Effectiveness and cost-effectiveness of community perinatal mental health services on access, experience, recovery/relapse and obstetric and neonate outcomes: the ESMI-II mixed-methods study.

Oct3/4, a hallmark of the earliest stages of embryogenesis, is expressed in undifferentiated embryonal carcinoma (EC) and embryonic stem (ES) cells. Oct3/4 gene expression is dependent on the promoter region, the proximal enhancer and the newly identified distal enhancer. We have analysed in vivo occupancy of these elements. In undifferentiated EC and ES cells, strong footprints were detected at specific sites of all three regulatory elements. These were promptly lost upon RA treatment in ES cells and in P19 EC cells, in parallel with sharply reduced Oct3/4 mRNA levels. Thus, the occupancy of regulatory elements is coupled with Oct3/4 expression, and RA treatment causes coordinated factor displacement, leading to extinction of gene activity. In F9 EC cells, footprint was first abolished at the proximal enhancer. However, this loss of binding site occupancy did not result in a decrease in Oct3/4 mRNA levels. The partial factor displacement seen in F9 EC cells, combined with the observation that EC and ES cells utilize the proximal and distal enhancers in differential manner, indicate the complex pattern of Oct3/4 gene regulation, which could reflect a cell type- and lineage-specific expression of the gene in vivo.

The mammalian endopeptidase, furin, is predominantly localized to the trans-Golgi network (TGN) at steady state. The localization of furin to this compartment seems to be the result of a dynamic process in which the protein undergoes cycling between the TGN and the plasma membrane. Both TGN localization and internalization from the plasma membrane are mediated by targeting information contained within the cytoplasmic domain of furin. Here, we report the results of a mutagenesis analysis aimed at identifying the source(s) of targeting information within the furin cytoplasmic domain. Our studies show that there are at least two cytoplasmic determinants that contribute to the steady-state localization and trafficking of furin. The first determinant corresponds to a canonical tyrosine-based motif, YKGL (residues 758-761), that functions mainly as an internalization signal. The second determinant consists of a strongly hydrophilic sequence (residues 766-783) that contains a large cluster of acidic residues (E and D) and is devoid of any tyrosine-based or di-leucine-based motifs. This second determinant is capable of conferring localization to the TGN as well as mediating internalization from the plasma membrane. Thus, these observations establish the existence of a novel, autonomous determinant distinct from sorting signals described previously.

Comparing the Hadlock fetal growth standard to the Eunice Kennedy Shriver National Institute of Child Health and Human Development racial/ethnic standard for the prediction of neonatal morbidity and small for gestational age

The zeta (zeta) chain plays a central role in T cell antigen receptor assembly and signal transduction. From previous work in murine T cell hybridomas we have inferred that the zeta subunit is limiting in receptor assembly. Partial receptors made in excess of zeta are assembled in the endoplasmic reticulum, transported through the Golgi, but then rapidly and efficiently degraded in lysosomes. zeta would therefore seem to play a unique role in targeting receptors from the Golgi to the cell surface. To determine directly whether zeta limits receptor assembly we have reconstituted a zeta-deficient T cell line by transfection of the murine zeta cDNA. Transfection results in restoration of expression of surface T cell receptor. In addition, increasing zeta expression results in a commensurate increase in the survival of previously excess subunits. This is reflected in an increased surface expression of complete receptors. Finally, transfection of the zeta cDNA fails to produce detectable zeta-eta heterodimers. The implications of these findings with regard to receptor assembly, and the relationship between zeta and eta, are discussed.

The cell surface protein repertoire needs to be regulated in response to changes in the extracellular environment. In this study, we investigate protein turnover of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p, in response to a change in extra-cellular copper levels. As Ctr1p mediates high affinity uptake of copper into the cell, modulation of its expression is expected to be involved in copper homeostasis. We demonstrate that Ctr1p is a stable protein when cells are grown in low concentrations of copper, but that exposure of cells to high concentrations of copper (10 microM) triggers degradation of cell surface Ctr1p. This degradation appears to be specific for Ctr1p and does not occur with another yeast plasma membrane protein tested. Internalization of some Ctr1p can be seen when cells are exposed to copper. However, yeast mutant strains defective in endocytosis (end3, end4 and chc1-ts) and vacuolar degradation (pep4) exhibit copper-dependent Ctr1p degradation, indicating that internalization and delivery to the vacuole is not the principal mechanism responsible for degradation. In addition, a variant Ctr1p with a deletion in the cytosolic tail is not internalized upon exposure of cells to copper, but is nevertheless degraded. These observations indicate that proteolysis at the plasma membrane most likely explains copper-dependent turnover of Ctr1p and point to the existence of a novel pathway in yeast for plasma membrane protein turnover.

50 years ago in the journal of pediatrics: Why Johnny can’t read: Fact or fallacy

Soluble gonadotropin receptors of the rat ovary

Using a scheme for selecting mutants of Saccharomyces cerevisiae with abnormalities of iron metabolism, we have identified a gene, AFT1, that mediates the control of iron uptake. AFT1 encodes a 78 kDa protein with a highly basic amino terminal domain and a glutamine-rich C-terminal domain, reminiscent of transcriptional activators. The protein also contains an amino terminal and a C-terminal region with 10% His residues. A dominant mutant allele of this gene, termed AFT1-1up, results in high levels of ferric reductase and ferrous iron uptake that are not repressed by exogenous iron. The increased iron uptake is associated with enhanced susceptibility to iron toxicity. These effects may be explained by the failure of iron to repress transcription of FRE1, FRE2 and FET3. FRE1 and FRE2 encode plasma membrane ferric reductases, obligatory for ferric iron assimilation, and FET3 encodes a copper-dependent membrane-associated oxidase required for ferrous iron uptake. Conversely, a strain with interruption of the AFT1 gene manifests low ferric reductase and ferrous iron uptake and is susceptible to iron deprivation, because of deficient expression of FRE1 and negligible expression of FRE2 and FET3. Thus, AFT1 functions to activate transcription of target genes in response to iron deprivation and thereby plays a central role in iron homeostasis.

Communicating More than Content: Formal Features of Children's Television Programs

Regulation of ovarian gonadotropin receptors and LH bioactivity during the estrous cycle

Unified standard for fetal growth velocity: the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies

IUBMB LifeEarly View SPECIAL ISSUE Mammalian iron sulfur cluster biogenesis and human diseases Nunziata Maio, Corresponding Author Nunziata Maio maion@mail.nih.gov orcid.org/0000-0002-6225-6058 Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA Correspondence Nunziata Maio, Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, 20892 Bethesda, MD, USA. Email: maion@mail.nih.govSearch for more papers by this authorTracey A. Rouault, Tracey A. Rouault Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USASearch for more papers by this author Nunziata Maio, Corresponding Author Nunziata Maio maion@mail.nih.gov orcid.org/0000-0002-6225-6058 Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA Correspondence Nunziata Maio, Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, 20892 Bethesda, MD, USA. Email: maion@mail.nih.govSearch for more papers by this authorTracey A. Rouault, Tracey A. Rouault Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USASearch for more papers by this author First published: 31 January 2022 https://doi.org/10.1002/iub.2597 Funding information: Intramural Research Program of the National Institutes of Health Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

Background Specialist community perinatal mental health teams support women diagnosed with moderate to severe psychiatric difficulties in pregnancy or postnatally. These teams are being expanded across the UK, and there is considerable international interest in this model of care. However, not all women access these teams, and many are instead supported by community mental health services that do not specialise in the perinatal period. Aims To explore perinatal women’s experiences of specialist perinatal versus generic non-perinatal community mental health support. Methods Semi-structured interviews were conducted with 36 women diagnosed with perinatal mental health difficulties who were supported in the community either by a specialist perinatal or general non-perinatal mental health service. Data were analysed thematically. Results Women felt that specialist perinatal and non-perinatal services alike were under-resourced and somewhat too narrow in their remit, but reported positive experiences across both settings. They particularly valued the specialist expertise offered by perinatal teams, but also valued greater continuity of care over a longer period, which some non-perinatal teams provided. Conclusions The findings suggest that women who experience perinatal mental health difficulties value specialist perinatal expertise, but that general, non-perinatal teams may also have advantages for some. Further research into optimal care arrangements is merited.

Internal Working Models, Trust, and Sharing among Foragers

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