The FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation

The genome-scale data collected by the FANTOM4 collaborative research project are presented as an integrated web resource

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5′-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial releas

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions:a randomised controlled clinical trial in primary care

Background Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. Method This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. Discussion SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. Trial registration number: ISRCTN76503940. Date of Registration: 30.10.2019

Cadherin-10 maintains excitatory/inhibitory ratio through interactions with synaptic proteins

Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded byCDH10within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENTThe correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism.</jats:p

Stakeholder analysis for a maternal and newborn health project in Eastern Uganda

Background Based on the realization that Uganda is not on track to achieving Millennium Development Goals 4 and 5, Makerere University School of Public Health in collaboration with other partners proposed to conduct two community based maternal/newborn care interventions aimed at increasing access to health facility care through transport vouchers and use of community health workers to promote ideal family care practices. Prior to the implementation, a stakeholder analysis was undertaken to assess and map stakeholders’ interests, influence/power and position in relation to the interventions; their views regarding the success and sustainability; and how this research can influence policy formulation in the country. Methods A stakeholder analysis was carried out in March 2011 at national level and in four districts of Eastern Uganda where the proposed interventions would be conducted. At the national level, four key informant interviews were conducted with the ministry of health representative, Member of Parliament, and development partners. District health team members were interviewed and also engaged in a workshop; and at community level, twelve focus group discussions were conducted among women, men and motorcycle transporters. Results This analysis revealed that district and community level stakeholders were high level supporters of the proposed interventions but not drivers. At community level the mothers, their spouses and transporters were of low influence due to the limited funds they possessed. National level and district stakeholders believed that the intervention is costly and cannot be affordably scaled up. They advised the study team to mobilize and sensitize the communities to contribute financially from the start in order to enhance sustainability beyond the study period. Stakeholders believed that the proposed interventions will influence policy through modeling on how to improve the quality of maternal/newborn health services, male involvement, and improved accessibility of services. Conclusion Most of the stakeholders interviewed were supporters of the proposed maternal and newborn care intervention because of the positive benefits of the intervention. The analysis highlighted stakeholder concerns that will be included in the final project design and that could also be useful in countries of similar setting that are planning to set up programmes geared at increasing access to maternal and new born interventions. Key among these concerns was the need to use both human and financial resources that are locally available in the community, to address supply side barriers that influence access to maternal and child healthcare. Research to policy translation, therefore, will require mutual trust, continued dialogue and engagement of the researchers, implementers and policy makers to enable scale up.UKai

International home economics

The conference was planned to serve the interests of those who wish to work in home economics programs abroad and those who are concerned with the education of international students in the universities and colleges of the United States. Approximately 165 home economists from other states and from foreign countries I including the African and Latin American countries I participated in the conference.https://lib.dr.iastate.edu/card_reports/1026/thumbnail.jp

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Rhymes for wee sweethearts,

Colored ornamental borders.Mode of access: Internet