ZMYM2 inhibits NANOG-mediated reprogramming.

Background: NANOG is a homeodomain-containing transcription factor which forms one of the hubs in the pluripotency network and plays a key role in the reprogramming of somatic cells and epiblast stem cells to naïve pluripotency.  Studies have found that NANOG has many interacting partners and some of these were shown to play a role in its ability to mediate reprogramming. In this study, we set out to analyse the effect of NANOG interactors on the reprogramming process. Methods: Epiblast stem cells and somatic cells were reprogrammed to naïve pluripotency using MEK/ERK inhibitor PD0325901, GSK3β inhibitor CHIR99021 and Leukaemia Inhibitory Factor (together termed 2i Plus LIF). Zmym2 was knocked out using the CRISPR/Cas9 system or overexpressed using the PiggyBac system. Reprogramming was quantified after ZMYM2 deletion or overexpression, in diverse reprogramming systems. In addition, embryonic stem cell self renewal was quantified in differentiation assays after ZMYM2 removal or overexpression. Results: In this work, we identified ZMYM2/ZFP198, which physically associates with NANOG as a key negative regulator of NANOG-mediated reprogramming of both epiblast stem cells and somatic cells. In addition, ZMYM2 impairs the self renewal of embryonic stem cells and its overexpression promotes differentiation. Conclusions: We propose that ZMYM2 curtails NANOG's actions during the reprogramming of both somatic cells and epiblast stem cells and impedes embryonic stem cell self renewal, promoting differentiation.This study was supported by the Wellcome Trust through a Wellcome Trust Fellowship to J.C.R.S. [101861], Wellcome Trust Studentship to M.L. [079249], and a core funding grant jointly with the Medical Research Council (MRC) to the Wellcome-MRC Cambridge Stem Cell Institute [079249]

Current preconception care practice in the Netherlands — An evaluation study among birth care professionals

Objective: To evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. Methods: We have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. Findings: Respondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. Key conclusion: Birth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. Implications for practice:To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.</p

Routine outcome monitoring en benchmarking: hoe kunnen we behandelresultaten op een zorgvuldige manier vergelijken?

Contains fulltext : 157216.pdf (publisher's version ) (Open Access)Achtergrond: Het structureel meten van de resultaten van een behandeling in de geestelijke gezondheidszorg en het vergelijken daarvan tussen instellingen helpen om inzicht te krijgen in het effect van behandelingen in de reguliere praktijk. Doel: Geven van een overzicht van de kwesties die van belang zijn bij het vergelijken van instellingen. Methode: Analyseren van documentatie en beleidsinformatie over en praktijkervaring met routine outcome monitoring (rom). Resultaten: We beschrijven knelpunten die kunnen ontstaan bij het vergelijken van instellingen en formuleren oplossingsrichtingen voor deze knelpunten. Daarbij staat centraal dat het werken met rom een groeiproces is, waarbij men experimenteert met verschillende oplossingsrichtingen en op basis van ervaringen definitieve keuzes maakt. Conclusie: Het is leerzaam om instellingen te vergelijken, zowel onderling als met 'best practices' (benchmarking). Instellingen verschillen echter in cliëntenpopulaties, meetprocedures en instrumentarium. Een zinvolle vergelijking is op termijn toch mogelijk.5 p

Vortex Motion Noise in Micrometre-Sized Thin Films of the Amorphous Nb0.7Ge0.3 Weak-Pinning Superconductor

We report high-resolution measurements of voltage (V) noise in the mixed state of micrometre-sized thin films of amorphous Nb0.7Ge0.3, which is a good representative of weak-pinning superconductors. There is a remarkable difference between the noise below and above the irreversibility field Birr. Below Birr, in the presence of measurable pinning, the noise at small applied currents resembles shot noise, and in the regime of flux flow at larger currents decreases with increasing voltage due to a progressive ordering of the vortex motion. At magnetic fields B between Birr and the upper critical field Bc2 flux flow is present already at vanishingly small currents. In this regime the noise scales with (1-B/Bc2)^2 V^2 and has a frequency (f) spectrum of 1/f type. We interpret this noise in terms of the properties of strongly driven depinned vortex systems at high vortex density.Comment: 8 pages, 5 figures, version accepted for publication in PR

Periconception maternal folate status and human embryonic cerebellum growth trajectories: The Rotterdam predict study

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032-0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/ CRL:β = 0.011mm/mm, 95%CI = 0.005-0.017, p