated that the root nitrogen content was highest in O. sativa. The effect of nitrogen content on aphid performance, however, is still not clear. Other factors, such as plant secondary chemistry, may play a role in affecting aphid performance.

Animals↗

A morphologically conserved nonapoptotic program promotes linker cell death in Caenorhabditis elegans.

Apoptosis, cell death characterized by stereotypical morphological features, requires caspase proteases. Nonapoptotic, caspase-independent cell death pathways have been postulated; however, little is known about their molecular constituents or in vivo functions. Here, we show that death of the Caenorhabditis elegans linker cell during development is independent of the ced-3 caspase and all known cell death genes. The linker cell employs a cell-autonomous death program, and a previously undescribed engulfment program is required for its clearance. Dying linker cells display nonapoptotic features, including nuclear crenellation, absence of chromatin condensation, organelle swelling, and accumulation of cytoplasmic membrane-bound structures. Similar features are seen during developmental death of neurons in the vertebrate spinal cord and ciliary ganglia. Linker cell death is controlled by the microRNA let-7 and Zn-finger protein LIN-29, components of the C. elegans developmental timing pathway. We propose that the program executing linker cell death is conserved and used during vertebrate development.

Animals↗

Expression of Drosophila rhodopsins during photoreceptor cell differentiation: insights into R7 and R8 cell subtype commitment.

The R7 and R8 photoreceptor cells of the Drosophila retina are thought to mediate color discrimination and polarized light detection. This is based on the patterned expression of different visual pigments, rhodopsins, in different photoreceptor cells. In this report, we examined the developmental timing of retinal patterning. There is genetic evidence that over the majority of the eye, patterned expression of opsin genes is regulated by a signal from one subtype of R7 cells to adjacent R8 cells. We examined the onset of expression of the rhodopsin genes to determine the latest time point by which photoreceptor subtype commitment must have occurred. We found that the onset of rhodopsin expression in all photoreceptors of the compound eye occurs during a narrow window from 79% to 84% of pupal development (approximately 8 h), pupal stages P12-P14. Rhodopsin 1 has the earliest onset, followed by Rhodopsins 3, 4, and 5 at approximately the same time, and finally Rhodopsin 6. This sequence mimics the model for how R7 and R8 photoreceptor cells are specified, and defines the timing of photoreceptor cell fate decisions with respect to other events in eye development.

Animals↗

Aortic carboxypeptidase-like protein is expressed in collagen-rich tissues during mouse embryonic development.

Aortic carboxypeptidase-like protein (ACLP) was originally identified in vascular smooth muscle cells and contains discoidin and catalytically inactive metallocarboxypeptidase domains. ACLP is a secreted protein that associates with the extracellular matrix and is essential for abdominal wall development and contributes to dermal wound healing. Because of these developmental and adult phenotypes, we examined the expression of ACLP by immunohistochemistry throughout mouse embryonic development. ACLP was not detected in 7.5 days post-coitum (dpc) embryos, however at 9.5 dpc low levels of expression were detected in the somites and dorsal aorta. Expression was detected in both the yolk sac and embryonic vasculature at 10.5d pc. ACLP expression increased in both large and small blood vessels at 11.5 and 13.5 dpc and intense expression was detected within the vascular smooth muscle layer in 16.5 dpc embryos. At later developmental time points, discrete areas of ACLP expression were detected in the mesenchymal cells in the dermal layer, developing skeletal structures, connective tissue, and in the umbilical ring and vessels. The predominance of ACLP immunoreactivity localized with collagen-rich regions including tendons and basement membranes. Overall, the developmental expression pattern is consistent with a regulatory or structural role in the abdominal wall, vasculature, and dermis.

Animals↗

Acceleration of barrier ontogenesis in vitro through air exposure.

Immaturity of the epidermal barrier in the preterm infant may have serious clinical consequences. However, regardless of the degree of prematurity, the barrier rapidly matures such that by 2 wk all infants display a competent barrier. To determine whether the change from an aqueous (intrauterine) to a xeric environment might be the stimulus for this accelerated maturation, we examined the effects of air exposure on cutaneous barrier formation in vitro. Skin explants from d 17 fetal rats were incubated either submerged or at the air-medium interface. As previously reported, a competent barrier formed under submerged conditions after 3-4 d, precisely mirroring the time course of maturation in utero. In contrast, barrier maturation was accelerated in air-exposed explants, with functional, histologic, and structural markers of barrier formation observed after only 2 d of incubation. A water-impermeable membrane blocked the acceleration of barrier formation, resulting in a developmental time course comparable to that for submerged explants. In contrast a water vapor-permeable membrane did not block the acceleration. Glucocorticoids and thyroid hormone, which accelerate barrier formation in utero or in vitro under submerged conditions, did not further accelerate barrier formation in the air-exposed model. These data indicate that: 1) air exposure accelerates barrier ontogenesis, suggesting that water flux may be an important signal for the accelerated barrier formation that occurs in premature infants; and 2) factors which accelerate barrier formation in utero may not further accelerate barrier formation in neonates.

Air↗

Staging of middle and late embryonic development in the medicinal leech, Hirudo medicinalis.

We present a description of the last half of embryonic development in the European medicinal leech, Hirudo medicinalis, based entirely on externally visible morphological features, and establish reliably observable stages during that development. Embryogenesis, from the time fertilized eggs are deposited in an eggcase (called a cocoon) to the emergence of juveniles from the cocoon, takes approximately 4 weeks at room temperature. The stages described in this paper extend from the completion of segmentation to the appearance of the final bands of pigmentation. Developmental stages are expressed as percentages of total embryonic developmental time. This staging table was constructed for embryos kept at 20 degrees C. In addition, the development of animals kept at 17 degrees C or at 24 degrees C was compared with those held at 20 degrees C. Development proceeds more quickly at higher temperatures. Because development in embryos held at higher or lower temperatures was linearly related to the stages determined for embryos held at 20 degrees C, the rate of development at any intermediate temperature can be predicted from the staging table at 20 degrees C by simple multiplication.

Animals↗

Activation of nicotinic receptors uncouples a developmental timer from the molting timer in C. elegans.

C. elegans develops through four larval stages (L1 to L4) separated by molts. The identity of larval stages is mostly determined by stage-specific expression of heterochronic genes, which constitute an intrinsic genetic timer. However, extrinsic cues such as food availability or population density also modulate the developmental timing of C. elegans by mechanisms that remain largely unknown. To investigate a potential role of the nervous system in the temporal regulation of C. elegans development, we pharmacologically manipulated nicotinic neurotransmission, which represents a prominent signaling component in C. elegans nervous system. Exposure to the nicotinic agonist DMPP during post-embryonic development is lethal at the L2/L3 molt. Specifically, it delays cell divisions and differentiation during the L2 stage but does not affect the timing of the molt cycle, hence causing exposure of a defective L3 cuticle to the environment after the L2/L3 molt. Forcing development through a previously uncharacterized L2 diapause resynchronizes these events and suppresses DMPP-induced lethality. Nicotinic acetylcholine receptors (nAChRs) containing the UNC-63 subunit are required, probably in neurons, to trigger the action of DMPP. Using a forward genetic screen, we further demonstrated that the nuclear hormone receptor (NHR) DAF-12 is necessary to implement the developmental effects of DMPP. Therefore, a novel neuroendocrine pathway involving nAChRs and the NHR DAF-12 can control the speed of stage-specific developmental events in C. elegans. Activation of DMPP-sensitive nAChRs during the second larval stage uncouples a molting timer and a developmental timer, thus causing a heterochronic phenotype that is lethal at the subsequent molt.

Animals↗

Initial development of gamma-aminobutyric acid immunoreactivity in the human cerebral cortex.

The development of cortical cells immunoreactive for gamma-aminobutyric acid (GABA) was studied in human cerebral cortex in the first trimester of gestation (from 4 to 13 gestational weeks; g.w.). The first GABA-immunoreactive (IR) cells were observed at 6.5 g.w., i.e., before the appearance of the cortical plate, which gives rise to a majority of the adult cortical layers. GABA-IR cells were found initially in the telencephalic wall, where a lateromedial gradient in the density of GABA-positive cells was observed at this early developmental time point, but not at later stages. At 7 g.w., as the cortical plate emerged in the ventrolateral region of the cerebral vesicle, GABA-immunoreactive cells were found dorsal and ventral to the developing cortical plate. At this stage, immunoreactivity was also observed in the other transient developmental zones of the cortical anlage: in the subplate layer and in the intermediate, subventricular and ventricular zones. From 8 to 9 g.w. and continuing throughout the end of the studied period (13 g.w.), GABA-IR cells were distributed throughout the full width of the telencephalic wall, and, at 13 g.w., the newly formed subpial granular layer contained GABA-immunoreactive cells, as well. However, the predominant sites for GABA immunoreactivity remained the prospective layer I and the subplate. The population of GABA-positive cells described here was not immunoreactive for glial fibrillary acidic protein (GFAP) at any gestational age examined and, therefore, probably represents GABA-containing neurons. The observation that GABA-IR neurons appear in human developing cortex slightly before the cortical plate formation and beginning of synaptogenesis (6.5 g.w.) suggests that GABA plays an important role in the initial organization of the developing human cerebral cortex.

Cerebral Cortex↗

Temperature-related development of the parasitoid wasp Nasonia vitripennis as forensic indicator.

Development times of the forensically significant parasitic wasp Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae) from oviposition to pupation, and from oviposition to adult emergence, were studied in the laboratory at temperatures of 15-35 degrees C using host pupae of the blowfly Protophormia terraenovae (Robineau-Desvoidy) (Diptera: Calliphoridae). Total developmental time of N. vitripennis from oviposition to adult emergence (mean+/-SD) was 43.5+/-2.4, 22.5+/-1.1, 14.8+/-1.7 and 11.3+/-0.9 days when reared at 15, 20, 25 and 30 degrees C, respectively. At 35 degrees C, N. vitripennis did not develop successfully. The rate of total immature development (1/days) increased with temperature. From linear regression of development rates, it was determined that the minimum threshold (tL) for total immature development was 9.8 degrees C (approximately 10 degrees C). Above this threshold, the overall thermal constant (K) for N. vitripennis was found to be 224.3+/-1.7 degree-days.

Animals↗

Effect of regulated overexpression of the MADS domain factor AGL15 on flower senescence and fruit maturation.

We have examined the effect of regulated overexpression of AGL15, a member of the MADS domain family of regulatory factors, on reproductive tissues. Using molecular and physiological markers, we show that constitutive overexpression of AGL15 in Arabidopsis leads to delay and down-regulation of senescence programs in perianth organs and developing fruits and alters the process of seed desiccation. Through genetic crosses, we show that the rate of water loss in the maturing seeds is dictated by the genetic composition and physiological state of the maternal tissue, rather than the embryo. To define the developmental time and/or place when senescence programs are most affected by elevated AGL15 levels, we expressed AGL15 under the control of various promoters. Expression during senescence or in abscission zone cells did not produce delays in floral organ senescence or abscission. Using a glucocorticoid-inducible expression system, we show that an increase in AGL15 levels around the time of flower opening is necessary to delay senescence and increase floral organ longevity.

AGAMOUS Protein, Arabidopsis↗

Inhibition of glial maturation by bone morphogenetic protein 2 in a neural crest-derived cell line.

Bone morphogenetic proteins (BMPs) regulate developmental decisions in many neural and nonneural lineages. BMPs influence both CNS neuronal and glial development and promote neuronal differentiation in neural crest derivatives. We investigated the actions of BMP2 on glial differentiation in the peripheral nervous system using NCM1 cells, a neural crest-derived cell line with the properties of peripheral glial precursor cells. BMP2 prevented the acquisition of a mature Schwann cell-like morphology, blocking the expression of mature genes and maintaining expression of several early glial markers. We provide evidence that BMP2 activates the GFAP promoter and define signaling pathways underlying this regulation. Our results demonstrate a novel role for BMPs as inhibitors of glial differentiation in the peripheral nervous system and suggest that BMPs may regulate the developmental timing of glial maturation.

Animals↗

Genetic contribution to variation in larval development time, adult size, and longevity of starved adults of Anopheles gambiae.

The variation in mosquito life-history traits such as adult size has been studied with respect to environmental factors, but the genetic contribution to such variation has received almost no consideration. Using a full-sib design of F1s produced by wild caught Anopheles gambiae (M molecular form) females, we estimated broad-sense heritability of larval developmental time, adult size (based on dry weight and wing length), and longevity of starved adults. These traits were correlated (at the phenotypic level) with each other in females and males (|r(p)|>0.5, P<0.001). Longevity of starved adults increased with adult size, and both traits (adult longevity and size) decreased with longer larval development. Genetic correlations were lower (|r(g)|>0.45, P<0.05) but provided consistent evidence against a trade off between adult size and larval development time predicting that a mosquito can develop faster into a smaller adult or be a larger adult by a longer development. Estimates of heritability of the three traits were moderate to high (range: 0.05-0.48) and statistically significant (P<0.05), indicating substantial genetic contribution to the phenotypic variation in these traits. These results suggest that adaptive differences are likely to be found in these traits between A. gambiae populations.

Animals↗