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PubMed1985

Increasing team skills: an evaluation of program effectiveness.

The need for health professionals with caring values and good communication skills is well established. To develop these skills requires building self-esteem, as is supported by the work of Carl Rogers, Maslow, and Jourard, and the development of communication skills, as is supported by Carkhuff. A six-hour developmental program was evaluated using alternate forms of the highly validated Personal Skills Map. The differences in participants' scores showed increases in self-esteem, comfort, and management skills (p less than .00), while aggression (p = .05) and deference (p less than .00) decreased. A longitudinal follow-up of participants showed that 65% continued to use the assessment tool six months to one year later. The program appears to be well suited for service settings, continuing education, and academic settings, and meets the need of a high tech, high touch era of change.

Allied Health Personnel↗

PubMed2000

Localisation of 26S proteasomes with different subunit composition in insect muscles undergoing programmed cell death.

The 26S proteasome is a large multisubunit complex involved in degrading both cytoplasmic and nuclear proteins. We have investigated the subcellular distribution of four regulatory ATPase subunits (S6 (TBP7/MS73), S6' (TBP1), S7 (MSS1), and S10b (SUG2)) together with components of 20S proteasomes in the intersegmental muscles (ISM) of Manduca sexta during developmentally programmed cell death (PCD). Immunogold electron microscopy shows that S6 is located in the heterochromatic part of nuclei of ISM fibres. S6' is present in degraded material only outside intact fibres. S7 can be detected in nuclei, cytoplasm and also in degraded material. S10b, on the other hand, is initially found in nuclei and subsequently in degraded cytoplasmic locations during PCD. 20S proteasomes are present in all areas where ATPase subunits are detected, consistent with the presence of intact 26S proteasomes. These results are discussed in terms of heterogeneity of 26S proteasomes, 26S proteasome disassembly and the possible role of ATPases in non-proteasome complexes in the process of PCD. Cell Death and Differentiation (2000) 7, 1210 - 1217.

ATPases Associated with Diverse Cellular Activitie↗

PubMed1982

The KIDS chart. A simple, reliable infant development screening tool.

We describe a screening tool for infant development, the Kansas Infant Development Screen (KIDS). Validity data showed a very high correlation between developmental and chronologic age in 111 normal infants (r = .986). Among 96 infants and young children with delayed development, the results from use of the KIDS chart were compared with those obtained from a detailed evaluation using the Michigan Developmental Programming for Infants and Young Children, and the correlation was again high (r = .979). Interobserver reliability between use and observers in five different pediatric settings showed high correlations (r = .997). This seems to be a sensitive and reliable developmental screen. It is simple, requires only a few minutes to administer, and is helpful in following up children with both normal and delayed development. It portrays the infant's developmental level in a format that is readily understood by both professional and lay people.

Child Development↗

PubMed1994

Expression of desiccation-induced and lipoxygenase genes during the transition from the maturation to the germination phases in soybean somatic embryos.

Transitions between developmental programs during plant embryogenesis are usually characterized by differential gene expression. Soybean (Glycine max (L.) Merr.) somatic embryos from embryogenic suspension cultures germinate poorly on a germination medium even after being grown on medium containing abscisic acid until developmental changes are induced by desiccation. The objectives of this study were to investigate: (i) the relationship between water loss and germination of somatic embryos, (ii) changes in desiccation-induced polypeptides, and (iii) the expression of maturation- and germination-associated genes during the transition from maturation to germination of soybean somatic embryos. The results revealed that partial drying of somatic embryos at 76% relative humidity for 96 h resulted in more than 90% germination. Germination frequency was correlated with the percent fresh weight loss of the somatic embryos. Polypeptides induced by desiccation were classified into three groups based on the tissues in which they were expressed and the inducing agents to which they responded. Desiccation-induced polypeptides decreased or became undetectable upon inhibition. The expression of a maturation-associated gene, Mat1, was induced in both cotyledons and hypocotyl/radicle tissues of somatic embryos after 72 h desiccation. The transcript for this gene increased in concert with water loss from the embryos. During maturation of somatic embryos, the expression of embryonic lipoxygenase genes was turned on. Desiccation alone did not directly induce expression of germination-associated lipoxygenase genes SC514 and LOXB2 in somatic embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1992

Neuronal cell cultures: a tool for investigations in developmental neurobiology.

The aim of this review is to describe environmental requirements for survival of neuronal cells in culture, and secondly to survey the complex interplay between hormones, neurotrophic factors, transport- and extracellular matrix- proteins, which characterize the developmental program of differentiating neurons. An overall reconsideration of the literature in this vast field is above the limits of the present paper; since progress and refinement in the techniques of neuronal cell cultures have paralleled the advancement in Developmental Neurobiology, we will run instead through the main steps which form the conceptual framework of neuronal cell cultures.

Animals↗

PubMed2004

Sigma54 enhancer binding proteins and Myxococcus xanthus fruiting body development.

A search of the M1genome sequence, which includes 97% of the Myxococcus xanthus genes, identified 53 sequence homologs of sigma54-dependent enhancer binding proteins (EBPs). A DNA microarray was constructed from the M1genome that includes those homologs and 318 other M. xanthus genes for comparison. To screen the developmental program with this array, an RNA extract from growing cells was compared with one prepared from developing cells at 12 h. Previous reporter studies had shown that M. xanthus has initiated development and has begun to express many developmentally regulated genes by 12 h. The comparison revealed substantial increases in the expression levels of 11 transcription factors that may respond to environmental stimuli. Six of the 53 EBP homologs were expressed at significantly higher levels at 12 h of development than during growth. Three were previously unknown genes, and they were inactivated to look for effects on fruiting body development. One knockout mutant produced fruiting bodies of abnormal shape that depended on the composition of the medium.

Amino Acid Sequence↗

PubMed1998

Common role for each of the cGATA-4/5/6 genes in the regulation of cardiac morphogenesis.

The GATA-4/5/6 genes encode transcription factors implicated previously in the regulation of cardiac-specific differentiation programs. However, recent analyses of mouse GATA-4 null mutations found evidence for function in endoderm development (in vitro) and embryonic morphogenesis (in vivo). Whether each of the three cardiac-associated GATA factors function within distinct or common developmental programs was previously untested; past studies defined specific and distinct roles for each of the GATA-1/2/3 genes in embryonic hematopoiesis. In this study, we compare the transcript patterns of cGATA-4/5/6 during chick embryogenesis. Each of the three GATA factors is expressed in a similar pattern within gastrulating cells of the primitive streak, prior to determination of the cardiomyocyte progenitors, and later within the lateral plate mesoderm and associated endoderm layer. The patterns overlap but extend beyond the presumptive cardiomyocyte population expressing cNkx-2.5. Later in development, cGATA-4/5/6 are all transcribed throughout the differentiating heart, in similar but not identical patterns, within the endocardium, myocardium, and great vessels. In order to test the function of GATA factors during chick cardiogenesis, embryos were cultured in vitro in the presence of antisense oligomers designed to deplete specifically transcripts encoding cGATA-4/5/6, beginning around stage 7. When oligomers are used to target transcripts for all three genes, a high percentage of the embryos develop abnormal hearts related to the failure to form a normal primitive heart tube. In the most severe phenotype, cardiac bifida results in two bilateral beating hearts. In some embryos, the paired heart primordia undergo partial fusion but fail to form a single looping heart tube. In all cases, cellular differentiation is not obviously affected, as the abnormal hearts form beating tissue. Depletion of transcripts encoding any single GATA factor, or any combination of two GATA factors, does not affect development. The partial depletion of all three genes in chick results in a remarkably similar phenotype compared to the null GATA-4 mutation in mouse. Therefore, in the chick, each of the GATA-4/5/6 genes functions in a common pathway, at the time of cardiac crescent formation, for regulating early embryonic cardiac morphogenesis, apparently associated with embryonic folding or the migration of primordia to form a primitive tube.

Animals↗

PubMed2004

Chromatin landscape dynamics of the Il4-Il13 locus during T helper 1 and 2 development.

Il4 and Il13 encode the canonical T helper 2 (TH2) cytokines responsible both for promoting immune responses against extracellular pathogens and, when misregulated, causing allergic and autoimmune disease. The expression potential of these genes undergoes developmentally programmed repression and enhancement during commitment of naïve CD4+ T cells to the mature T helper 1 (TH1) and TH2 fates, respectively. Thus, like the globin locus, the TH2 cytokine locus provides a highly tractable system to study a developmental fate choice leading to alternative transcriptional states of either silence or permissivity. We used quantitative chromatin immunoprecipitation and RT-PCR to correlate changes in the transcriptional states of Il4 and Il13 with markers of permissive chromatin across the Il4-Il13 locus in naïve CD4+ T cells undergoing TH1 and TH2 differentiation. We provide evidence that DNaseI hypersensitive site V in the Il4 3' enhancer is the likely target for signals maintaining Il4 and Il13 transcriptional permissivity in naïve cells. We also demonstrate rapid acquisition of differences in H3 acetylation between TH1- and TH2-primed cells, indicating a developmentally early role for cytokine signaling in the process of TH cell fate determination. Finally, we show that transcriptional repression correlates with the disappearance of permissive H3 modifications from everywhere in the Il4-Il13 locus except hypersensitive site IV, suggesting a critical role for this element in the maintenance of transcriptional repression. Our findings are consistent with a progressive regulatory element activation/deactivation model of TH1/TH2 development.

Acetylation↗

PubMed2006

Deciphering the underlying mechanism of specification and differentiation: the sea urchin gene regulatory network.

The regulatory genome functions as a vast information processor through development. It processes the initial conditions that are set by asymmetric distributions of cellular components in the egg and translates them into the onset of spatially localized specification states. It regulates the timely differential activation of signaling molecules and transcription factors that divide the emerging domains into subdomains. It also governs the activation of groups of differentiation genes, the genes that encode, at the protein level, the functional and the structural properties of a cell type. The sea urchin endomesoderm gene regulatory network provides a window into the different levels of the regulatory apparatus. It demonstrates how the static physical genomic components define functional connections between the various regulatory genes that act together to conduct the dynamical developmental program.

Animals↗

PubMed2006

MicroRNA responses to cellular stress.

Recent work has begun to explore the instrumental role that small noncoding RNA species, particularly microRNAs (miRNA), have both in classifying human tumors and in directing embryonic development. These studies suggest that developmental programs in essentially all organisms studied are set, in part, by varied expressions of miRNAs and that neoplasia is characterized by altered expression of miRNAs. Reasoning that these observations are linked, we examined whether cellular exposures that induce both developmental anomalies and cancer alter miRNAs. Using microarrays of 385 known human miRNAs, we studied human lymphoblastoid cells grown under various conditions or treatments. Folate deficiency induced a pronounced global increase in miRNA expression. We observed no significant alteration in miRNA expression in cells treated with gamma-irradiation, whereas exposure to sodium arsenite led to global increases in miRNA expression. The miRNA hsa-miR-222 was identified from these arrays as significantly overexpressed under folate-deficient conditions, and this finding was confirmed in vivo in human peripheral blood from individuals with low folate intake. Alterations to cellular miRNA expression profiles represent a novel mode of action of folate deprivation and arsenic exposure, and specific alterations in miRNA expression may be a powerful biomarker for these and other toxins with serious effects on human health.

Arsenites↗

PubMed1990

The developmental fate of fission yeast cells is determined by the pattern of inheritance of parental and grandparental DNA strands.

A key feature for development consists of producing sister cells that differ in their potential for cellular differentiation. Following two cell divisions, a haploid Schizosaccharomyces pombe cell produces one cell in four 'granddaughters' with a changed mating cell type, implying nonequivalence of sister cells in each of two consecutive cell divisions. The observed pattern of switching is analogous to the mammalian 'stem cell' lineage by which a cell produces one daughter like itself while the other daughter is advanced in its developmental program. It is tested here whether sisters differ because of unequal distribution of cytoplasmic and/or nuclear components to them or due to inheriting a specific parental DNA chain at the mating type locus. Only the DNA strand-segregation model predicts that those cells engineered to contain an inverted tandem duplication of the mating type locus should produce equivalent sisters. Consequently, two 'cousins' in four related granddaughter cells should switch. The results verified the prediction, thus establishing that all cells otherwise fully possess the potential to switch. Therefore, the program of cell type change in S.pombe cell lineages is determined by the pattern of DNA strand inheritance at the mating type locus. A specific DNA sequence present at the mating type locus is postulated to be the cause of developmental asymmetry between sister cells. A general model for cellular differentiation is proposed in which the act of DNA replication itself is hypothesized to produce developmentally nonequivalent sister genomes.

DNA, Fungal↗

PubMed1994

Regulation of gene expression programs during Arabidopsis seed development: roles of the ABI3 locus and of endogenous abscisic acid.

The accumulation kinetics of 18 mRNAs were characterized during Arabidopsis silique development. These marker mRNAs could be grouped in distinct classes according to their coordinate temporal expression in the wild type and provided a basis for further characterization of the corresponding regulatory pathways. The abscisic acid (ABA)-insensitive abi3-4 mutation modified the expression pattern of several but not all members of each of these wild-type temporal mRNA classes. This indicates that the ABI3 protein directly participates in the regulation of several developmental programs and that multiple regulatory pathways can lead to the simultaneous expression of distinct mRNA markers. The ABI3 gene is specifically expressed in seed, but ectopic expression of ABI3 conferred the ability to accumulate several seed-specific mRNA markers in response to ABA in transgenic plantlets. This suggested that expression of these marker mRNAs might be controlled by an ABI3-dependent and ABA-dependent pathway(s) in seed. However, characterization of the ABA-biosynthetic aba mutant revealed that the accumulation of these mRNAs is not correlated to the ABA content of seed. A possible means of regulating gene expression by developmental variations in ABA sensitivity is apparently not attributable to variations in ABI3 cellular abundance. The total content of ABI3 protein per seed markedly increased at certain developmental stages, but this augmentation appears to result primarily from the simultaneous multiplication of embryonic cells. Our current findings are discussed in relation to their general implications for the mechanisms controlling gene expression programs in seed.

Abscisic Acid↗

PubMed1997

Regulation of the Caulobacter flagellar gene hierarchy; not just for motility.

The Caulobacter crescentus flagellum serves not only as a motility apparatus, but also as a key landmark in the differentiation of this asymmetrically dividing bacterium. A distinctive aspect of flagellum biosynthesis is the periodic expression of the flagellar genes during the cell cycle in a sequence corresponding to the order of gene product assembly into the growing flagellum. This program of gene expression is achieved in part by the organization of flagellar genes into a four-tiered regulatory hierarchy that controls their expression at both the transcriptional and post-transcriptional levels. Because of the close interconnection of the developmental program to the asymmetric cell-division cycle in C. crescentus, studies of flagellar gene regulation and motility have also begun to reveal basic mechanisms responsible for control of the cell cycle itself. Here, we review recent work on regulation of the flagellar gene hierarchy in C. crescentus and consider regulatory mechanisms that are distinct from those described in Escherichia coli and Salmonella typhimurium.

Caulobacter crescentus↗

PubMed2000

Ama1p is a meiosis-specific regulator of the anaphase promoting complex/cyclosome in yeast.

Meiosis is the developmental program by which diploid organisms produce haploid gametes capable of sexual reproduction. Here we describe the yeast gene AMA1, a new member of the Cdc20 protein family that regulates the multisubunit ubiquitin ligase termed the anaphase promoting complex/cyclosome (APC/C). AMA1 is developmentally regulated in that its transcription and splicing occur only in meiotic cells. The meiosis-specific processing of AMA1 mRNA depends on the previously described MER1 splicing factor. Several results indicate that Ama1p is required for APC/C function during meiosis. First, coimmunoprecipitation assays indicate that Ama1p associates with the APC/C in vivo. Second, Ama1p is required for the degradation of the B-type cyclin Clb1p, an APC/C substrate in both meiotic and mitotic cells. Third, ectopic overexpression of AMA1 is able to stimulate ubiquitination of Clb1p in vitro and degradation of Clb1p in vivo. Mutants lacking AMA1 revealed that it is required for the first meiotic division but not the mitotic-like meiosis II. In addition, ama1 mutants are defective for both spore wall assembly and the expression of late meiotic genes. In conclusion, this study indicates that Ama1p directs a meiotic APC/C that functions solely outside mitotic cell division. The requirement of Ama1p only for meiosis I and spore morphogenesis suggests a function for APC/C(Ama1) specifically adapted to germ cell development.

Amino Acid Sequence↗

PubMed1977

Linkage of genetic determinants for mouse beta-galactosidase electrophoresis and activity.

An electrophoretic polymorphism for beta-galactosidase has been identified among common inbred strains of mice. It is inherited as a single Mendelian factor with two alleles showing codominant expression. This structural gene, Bge, is closely linked (0/163 recombinants) with the Bgs site on chromosome 9 which regulates systemic levels of beta-galactosidase. The distribution of electrophoretic and activity phenotypes among inbred strains is not concordant, indicating that they result from separate mutations. Three aspects of beta-galactosidase realization, its structure, systemic regulation and developmental program, are now known to be organized in close proximity on chromosome 9. Considered in conjuction with evidence from other mammalian systems, this suggests that the mammalian genome, like Drosophila, is organized into large functional units in which relevant regulatory and developmental information is closely associated with individual structural genes.

Alleles↗

PubMed2006

Molecular programming of stem cells into mesodiencephalic dopaminergic neurons.

In a screen for homeobox transcription factors expressed in the embryonic ventral midbrain, Andersson et al. recently identified Lmx1a and Msx1. Using in ovo electroporation in chick embryos, they showed that these factors are crucial for initiating the differentiation of neuroepithelial progenitor neurons into mesodiencephalic dopaminergic (mdDA) neurons. Lmx1a also initiated a developmental program that drove an mdDA phenotype in mouse embryonic stem cells. This indicates that these factors can be exploited in cell-replacement strategies for treatment of Parkinson's disease.

Animals↗

PubMed1999

Homeotic genes and the arthropod head: expression patterns of the labial, proboscipedia, and Deformed genes in crustaceans and insects.

cDNA fragments of the homologues of the Drosophila head homeotic genes labial (lab), proboscipedia (pb), and Deformed (Dfd) have been isolated from the crustacean Porcellio scaber. Because the accumulation domains of the head homeotic complex (Hox) genes had not been previously reported for crustaceans, we studied the expression patterns of these genes in P. scaber embryos by using in situ hybridization. The P. scaber lab homologue is expressed in the developing second antennal segment and its appendages. This expression domain in crustaceans and in the homologous intercalary segment of insects suggests that the lab gene specified this metamere in the last common ancestor of these two groups. The expression domain of the P. scaber pb gene is in the posterior part of the second antennal segment. This domain, in contrast to that in insects, is colinear with the domains of other head genes in P. scaber, and it differs from the insect pb gene expression domain in the posterior mouthparts, suggesting that the insect and crustacean patterns evolved independently from a broader ancestral domain similar to that found in modern chelicerates. P. scaber Dfd is expressed in the mandibular segment and paragnaths (a pair of ventral mouthpart structures associated with the stomodeum) and differs from insects, where expression is in the mandibular and maxillary segments. Thus, like pb, Dfd shows a divergent Hox gene deployment. We conclude that homologous structures of the mandibulate head display striking differences in their underlying developmental programs related to Hox gene expression.

Amino Acid Sequence↗

PubMed2006

Ubc9 regulates mitosis and cell survival during zebrafish development.

Many proteins are modified by conjugation with Sumo, a gene-encoded, ubiquitin-related peptide, which is transferred to its target proteins via an enzymatic cascade. A central component of this cascade is the E2-conjugating enzyme Ubc9, which is highly conserved across species. Loss-of-function studies in yeast, nematode, fruit fly, and mouse blastocystes point to multiple roles of Ubc9 during cell cycle regulation, maintenance of nuclear architecture, chromosome segregation, and viability. Here we show that in zebrafish embryos, reduction of Ubc9 activity by expression of a dominant negative version causes widespread apoptosis, similar to the effect described in Ubc9-deficient mice. However, antisense-based knock down of zygotic ubc9 leads to much more specific defects in late proliferating tissues, such as cranial cartilage and eyes. Affected cartilaginous elements are of relatively normal size and shape, but consist of fewer and larger cells. Stainings with mitotic markers and 5-Bromo-2'-deoxyuridine incorporation studies indicate that fewer chondrocyte precursors are in mitosis, whereas the proportion of cells in S-phase is unaltered. Consistently, FACS analyses reveal an increase in the number of cells with a DNA content of 4n or even 8n. Our data indicate an in vivo requirement of Ubc9 for G2/M transition and/or progression through mitosis during vertebrate organogenesis. Failed mitosis in the absence of Ubc9 is not necessarily coupled with cell death. Rather, cells can continue to replicate their DNA, grow to a larger size, and finish their normal developmental program.

Animals↗