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PubMed1998

Paralemmin, a prenyl-palmitoyl-anchored phosphoprotein abundant in neurons and implicated in plasma membrane dynamics and cell process formation.

We report the identification and initial characterization of paralemmin, a putative new morphoregulatory protein associated with the plasma membrane. Paralemmin is highly expressed in the brain but also less abundantly in many other tissues and cell types. cDNAs from chicken, human, and mouse predict acidic proteins of 42 kD that display a pattern of sequence cassettes with high inter-species conservation separated by poorly conserved linker sequences. Prenylation and palmitoylation of a COOH-terminal cluster of three cysteine residues confers hydrophobicity and membrane association to paralemmin. Paralemmin is also phosphorylated, and its mRNA is differentially spliced in a tissue-specific and developmentally regulated manner. Differential splicing, lipidation, and phosphorylation contribute to electrophoretic heterogeneity that results in an array of multiple bands on Western blots, most notably in brain. Paralemmin is associated with the cytoplasmic face of the plasma membranes of postsynaptic specializations, axonal and dendritic processes and perikarya, and also appears to be associated with an intracellular vesicle pool. It does not line the neuronal plasmalemma continuously but in clusters and patches. Its molecular and morphological properties are reminiscent of GAP-43, CAP-23, and MARCKS, proteins implicated in plasma membrane dynamics. Overexpression in several cell lines shows that paralemmin concentrates at sites of plasma membrane activity such as filopodia and microspikes, and induces cell expansion and process formation. The lipidation motif is essential for this morphogenic activity. We propose a function for paralemmin in the control of cell shape, e.g., through an involvement in membrane flow or in membrane-cytoskeleton interaction.

Amino Acid Sequence↗

PubMed2006

Identification of interventricular septum precursor cells in the mouse embryo.

Little is known about the formation of the interventricular septum (IVS), a central event during cardiogenesis. Here, we describe a novel population of myocardial progenitor cells in the primitive ventricle of the mouse embryo, which is characterized by expression of lysozyme M (lysM). Using LysM-Cre mice we show that lysozyme expressing cells give rise to the IVS and to a part of the left ventricular free wall, demonstrating that these heart regions are developmentally related. LysM+ precursors are not of hematopoietic origin and develop in the absence of transcription factors that regulate lysozyme expression in macrophages. LysM-deficient mice lack an overt cardiac phenotype, perhaps due to compensation by the related lysozyme P, which we also found to be expressed in the developing heart. Direct visualization of lysM expression, using LysM-EGFP knock-in mice, showed that ventricular septation is initiated at embryonic day 9 by the movement of myocardial trabeculae from the primitive ventricle towards the bulbo-ventricular groove and revealed the dynamics of IVS formation at later stages. Our studies predict that LysM-Cre mice will be useful to inactivate genes in the developing IVS.

Animals↗

PubMed2005

Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stages.

RNA interference (RNAi) is a naturally occurring posttranscriptional gene-silencing mechanism that has been adapted as a genetic tool for loss-of-function studies of a variety of organisms. It is more widely applicable than classical gene targeting and allows for the simultaneous inactivation of several homologous genes with a single transgene. Recently, RNAi has been used for conditional and conventional gene inactivation in mice. Unlike gene targeting, RNAi is a dynamic process, and its efficiency may vary both between cell types and throughout development. Here we demonstrate that RNAi can be used to target three separately encoded isoforms of the bcl-2 family gene bfl-1/A1 in a conditional manner in mice. The extent of gene inactivation varies between different cell types and is least efficient in mature lymphocytes. Our data suggest that RNAi is affected by factors beyond small interfering RNA-mRNA stoichiometry.

Animals↗

PubMed2005

Differential expression of tyrosinated tubulin in Spisula solidissima polar bodies.

The C-terminus of alpha-tubulin can be reversibly modified by a specific tyrosine ligase to yield an isoform known as Tyr-tubulin. Tyr-tubulin is typically found in more dynamic microtubule arrays such as the mitotic spindle, as opposed to stable structures like centrioles and flagella. In developing systems, it is expressed in relatively undifferentiated, proliferative cell types but is replaced by detyrosinated (Glu-) tubulin during differentiation. We found Tyr-tubulin highly enriched in a single polar body of Spisula solidissima embryos. Quantitation of DNA content by Hoechst staining indicates that polar body 1 (with twice the DNA content of polar body 2) is the Tyr-tubulin-positive cell. Other than the apoptosis marker caspase, this is, to our knowledge, the first distinguishing marker antigen for polar bodies, particularly for one polar body vs. another. This localization of Tyr-tubulin is unlikely to be a byproduct of the meiotic process itself, because it arises after ejection of both polar bodies is complete. Although polar bodies are typically thought of as a terminally differentiated vestige of meiosis, the localization of this more dynamic tubulin isoform suggests an active role in early development.

Animals↗

PubMed2002

Early environment shapes the development of gaze aversion by wild bonnet macaques (Macaca radiata).

Among many species of primates, staring is perceived as a sign of aggression and averting the gaze usually serves to reduce such conflict. The current study conducted in southern India documented developmental differences among wild bonnet macaques (Macaca radiata) in their latency to gaze avert after establishing eye contact with other individuals. Feeding stations were used to gather macaques within a small area to facilitate the video recording of group dynamics and eye contact between subordinate and dominant individuals. Individuals were grouped into three age classes: juveniles, subadult males, and adult males. Comparisons were also made between urban and forest dwelling troops. In the forest, juveniles established eye contact with older males for significantly longer periods of time than did adults. A linear trend was observed in which the latency to gaze avert after establishing eye contact decreased with age. This trend was not evident in the urban troops, for which the latency to gaze avert did not change significantly with age. Urban juveniles were also more likely to be chased when they established eye contact with adults compared with their forest counterparts. These differences could be the result of increased predatory risk in the forest setting - the necessity for heightened predator vigilance in forests may reduce the frequency with which juveniles are monitored and chased or attacked as a result of their eye contact. Conversely, the rarity of predators in the city may engender more intense aggressive behavior between monkeys, accelerating the rate of learning to signal appeasement to dominant males.

Age Factors↗

PubMed2003

Developmental responses to predation risk in morphologically defended mayflies.

Densities and species composition of predators could affect morphological defences, larval development and the timing of emergence of their prey. To address this issue we studied the morphology and life history of an ephemerellid mayfly, Ephemerella invaria, from two streams in a deciduous forested drainage basin in central New York. Both streams contained predatory fish, but densities and species composition of fish differed. A field survey provided evidence that Ephemerella inhabiting a stream with > or =10 fish species and high relative densities of fish emerged several weeks earlier and at smaller sizes than Ephemerella inhabiting a nearby tributary with approximately 2 fish species and low relative densities of fish. However, the two populations of mayflies showed no differences in defensive morphology or growth rates. In laboratory rearing experiments, we exposed Ephemerella larvae from these two locations to fish chemical cues or control water (no fish) over 2 months to test whether differences in life histories could be attributed to fish. Fish cues induced faster larval development, but also smaller size of mature Ephemerella individuals from both high and low predator locations. Although shorter development times in more dangerous environments could increase larval survival, smaller size of females results in a fecundity cost associated with this life history shift. Consistent with the field studies, laboratory rearing experiments revealed no effects of fish cues on Ephemerella's morphological defences. These data suggest that variation in the density or species composition of predators may favour the evolution of developmental plasticity to reduce mortality in the larval environment.

Adaptation, Physiological↗

PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed1995

Gnot1, a member of a new homeobox gene subfamily, is expressed in a dynamic, region-specific domain along the proximodistal axis of the developing limb.

Limb development endures as an excellent model for pattern formation in vertebrates. We have identified Gnot1 as a member of a new homeobox gene subfamily. Gnot1 is expressed in a dynamic temporospatial distribution in the developing limb, initially correlating with regions destined to form distal structures and then becoming progressively more restricted to specific regions determined to give rise to wrist and ankle. Micro-surgical alteration of the developmental program of the limb reveals that Gnot1 is expressed in a position- and fate-dependent manner, responding both to signals from the apical ridge and the polarizing zone. Furthermore, Gnot1 activation by polarizing signals occurs temporally downstream of Hoxd gene activation, but well before the first appearance of condensations that will give rise to the carpus of the wrist. The features of Gnot1 expression suggest a role for this gene in regulating pattern formation during limb development.

Age Factors↗

PubMed2003

Common tasks and problems in paediatric trauma radiology.

Scope of this article is to give practical hints for the most common, typical and important topics of trauma radiology in children to those radiologists who are not exclusively occupied with paediatric imaging. Due to the increased radiation sensitivity of children compared with adults balancing radiation protection and necessary image quality is of utmost importance. Outlines for this optimisation process are given. Especially in imaging of the extremities perhaps the greatest difficulties are posed by the dynamically changing face of the immature, growing, only partially ossified skeleton. Lack of experience must be compensated by meticulous comparison with the normal skeletal development as shown in standard textbooks, and by knowledge of the radiological image of the developmental variants. Besides general remarks about paediatric trauma radiology, some important topics are discussed into more detail. Especially the elbow joint poses a challenge for those less experienced with its radiological appearance in children. More than in adults, ultrasound should remain the primary imaging modality of choice especially in the assessment of abdominal trauma, and CT be tailored to radiological and clinical findings. Imaging and diagnosis of non-accidental injury (NAI) may be a less common task for the general radiologist, however, the severe social implications of physical child abuse mandate a basic knowledge about the radiological symptoms and the imaging management of this problem for all physicians occupied with paediatric radiology.

Child↗

PubMed2003

Somitogenesis: breaking new boundaries.

Segmentation is a fundamental process in vertebrate embryogenesis, and one of the earliest manifestations of segmental patterning is the generation of transient, serially repeated blocks of mesodermal cells known as somites. Disruption of the normal segmentation process in humans leads to vertebral abnormalities such as spondylocostal dysostosis. In this minireview, we discuss recent advances in the dynamic molecular and cellular mechanisms governing segmentation.

Animals↗

PubMed2002

Identification of novel Drosophila neural precursor genes using a differential embryonic head cDNA screen.

During Drosophila neuroblast lineage development, temporally ordered transitions in neuroblast gene expression have been shown to accompany the changing repertoire of functionally diverse cells generated by neuroblasts. To broaden our understanding of the biological significance of these ordered transitions in neuroblast gene expression and the events that regulate them, additional genes have been sought that participate in the timing and execution of these temporally controlled events. To identify dynamically expressed neural precursor genes, we have performed a differential cDNA hybridization screen on a stage specific embryonic head cDNA library, followed by whole-mount embryo in situ hybridizations. Described here are the embryonic expression profiles of 57 developmentally regulated neural precursor genes. Information about 2389 additional genes identified in this screen, including 1614 uncharacterized genes, is available on-line at 'BrainGenes: a search for Drosophila neural precursor genes' (http://sdb.bio.purdue.edu/fly/brain/ahome.htm).

Animals↗

PubMed1997

The chicken caudal genes establish an anterior-posterior gradient by partially overlapping temporal and spatial patterns of expression.

The caudal genes in vertebrates as in invertebrates assume a posterior position along the anterior-posterior axis and they appear to regulate the expression of the Hox genes. The third chicken caudal gene, Cdx-C, was cloned. Extensive comparisons of the sequence of this protein to the other known members of this homeobox family has lead to the suggestion that vertebrate genomes contain three members of the caudal homeobox family. A comparative study of the chicken Cdx-A and Cdx-C genes during gastrulation and neurulation revealed the differences between the genes. The caudal genes exhibit sequential activation in the newly formed neural plate and sequential extinction in axial midline structures during the primitive streak regression along the anterior-posterior axis. This pattern of expression suggests that the number and identity of caudal genes expressed along the anterior-posterior axis changes dynamically.

Amino Acid Sequence↗

PubMed2001

Regulating microtubule properties by modifying their organizing minus ends.

In the November 2001 issue of Developmental Cell, Vogel et al. describe that the budding yeast gamma-tubulin, Tub4p, is phosphorylated at a conserved tyrosine in G1 phase of the cell cycle. The results suggest that gamma-tubulin phosphorylation regulates the number and dynamics of microtubules.

Cell Cycle↗

PubMed1999

Russian neuropsychology after Luria.

It is now more than 20 years after Luria's death in 1977. His collaborators, disciples, and followers both in Russia and abroad continue to further develop his work. The development of Russian neuropsychology reflects the universal tendency to replace static neuropsychology, which relates individuals' behavior to fixed cerebral lesions, with dynamic neuropsychology, which analyzes the dynamics of brain-behavior interaction. Three types of Russian studies illustrate the latter approach: (1) neuropsychological follow-up of different nosological groups of patients in the process of medical or psychological treatment, (2) studies of cognitive evolution (developmental neuropsychology), and (3) studies of cognitive involution (neurogeriatrics). All studies focus on cortico-subcortical and interhemispheric relationships. Another change in modern Russian neuropsychology consists of combining the qualitative approach with the quantitative one, but the system of rating is based, following Luria's tradition, on the psychological evaluation of each task's structure and the qualitative analysis of the patients' performance and possibilities for its correction. Hence, Luria's creative and comprehensive approach stimulates the further development of neuropsychology in Russia.

History, 20th Century↗

PubMed2006

Proteomics identification of differentially expressed proteins associated with pollen germination and tube growth reveals characteristics of germinated Oryza sativa pollen.

Mature pollen from most plant species is metabolically quiescent; however, after pollination, it germinates quickly and gives rise to a pollen tube to transport sperms into the embryo sac. Because methods for collecting a large amount of in vitro germinated pollen grains for transcriptomics and proteomics studies from model plants of Arabidopsis and rice are not available, molecular information about the germination developmental process is lacking. Here we describe a method for obtaining a large quantity of in vitro germinating rice pollen for proteomics study. Two-dimensional electrophoresis of approximately 2300 protein spots revealed 186 that were differentially expressed in mature and germinated pollen. Most showed a changed level of expression, and only 66 appeared to be specific to developmental stages. Furthermore 160 differentially expressed protein spots were identified on mass spectrometry to match 120 diverse protein species. These proteins involve different cellular and metabolic processes with obvious functional skew toward wall metabolism, protein synthesis and degradation, cytoskeleton dynamics, and carbohydrate/energy metabolism. Wall metabolism-related proteins are prominently featured in the differentially expressed proteins and the pollen proteome as compared with rice sporophytic proteomes. Our study also revealed multiple isoforms and differential expression patterns between isoforms of a protein. These results provide novel insights into pollen function specialization.

Electrophoresis, Gel, Two-Dimensional↗

PubMed2001

Thalamo-cortical afferents control transient expression of the dopamine D(3) receptor in the rat somatosensory cortex.

The D(3) dopamine receptor (D(3)R) is selectively and transiently expressed in the barrel neurons of the somatosensory cortex (SI) between the first and second postnatal weeks. The D(3)R expression starts after the initial ingrowth of thalamocortical afferents (TCAs) into the barrel cortex and could be induced or controlled by them. We show that unilateral electrolytic lesion of the thalamic ventrobasal complex immediately after birth leads to a decrease in the D(3)R mRNA concentration in the lesioned SI 7 days after the lesion, whereas the D(3)R binding is little affected. Fourteen days after the neonatal thalamic lesion, the D(3)R binding and mRNA are drastically reduced and the barrel-like pattern of the D(3)R is absent. Elevation of the D(3) binding normally seen between the first and second postnatal weeks does not occur. Thalamic lesion on P6 differentially affects the D(3)R expression. One day after the lesion, the D(3) binding and mRNA are down-regulated, but the effect is transient. Five days after the lesion the concentration of D(3) mRNA in the lesioned hemisphere returns to the control level. The typical barrel-like pattern of D(3)R expression is evident in the lesioned SI, although TCAs are completely absent. Quantitative analysis demonstrated elevated cellular levels of the D(3) mRNA in barrel neurons 5 days after the lesion. These higher levels are needed, perhaps, to support the increased production of the D(3)R protein appropriate for this age. Age-related dynamics of the D(3)R binding is retained in the lesioned SI, although the concentration of D(3)R sites remains reduced. These data demonstrate that intact thalamic input is essential for the formation of mechanisms responsible for developmental regulation of the D(3)R expression in the SI.

Animals↗

PubMed2004

Capturing in vivo dynamics of the actin cytoskeleton stimulated by auxin or light.

We present here a transient expression system that allows the response of actin microfilaments to physiological stimuli (changes in auxin content, light) to be observed in single cells in vivo. Etiolated, intact rice seedlings are attached to glass slides, transfected biolistically with talin fused to yellow-fluorescent protein to visualize actin microfilaments, and either treated with auxin or irradiated. The talin marker labels distinct populations of actin that are differentially expressed depending on the physiological state of the coleoptile (active elongation versus ceased elongation). Whereas longitudinal transvacuolar bundles prevail in cells that have ceased to elongate, fine cortical strands are characteristic for elongating cells. The visualized actin structures remain dynamic and responsive to signals. Exogenous auxin triggers a loosening of the bundles and an extension of the cortical strands, whereas irradiation reorientates cortical strands into longitudinal arrays. These responses correspond in quality and timing to the signal responses inferred previously from fixed specimens and biochemical studies. In big advantage over those methods it is now possible to observe them directly at the single cell level. Thus, the rice coleoptile system can be used as a convenient model to study actin dynamics in vivo, in response to physiologically relevant stimuli.

Actin Cytoskeleton↗

PubMed1976

Child health clincs and inverse care laws: evidence from longitudinal study of 1878 pre-school children.

In a longitudinal study it was intended that 1878 children should receive periodic developmental examinations from the age of 6 weeks to 3 years. The children were divided into those with a high or low risk of developmental problems. Although clinic attendance rate of 85-89% were achieved in the catchment area 100% coverage was difficult because of population mobility and non-attendance at clinics. Children in families who moved away from the area were more difficult to trace and thus more likely to miss developmental examinations. This was a greater problem in the high-risk group. Altogether 683 home developmental examinations were carried out on 269 children who did not attend clinics. Thirty-five per cent of these children were in the high-risk group compared with 22% in the study population, and significantly more had developmental problems. Thus one possible way of reaching and helping such children is though home developmental examinations.

Child Development↗