Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene ...expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.
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•miR-155 is highly induced during mouse and human Th17 cell differentiation•Jarid2 and miR-155 are epistatic in Th17 and Treg cells•Jarid2 is required to recruit PRC2 to genomic sites in Th17 cells•Direct targets of PRC2 in Th17 cells include Il22, Il10, Il9, and Atf3
miR-155 is known to promote inflammatory Th17 cell responses, but the mechanism has been unclear. Escobar et al. find that miR-155 promotes cytokine expression in Th17 cells by repressing Jarid2 to relieve Polycomb-mediated gene silencing.
The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, ...the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (γδ) T cells, and natural killer T (NKT) cells.
Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. The country needs novel, large-scale, and sustainable interventions to improve ...hypertension control. We report the 12 month follow-up results of a cluster randomized feasibility trial in Hung Yen province, Vietnam, which evaluated the feasibility and acceptability of two community-based interventions to improve hypertension control: a "storytelling" and a didactic intervention.
The storytelling intervention included stories in the patients' own words about coping with hypertension and didactic content about the importance of healthy lifestyle behaviors in controlling elevated blood pressure levels. The didactic intervention included only didactic content, which were general recommendations for managing several important risk factors for hypertension and other non-communicable diseases. The storytelling intervention was delivered by two DVDs three months apart; the didactic intervention included only one DVD. The trial was conducted in patients with poorly controlled hypertension from 4 communes (communities), which were equally randomized to the two interventions.
The mean age of the 160 patients was 66 years and 54% were men. Between baseline enrollment and the 12 month follow-up, mean systolic blood pressure declined by 10.8 mmHg (95% CI: 6.5-14.9) in the storytelling group and by 5.8 mmHg (95% CI: 1.6-10.0) in the didactic content group. The storytelling group also experienced more improvement in several health behaviors, including increased levels of physical activity and reduced consumption of salt and alcohol.
We observed considerable long-term beneficial effects of both interventions, especially of our storytelling intervention, among patients with inadequately controlled hypertension. A large scale randomized trial should more systematically compare the short and long-term effectiveness of the two interventions in controlling hypertension.
ClinicalTrials.gov: NCT02483780.
In addition to its use in the fertilizer and chemical industries1, ammonia is currently seen as a potential replacement for carbon-based fuels and as a carrier for worldwide transportation of ...renewable energy2. Implementation ofthis vision requires transformation of the existing fossil-fuel-based technology for NH3 production3 to a simpler, scale-flexible technology, such as the electrochemical lithium-mediated nitrogen-reduction reaction3,4. This provides a genuine pathway from N2 to ammonia, but it is currently hampered by limited yield rates and low efficiencies4-12. Here we investigate the role of the electrolyte in this reaction and present a high-efficiency, robust process that is enabled by compact ionic layering in the electrode-electrolyte interface region. The interface is generated by a high-concentration imide-based lithium-salt electrolyte, providing stabilized ammonia yield rates of 150 ± 20 nmol s-1 cm-2 and a current-to-ammonia efficiency that is close to 100%. The ionic assembly formed at the electrode surface suppresses the electrolyte decomposition and supports stable N2 reduction. Our study highlights the interrelation between the performance of the lithium-mediated nitrogen-reduction reaction and the physicochemical properties of the electrode-electrolyte interface. We anticipate that these findings will guide the development of a robust, high-performance process for sustainable ammonia production.
Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ...ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to express mature miR-290 miRNAs and have selective aberrant overexpression of Hoxa, Hoxb, Hoxc, and Hoxd genes essential for body plan patterning during embryogenesis, but they do not undergo a full differentiation program. Introduction of mature miR-291 into DCR−/− ESCs restores Hox gene silencing. This was attributed to the unexpected regulation of Polycomb-mediated gene targeting by miR-291. We identified the methyltransferase Ash1l as a pivotal target of miR-291 mediating this effect. Collectively, our data shed light on the role of Dicer in ESC homeostasis by revealing a facet of molecular regulation by the miR-290 family.
•Silencing of Hox genes in ESCs is defective in the absence of Dicer•A member of the miR-290 family is sufficient to rescue the Hox gene-silencing defect•There is widespread Polycomb deregulation in Dicer-deficient ESCs•miR-290 can restore Polycomb localization by regulating Ash1l
Muljo, Lenardo, and colleagues find that in Dicer-deficient mouse embryonic stem cells (mESCs), there is reduced Polycomb Repressive Complex 2 binding and increased gene expression at many loci, including the Hoxa–Hoxd gene cluster. These defects in mESC-fate programming can be rescued by the miR-290 family and to a lesser extent by knockdown of Ash1l, a putative target of miR-290.
Studies of the ammonia oxidation reaction (AOR) for the synthesis of nitrite and nitrate (NO2/3−) have been limited to a small number of catalytic materials, majorly Pt based. As the demand for ...nitrate‐based products such as fertilisers continues to grow, exploration of alternative catalysts is needed. Herein, 19 metals immobilised as particles on carbon fibre electrodes were tested for their catalytic activity for the ammonia electrooxidation to NO2/3− under alkaline conditions (0.1 m KOH). Nickel‐based electrodes showed the highest overall NO2/3− yield with a rate of 5.0±1.0 nmol s−1 cm−2, to which nitrate contributed 62±8 %. Cu was the only catalyst that enabled formation of nitrate, at a rate of 1.0±0.4 nmol s−1 cm−2, with undetectable amounts of nitrite produced. Previously unexplored in this context, Fe and Ag also showed promise and provided new insights into the mechanisms of the process. Ag‐based electrodes showed strong indications of activity towards NH3 oxidation in electrochemical measurements but produced relatively low NO2/3− yields, suggesting the formation of alternate oxidation products. NO2/3− production over Fe‐based electrodes required the presence of dissolved O2 and was more efficient than with Ni on longer timescales. These results highlight the complexity of the AOR mechanism and provide a broad set of catalytic activity and nitrate versus nitrite yield data, which might guide future development of a practical process for the distributed sustainable production of nitrates and nitrites at low and medium scales.
Into the deep: Sustainable synthesis of nitrites and nitrates can be achieved by electrocatalytic ammonia oxidation. However, our understanding of the materials that are catalytically active for this reaction is limited. The present work serves to broaden our knowledge by conducting a survey of different metal‐based catalysts for their activity towards ammonia electrooxidation to NO2/3−. Among the materials tested, nickel, copper, iron and silver showed the greatest promise.
Ethnic minority women (EMW) living in mountainous areas of northern Vietnam have disproportionately high infant and maternal mortality rates as a result of low maternal health knowledge, poverty, and ...remoteness from low-capacity health centers.
The objective of this study was to describe the protocol for the development and evaluation of the mMom intervention, which is an integrated mobile health (mHealth) system designed to improve maternal and infant health knowledge, and behavior among women in remote areas of Thai Nguyen, Vietnam.
This project featured the following four phases: (1) development of an mHealth platform integrated into the existing health management information system in partnership with the provincial health department; (2) ethnographic fieldwork and intervention content development; (3) intervention piloting and implementation; and (4) evaluation of the intervention's impact on participants' maternal health knowledge, behavior, and interactions with the health system.
The mMom project development process resulted in the following: (1) the successful development of the mMom system, including the mHealth platform hardware and integration, the intervention plan and content, and the monitoring and evaluation framework; (2) the piloting and implementation of the intervention as planned; and (3) the implementation of the monitoring and evaluation framework components.
This protocol outlines the development of the mMom intervention and describes critical next steps in understanding the impact of the intervention on participants and the wider health system in Thai Nguyen province, Vietnam.
Vietnam is experiencing an epidemiologic transition with an increased prevalence of non-communicable diseases. Novel, large-scale, effective, and sustainable interventions to control hypertension in ...Vietnam are needed. We report the results of a cluster-randomized feasibility trial at 3 months follow-up conducted in Hung Yen province, Vietnam, designed to evaluate the feasibility and acceptability of two community-based interventions to improve hypertension control: a "storytelling" intervention, "We Talk about Our Hypertension," and a didactic intervention.
The storytelling intervention included stories about strategies for coping with hypertension, with patients speaking in their own words, and didactic content about the importance of healthy lifestyle behaviors including salt reduction and exercise. The didactic intervention included only didactic content. The storytelling intervention was delivered by two DVDs at 3-month intervals; the didactic intervention included only one installment. The trial was conducted in four communes, equally randomized to the two interventions.
The mean age of the 160 study patients was 66 years, and 54% were men. Most participants described both interventions as understandable, informative, and motivational. Between baseline and 3 months, mean systolic blood pressure declined by 8.2 mmHg (95% CI 4.1-12.2) in the storytelling group and by 5.5 mmHg (95% CI 1.4-9.5) in the didactic group. The storytelling group also reported a significant increase in hypertension medication adherence.
Both interventions were well accepted in several rural communities and were shown to be potentially effective in lowering blood pressure. A large-scale randomized trial is needed to compare the effectiveness of the two interventions in controlling hypertension.
ClinicalTrials.gov, NCT02483780.
Abstract The major goal of this study was to perform an in depth characterization of the “gene signature” of human FoxP3+ T regulatory cells (Tregs). Highly purified Tregs and T conventional cells ...(Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro , were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3 , IKZF2 , and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes ( RTKN2 , LAYN , UTS2 , CSF2RB , TRIB1 , F5 , CECAM4 , CD70 , ENC1 and NKG7 ) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs.
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