Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts

Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4, TP63, OVOL1, CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such as LHX4 and SYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development

Site-specific spectroscopic measurement of spin and charge in (LuFeO3)m/(LuFe2O4)1 multiferroic superlattices

Interface materials offer a means to achieve electrical control of ferrimagnetism at room temperature as was recently demonstrated in (LuFeO3)m/(LuFe2O4)1 superlattices. A challenge to understanding the inner workings of these complex magnetoelectric multiferroics is the multitude of distinct Fe centres and their associated environments. This is because macroscopic techniques characterize average responses rather than the role of individual iron centres. Here, we combine optical absorption, magnetic circular dichroism and first-principles calculations to uncover the origin of high-temperature magnetism in these superlattices and the charge-ordering pattern in the m = 3 member. In a significant conceptual advance, interface spectra establish how Lu-layer distortion selectively enhances the Fe2+ → Fe3+ charge-transfer contribution in the spin-up channel, strengthens the exchange interactions and increases the Curie temperature. Comparison of predicted and measured spectra also identifies a non-polar charge ordering arrangement in the LuFe2O4 layer. This site-specific spectroscopic approach opens the door to understanding engineered materials with multiple metal centres and strong entanglement.Fil: Fan, Shiyu. University of Tennessee; Estados UnidosFil: Das, Hena. Cornell University; Estados UnidosFil: Rébola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; ArgentinaFil: Smith, Kevin. University of Tennessee; Estados UnidosFil: Mundy, Julia. Harvard University; Estados Unidos. Cornell University; Estados UnidosFil: Brooks, Charles. Cornell University; Estados UnidosFil: Holtz, Megan E.. Cornell University; Estados UnidosFil: Muller, David A.. Cornell University; Estados UnidosFil: Fennie, Craig J.. Cornell University; Estados UnidosFil: Ramesh, Ramamoorthy. Lawrence Berkeley National Laboratory; Estados Unidos. University of California at Berkeley; Estados UnidosFil: Schlom, Darrell G.. Cornell University; Estados UnidosFil: McGill, Stephen. National High Magnetic Field Laboratory; Estados UnidosFil: Musfeldt, Janice L.. University of Tennessee; Estados Unido

Reducing alcohol harms whilst minimising impact on hospitality businesses: ‘Sweetspot’ policy options

Background During COVID-19, hospitality businesses (e.g. bars, restaurants) were closed/restricted whilst off-sales of alcohol increased, with health consequences. Post-covid, governments face lobbying to support such businesses, but many health services remain under pressure. We appraised ‘sweetspot’ policy options: those with potential to benefit public services and health, whilst avoiding or minimising negative impact on the hospitality sector. Methods We conducted rapid non-systematic evidence reviews using index papers, citation searches and team knowledge to summarise the literature relating to four possible ‘sweetspot’ policy areas: pricing interventions (9 systematic reviews (SR); 14 papers/reports); regulation of online sales (1 SR; 1 paper); place-shaping (2 SRs; 18 papers/reports); and violence reduction initiatives (9 SRs; 24 papers/reports); and led two expert workshops (n = 11). Results Interventions that raise the price of cheaper shop-bought alcohol appear promising as ‘sweetspot’ policies; any impact on hospitality is likely small and potentially positive. Restrictions on online sales such as speed or timing of delivery may reduce harm and diversion of consumption from on-trade to home settings. Place-shaping is not well-supported by evidence and experts were sceptical. Reduced late-night trading hours likely reduce violence; evidence of impact on hospitality is scant. Other violence reduction initiatives may modestly reduce harms whilst supporting hospitality, but require resources to deliver multiple measures simultaneously in partnership. Conclusions Available evidence and expert views point to regulation of pricing and online sales as having greatest potential as ‘sweetspot’ alcohol policies, reducing alcohol harm whilst minimising negative impact on hospitality businesses

Reducing alcohol harms whilst minimising impact on hospitality businesses: ‘Sweetspot’ policy options

Background During COVID-19, hospitality businesses (e.g. bars, restaurants) were closed/restricted whilst off-sales of alcohol increased, with health consequences. Post-covid, governments face lobbying to support such businesses, but many health services remain under pressure. We appraised ‘sweetspot’ policy options: those with potential to benefit public services and health, whilst avoiding or minimising negative impact on the hospitality sector. Methods We conducted rapid non-systematic evidence reviews using index papers, citation searches and team knowledge to summarise the literature relating to four possible ‘sweetspot’ policy areas: pricing interventions (9 systematic reviews (SR); 14 papers/reports); regulation of online sales (1 SR; 1 paper); place-shaping (2 SRs; 18 papers/reports); and violence reduction initiatives (9 SRs; 24 papers/reports); and led two expert workshops (n = 11). Results Interventions that raise the price of cheaper shop-bought alcohol appear promising as ‘sweetspot’ policies; any impact on hospitality is likely small and potentially positive. Restrictions on online sales such as speed or timing of delivery may reduce harm and diversion of consumption from on-trade to home settings. Place-shaping is not well-supported by evidence and experts were sceptical. Reduced late-night trading hours likely reduce violence; evidence of impact on hospitality is scant. Other violence reduction initiatives may modestly reduce harms whilst supporting hospitality, but require resources to deliver multiple measures simultaneously in partnership. Conclusions Available evidence and expert views point to regulation of pricing and online sales as having greatest potential as ‘sweetspot’ alcohol policies, reducing alcohol harm whilst minimising negative impact on hospitality businesses

West Virginia Woodland Welcome Wagon: Design, Implementation, and Evaluation in Three Priority Areas

The majority of West Virginia\u27s forested land is owned by private family forest owners. It is essential that natural resources professionals work with and support these individuals as they establish their ideal woodlands and sustain ecosystem services, which are at risk from parcelization and fragmentation. The West Virginia Woodland Welcome Wagon was carried out in three priority areas to connect new landowners with natural resources professionals. Over the course of 6 months, absentee landowners, landowners with fewer than 50 acres, and those interested in socializing with other woodland owners were found to be more likely to participate in the project

Reducing alcohol harms whilst minimising impact on hospitality businesses: ‘Sweetspot’ policy options

Background: During COVID-19, hospitality businesses (e.g. bars, restaurants) were closed/restricted whilst off-sales of alcohol increased, with health consequences. Post-covid, governments face lobbying to support such businesses, but many health services remain under pressure. We appraised ‘sweetspot’ policy options: those with potential to benefit public services and health, whilst avoiding or minimising negative impact on the hospitality sector. Methods: We conducted rapid non-systematic evidence reviews using index papers, citation searches and team knowledge to summarise the literature relating to four possible ‘sweetspot’ policy areas: pricing interventions (9 systematic reviews (SR); 14 papers/reports); regulation of online sales (1 SR; 1 paper); place-shaping (2 SRs; 18 papers/reports); and violence reduction initiatives (9 SRs; 24 papers/reports); and led two expert workshops (n = 11). Results: Interventions that raise the price of cheaper shop-bought alcohol appear promising as ‘sweetspot’ policies; any impact on hospitality is likely small and potentially positive. Restrictions on online sales such as speed or timing of delivery may reduce harm and diversion of consumption from on-trade to home settings. Place-shaping is not well-supported by evidence and experts were sceptical. Reduced late-night trading hours likely reduce violence; evidence of impact on hospitality is scant. Other violence reduction initiatives may modestly reduce harms whilst supporting hospitality, but require resources to deliver multiple measures simultaneously in partnership. Conclusions: Available evidence and expert views point to regulation of pricing and online sales as having greatest potential as ‘sweetspot’ alcohol policies, reducing alcohol harm whilst minimising negative impact on hospitality businesses

Site-specific spectroscopic measurement of spin and charge in (LuFeO3)m/(LuFe2O4)1 multiferroic superlattices.

Interface materials offer a means to achieve electrical control of ferrimagnetism at room temperature as was recently demonstrated in (LuFeO3)m/(LuFe2O4)1 superlattices. A challenge to understanding the inner workings of these complex magnetoelectric multiferroics is the multitude of distinct Fe centres and their associated environments. This is because macroscopic techniques characterize average responses rather than the role of individual iron centres. Here, we combine optical absorption, magnetic circular dichroism and first-principles calculations to uncover the origin of high-temperature magnetism in these superlattices and the charge-ordering pattern in the m = 3 member. In a significant conceptual advance, interface spectra establish how Lu-layer distortion selectively enhances the Fe2+ →  Fe3+ charge-transfer contribution in the spin-up channel, strengthens the exchange interactions and increases the Curie temperature. Comparison of predicted and measured spectra also identifies a non-polar charge ordering arrangement in the LuFe2O4 layer. This site-specific spectroscopic approach opens the door to understanding engineered materials with multiple metal centres and strong entanglement

Site-specific spectroscopic measurement of spin and charge in (LuFeO3)m/(LuFe2O4)1 multiferroic superlattices.

Interface materials offer a means to achieve electrical control of ferrimagnetism at room temperature as was recently demonstrated in (LuFeO3)m/(LuFe2O4)1 superlattices. A challenge to understanding the inner workings of these complex magnetoelectric multiferroics is the multitude of distinct Fe centres and their associated environments. This is because macroscopic techniques characterize average responses rather than the role of individual iron centres. Here, we combine optical absorption, magnetic circular dichroism and first-principles calculations to uncover the origin of high-temperature magnetism in these superlattices and the charge-ordering pattern in the m = 3 member. In a significant conceptual advance, interface spectra establish how Lu-layer distortion selectively enhances the Fe2+ →  Fe3+ charge-transfer contribution in the spin-up channel, strengthens the exchange interactions and increases the Curie temperature. Comparison of predicted and measured spectra also identifies a non-polar charge ordering arrangement in the LuFe2O4 layer. This site-specific spectroscopic approach opens the door to understanding engineered materials with multiple metal centres and strong entanglement

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.publishe