Mammalian sex determination: a molecular drama.
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Animals↗
Biomedical subjects
A Swain
Publications and source records attributed to A Swain.
Developmental genetics. Too much sex is bad for males.
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Animals↗
Dax1 antagonizes Sry action in mammalian sex determination.
DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females. XY mice carrying extra copies of mouse Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Complete sex reversal occurs, however, when the transgene is tested against weak alleles of the sex-determining Y-chromosome gene Sry. These results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.
Animals↗
A molecular approach to sex determination in mammals.
Mammalian sex determination occurs in the gonad of the developing embryo. This process is dependent on the Y-chromosome-encoded Sry gene that acts in the somatic cells of the genital ridge. The transient nature of Sry gene expression suggests that it acts as a switch from one cell fate to another. One of the roles of Sry is to initiate the differentiation of Sertoli cells, which are the first cell type of the testis to be formed. Two genes are thought to be important in Sertoli cell differentiation and function, Sox9, an Sry-related gene, and SF-1, a nuclear hormone receptor. Sox9 is expressed in Sertoli cells throughout development of the mouse embryo, and inactivating mutations in this gene in humans give rise to XY females. SF-1 is also expressed in Sertoli cells and is thought to activate the AMH gene--an early marker of these cells. DAX-1, an X-linked member of the nuclear hormone superfamily, is a candidate for a human condition in which duplication of regions of the X chromosome results in XY females. Expression of this gene during mouse development is associated with ovary development and is down-regulated in the differentiating testis. Mutations in DAX-1 in humans have shown that this gene is not necessary for testis development. The properties of the DAX-1 gene suggest that it is important in ovary determination and might therefore be antagonistic to the action of the Sry gene.
Animals↗
Steroidogenic factor 1 plays multiple roles in endocrine development and function.
The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also contains members for which activating ligands have not been identified-the orphan nuclear receptors. One of these orphan nuclear receptors, steroidogenic factor 1 (SF-1), has emerged as an essential regulator of steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays important roles in reproduction at all three levels of the hypothalamic-pituitary-gonadal axis. First identified as a tissue-specific regulator of the transcription of the cytochrome P450 steroid hydroxylases, considerably broader roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal glands and gonads, male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels. Despite these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts its multiple effects remain to be determined. This review highlights experiments that have established SF-1 as a pivotal determinant of endocrine differentiation and function and identifies areas in which additional studies are needed to expand our understanding of SF-1 action.
Animals↗
Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.
Duplications of a chromosome Xp21 locus DSS (Dosage Sensitive Sex reversal) are associated with male to female sex reversal. An unusual member of the nuclear hormone receptor superfamily, DAX1, maps to the DSS critical region and is responsible for X-linked adrenal hypoplasia congenita. Here we describe the isolation of the mouse Dax1 gene and its pattern of expression during development. Expression was detected in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus. Moreover, Dax1 expression is down-regulated coincident with overt differentiation in the testis, but persists in the developing ovary. Comparison of the predicted protein products of the human and mouse genes show that specific domains are evolving rapidly. Our results suggest a basis for adrenal insufficiency and hypogonadotropic hypogonadism in males affected by adrenal hypoplasia congenita and are consistent with a role for DAX1 in gonadal sex determination.
Adrenal Glands↗
Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds.
Heterozygous mutations in SOX9 lead to a human dwarfism syndrome, Campomelic dysplasia. Consistent with a role in sex determination, we find that Sox9 expression closely follows differentiation of Sertoli cells in the mouse testis, in experimental sex reversal when fetal ovaries are grafted to adult kidneys and in the chick where there is no evidence for a Sry gene. Our results imply that Sox9 plays an essential role in sex determination, possibly immediately downstream of Sry in mammals, and that it functions as a critical Sertoli cell differentiation factor, perhaps in all vertebrates.
Amino Acid Sequence↗
Social loafing and identifiability: the mediating role of achievement goal orientations.
The purpose of this investigation was to determine if differences in the tendency to exhibit social loafing is a function of achievement-goal orientation and identifiability. Ninety-six males drawn from 10th-grade physical education classes responded to the Task and Ego Orientation in Sport Questionnaire (Duda, 1992) prior to completing a 30-meter sprint task under three separate conditions: as an individual, in a team with individual performance identified, and in a team with individual performance not identified. Following a median split of the task and ego values reported, subjects were divided into high and low groups for both orientations. Sprint times were compared by means of a 2 x 2 x 3 ANOVA (task x ego x sprint condition) with repeated measures on the third factor. Findings revealed that individuals with a combined low task/high ego orientation were significantly slower in the nonidentifiable team condition than in the other two conditions, whereas high-task/low-ego-oriented individuals demonstrated consistent performance across all three conditions. While confirming that identifiability of performance is an important situational variable, the findings suggest that the dispositional factor of achievement orientation may interact to provide a more detailed explanation of the social loafing phenomenon.
Achievement↗
Reproducibility of blood pressure and heart rate reactivity: a meta-analysis.
Reproducibilities of blood pressure and heart rate (HR) reactivity reported in studies assessing responses to the same laboratory stressors across occasions were reviewed with meta-analytic techniques. Changes in HR had the greatest reproducibility (r = .555), followed by systolic blood pressure (SBP) (.407) and diastolic blood pressure (DBP) (.348). Both SBP and HR response reproducibility was higher at shorter test-retest intervals, whereas DBP values varied unsystematically with length of test-retest interval. Older samples exhibited higher SBP and DBP reproducibility to stressors. SBP and DBP reproducibilities were better for tasks that did not make speech demands. The reliability of reactivity assessment was higher when based on three or more measurements. On the basis of available evidence, the drop in stress reproducibility, as test-retest interval increases, places limits on the viability of BP reactivity as a strong marker or risk factor for coronary heart disease.
Aging↗
Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development.
Mutations of the orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, cause complex endocrine phenotypes that include impaired adrenal development and hypogonadotrophic hypogonadism. These similar phenotypes suggest that SF-1 and DAX-1 act in the same pathway(s) of endocrine development. To explore this model, we now compare directly their sites of expression. In mouse embryos, SF-1 expression in the urogenital ridge and brain either preceded or coincided with Dax-1 expression, with coordinate expression thereafter in the adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary. The striking colocalization of SF-1 and Dax-1 supports the model that they are intimately linked in a common pathway of endocrine development. The slightly earlier onset of SF-1 expression and its ability to bind specifically to a conserved sequence in the Dax-1 5'-flanking region suggested that SF-1 may activate Dax-1 expression. However, promoter activity of Dax-1 5'-flanking sequences did not require this potential SF-1-responsive element, and Dax-1 expression was unimpaired in knockout mice lacking SF-1, establishing that SF-1 is not required for Dax-1 gene expression in these settings. Although the precise mechanisms remain to be established and may be multifactorial, our results strongly suggest that these two orphan nuclear receptors interact in a common pathway of endocrine development.
Animals↗
Japanese encephalitis in Orissa.
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Encephalitis, Japanese↗
Effects of goal-setting interventions on selected basketball skills: a single-subject design.
The purpose of this investigation was to examine the effects of a goal-setting intervention program on selected components of basketball performance over the course of a competitive season. A multiple-baseline, single-subject design was used with baseline observations on various performance components (e.g., turnovers, rebounds), collected for four elite college basketball players during their first eight games of the season. At the midseason break, these players selected one aspect of their play that they felt would benefit from improvement. A goal-setting program was designed based on the goal attainment scaling procedure recommended by Smith (1988), whereby subjects generated numerical targets for their chosen components. Performance components were then assessed for the next eight games as they had been in the preintervention phase. Following the intervention, 3 of the 4 subjects showed consistent improvements in their targeted areas of performance. Also, there were no outcome changes in the performance components that weren't targeted by the subjects. The findings suggest that future studies may benefit from achieving greater ecological validity and utilizing alternative designs to the traditional nomothetic approaches which may tend to mask positive intervention effects on certain individuals.
Adult↗
Circular transcripts of the testis-determining gene Sry in adult mouse testis.
Sry is expressed at higher levels in the adult testis, where no function has been determined, than in the genital ridge, its critical site of action. cDNA and 5' RACE clones isolated from testis or from Sry-transfected cell lines have an unusual structure, with 3' sequences located in a 5' position. RNAase protection assays and reverse transcription polymerase chain reactions confirmed that these unusual RNA molecules represent the most abundant transcript in testis. Furthermore, oligonucleotide hybridization and RNAase H digestion proved that these Sry RNA molecules are circular. Similar transcripts were detected in the testes of mice with Mus musculus musculus, Mus musculus domesticus, and Mus spretus Sry genes. The circular RNA is found in the cytoplasm but is not substantially bound to polysomes. We suggest that the circles arise from normal splicing processes as a consequence of the unusual genomic structure surrounding the Sry locus in the mouse.
Animals↗
Intensity and direction dimensions of competitive state anxiety and relationships with performance.
This study examined relationships between intensity and direction dimensions of competitive state anxiety, and also relationships with beam performance in a sample of female gymnasts. The 48 gymnasts, whose ages ranged from 14 to 16 years, competed in a beam competition and were divided, via the median split technique, into poor performance and good performance groups. All the subjects completed a modified version of the Competitive State Anxiety Inventory-2 (CSAI-2) 10 min prior to performance. This inventory included the original intensity scale plus a direction scale in which subjects rated the degree to which the experienced intensity of each symptom was either facilitative of debilitative to subsequent beam performance. Analyses of variance showed no significant group differences on any of the CSAI-2 sub-component intensity scores, or on somatic anxiety and self-confidence direction scores. However, the good performance group reported their cognitive anxiety intensity as being more facilitating and less debilitating to performance than the poor performance group. Stepwise multiple-regression analyses showed that the only significant predictor of beam performance was self-confidence intensity. These findings support the proposal that sports performers' directional perceptions of their anxiety symptoms may provide further understanding of the competitive state anxiety response, and also emphasize the importance of self-confidence in predicting performance.
Adolescent↗
Intensity and frequency dimensions of competitive state anxiety.
This study reports a preliminary investigation of intensity and frequency of symptoms of competitive state anxiety. Forty-nine track and field athletes (27 males, 22 females) responded to a modified version of the Competitive State Anxiety Inventory-2 (CSAI-2) on four occasions during the period leading up to an important competition: 2 days, 1 day, 2 h and within 30 min of competing. The questionnaire included the existing CSAI-2 (intensity) scale as well as a frequency scale for each of the 27 items of the CSAI-2. The intensity and frequency dimensions of each of the CSAI-2-sub-scales were then compared between the four conditions by means of two-way analyses of variance (gender x time-to-competition). In the case of cognitive anxiety, time-to-event effects were observed for intensity and frequency for both males and females. The intensity of the response was significantly greater at the final stage of testing than it was 2 days before competition, while the frequency of the response increased progressively throughout the experimental period. This dissociative patterning for the cognitive anxiety dimensions is discussed in the light of Multidimensional Anxiety Theory predictions. For somatic anxiety, the time-to-event effects that emerged for intensity and frequency revealed that both values increased progressively as the time to compete neared, for both male and females. The results for self-confidence revealed no effects for intensity or frequency for either gender. The findings from structured follow-up interviews served to corroborate these quantitative findings by providing information that supported the conclusions drawn from the questionnaire data. In particular, the athletes reported that they experienced considerable increases in the frequency of intrusive anxiety cognitions. While these findings clearly need to be substantiated, they do provide evidence of the existence of an additional dimension of anxiety that may assist our understanding of this complex concept. The measurement of competitive state anxiety may benefit from this more detailed approach as opposed to the rather limited intensity-alone perspective.
Adult↗
Influence of sequences in the long terminal repeat and flanking cell DNA on polyadenylation of retroviral transcripts.
Readthrough transcripts are formed during retrovirus infection by polyadenylation of viral RNA in cellular sequences adjacent to the provirus. We have studied such transcripts in avian leukosis virus-infected cell clones containing a single provirus, either the wild type or one with an inactivating mutation in the poly(A) addition signal. All individual wild-type proviruses produced readthrough transcripts, implying that this property is not restricted to a few integration sites. The range of sizes of viral RNA in the mutant lacking a correct signal for poly(A) addition reflected both the occurrence of functional polyadenylation sites within flanking cell DNA and increased usage of cryptic sites within viral sequences.
Animals↗
Mechanism of transduction by retroviruses.
Retroviruses can capture cellular sequences and express them as oncogenes. Capture has been proposed to be a consequence of the inefficiency of polyadenylation of the viral genome that allows the packaging of cellular sequences flanking the integrated provirus in virions; after transfer into virions, these sequences could be incorporated into the viral genome by illegitimate recombination during reverse transcription. As a test for this hypothesis, a tissue culture system was developed that mimics the transduction process and allows the analysis and quantitation of capture events in a single step. In this model, transduction of sequences adjacent to a provirus depends on the formation of readthrough transcripts and their transmission in virions and leads to various recombinant structures whose formation is independent of sequence similarity at the crossover site. Thus, all events in the transduction process can be attributed to the action of reverse transcriptase on readthrough transcripts without involving deletions of cellular DNA.
Base Sequence↗