Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are resistant to PB. Previous animal ...studies have shown that in postnatal day P7 mice pups with ischemic stroke induced by unilateral carotid ligation, the tyrosine receptor kinase B (TrkB) antagonist ANA12 (N-2-(hexahydro-2-oxo-1H-azepin-3-yl)aminocarbonylphenyl-benzobthiophene-2-carboxamide, 5 mg/kg) improved the efficacy of PB in reducing seizure occurrence. To meet optimal standards of effectiveness, a wider range of ANA12 doses must be tested. Here, using the unilateral carotid ligation model, we tested the effectiveness of higher doses of ANA12 (10 and 20 mg/kg) on the ability of PB to reduce seizure burden, ameliorate cell death (assessed by Fluoro-Jade staining), and affect neurodevelopment (righting reflex, negative geotaxis test, open field test). We found that a single dose of ANA12 (10 or 20 mg/kg) given 1 h after unilateral carotid ligation in P7 pups reduced seizure burden and neocortical and striatal neuron death without impairing developmental reflexes. In conclusion, ANA12 at a range of doses (10-20 mg/kg) enhanced PB effectiveness for the treatment of perinatal ischemia-related seizures, suggesting that this agent might be a clinically safe and effective adjunctive agent for the treatment of pharmacoresistant neonatal seizures.
Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional ...regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in
gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and β-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and β-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts.
Introduction: Integrated Child Development Services (ICDS) scheme provides a wide range of health, nutrition and education services to children, women and adolescent girls. Maternal satisfaction ...usually influences service uptake and utilization. Therefore, in addition to coverage, the quality of services provided and end-user satisfaction need to be assessed. Material and Methods: A cross-sectional community-level study was conducted in the urban block of the Patiala district in Punjab. A total of 54 AWCs were selected from a sample frame of 222 by applying a systematic random sampling technique. From each selected AWC, 20 mothers of registered beneficiaries (0-6 years) were randomly selected for interview. The data collected was entered and analysed using SPSS version 22. Results: The present study revealed that most of the Anganwadis (87.19%) were regularly open for the provision of various ICDS services. However, only 48.02% of children received supplementary nutrition from AWC regularly. Only 32.36% of children who were sick were referred by AWW. Satisfaction with quantity and quality of food served was found to be 61% and 45.90% among mothers, respectively. Conclusion: It was concluded that there is a need to improve the quality of services to overcome the problem of under-utilisation of services despite the wide coverage of ICDS services; regular orientation and training courses for AWWs should be conducted to ensure better service delivery to all beneficiaries.
Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional ...regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and beta-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and beta-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses beta-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/beta-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and beta-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts.
Global investors have been storming out of the yen for months in anticipation of last week's move by the Bank of Japan, bringing the currency's decline to more than 25% against the dollar since late ...September. On Tuesday, the dollar climbed as high as 99.67 yen, but by midday in New York it had slipped back to 99.08 yen, down from 99.37 yen on Monday, when the yen hit its weakest level since April 2009. Japanese investors are pouring money into the market for European sovereign debt, these investors and analysts said, sending yields on some countries' bonds to record lows. Despite the recent turmoil in European bonds, Japan's investors are attracted to the market's large size and the stability of the euro. The Bank of Japan's moves also are being felt in currency markets. On Friday, the Mexican peso rallied against the U.S. dollar even after disappointing U.S. jobs data. Usually in that situation, the peso would fall versus the dollar or stay flat because the two countries' economies are closely linked, said Sebastien Galy, a strategist at Societe Generale SA in New York.
Some Japanese investors are retreating from the yen-denominated domestic government-bond market, the main target of the Bank of Japan's expanded asset-purchase program, to snatch up higher yields ...elsewhere. Japanese institutions hold some 630 trillion yen ($6.458 trillion) in domestic government bonds, Bank of Japan data show.
PDF
