Comprehensive Analysis of Transcript Start Sites in Ly49 Genes Reveals an Unexpected Relationship with Gene Function and a Lack Of Upstream Promoters

Comprehensive analysis of the transcription start sites of the Ly49 genes of C57BL/6 mice using the oligo-capping 5′-RACE technique revealed that the genes encoding the “missing self” inhibitory receptors, Ly49A, C, G, and I, were transcribed from multiple broad regions in exon 1, in the intron1/exon2 region, and upstream of exon -1b. Ly49E was also transcribed in this manner, and uniquely showed a transcriptional shift from exon1 to exon 2 when NK cells were activated in vitro with IL2. Remarkably, a large proportion of Ly49E transcripts was then initiated from downstream of the translational start codon. By contrast, the genes encoding Ly49B and Q in myeloid cells, the activating Ly49D and H receptors in NK cells, and Ly49F in activated T cells, were predominantly transcribed from a conserved site in a pyrimidine-rich region upstream of exon 1. An ∼200 bp fragment from upstream of the Ly49B start site displayed tissue-specific promoter activity in dendritic cell lines, but the corresponding upstream fragments from all other Ly49 genes lacked detectable tissue-specific promoter activity. In particular, none displayed any significant activity in a newly developed adult NK cell line that expressed multiple Ly49 receptors. Similarly, no promoter activity could be found in fragments upstream of intron1/exon2. Collectively, these findings reveal a previously unrecognized relationship between the pattern of transcription and the expression/function of Ly49 receptors, and indicate that transcription of the Ly49 genes expressed in lymphoid cells is achieved in a manner that does not require classical upstream promoters

Possible association between moderate intellectual disability and weight gain in valproic acid–treated patients with epilepsy

Yukiko Tanamachi,1 Junji Saruwatari,1 Madoka Noai,1 Ryoko Kamihashi,1 Hiromi Soraoka,1 Yuki Yoshimori,1 Naoki Ogusu,1 Kentaro Oniki,1 Norio Yasui-Furukori,2 Takateru Ishitsu,3,4 Kazuko Nakagawa1,5 1Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan; 3Kumamoto Saishunso National Hospital, Koshi, Japan; 4Kumamoto Ezuko Ryoiku Iryo Center, Kumamoto, Japan; 5Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan Background: Although patients with moderate intellectual disability (ID) are known to have higher rates of being overweight and obese than those without ID, there are no current data regarding the relationship between ID and weight gain in epilepsy patients treated with valproic acid (VPA). Patients and methods: The possible association between moderate ID and an overweight status at the time of initiation of VPA therapy (baseline) was investigated using a logistic regression analysis in 143 patients with epilepsy. Among the 119 nonoverweight patients at baseline, the longitudinal association between moderate ID and the weight status during VPA therapy was retrospectively examined using a Cox hazards regression analysis and the generalized estimating equations approach, while also paying careful attention to associations with other patient characteristics. Results: The proportion of patients with moderate ID was 52.4% among the 143 study subjects. The presence of moderate ID was not associated with an overweight status at baseline (P=0.762). Among the nonoverweight patients at baseline, 16 subjects were newly diagnosed as being overweight during treatment with VPA (3.6±2.1 years). The presence of moderate ID was significantly associated with the incidence of an overweight status after starting VPA therapy (adjusted hazard ratio =6.72, P=0.007). The patient age at baseline and treatment with co-administered carbamazepine, clobazam, and zonisamide significantly influenced the degree of weight fluctuation during VPA therapy among the patients with moderate ID (P<0.001, P<0.001, P=0.002, and P=0.028, respectively), whereas only patient age at baseline affected this parameter among the patients without moderate ID (P=0.022). Conclusion: The present findings suggest that the weight status should be carefully monitored in VPA-treated patients with moderate ID, especially those receiving other co-administered antiepileptic drugs that facilitate weight gain, such as carbamazepine. Keywords: overweight, weight status, obesity, antiepileptic drug, longitudinal analysis&nbsp

Science Applications of Phased Array Radars

Abstract Phased array radars (PARs) are a promising observing technology, at the cusp of being available to the broader meteorological community. PARs offer near-instantaneous sampling of the atmosphere with flexible beam forming, multifunctionality, and low operational and maintenance costs and without mechanical inertia limitations. These PAR features are transformative compared to those offered by our current reflector-based meteorological radars. The integration of PARs into meteorological research has the potential to revolutionize the way we observe the atmosphere. The rate of adoption of PARs in research will depend on many factors, including (i) the need to continue educating the scientific community on the full technical capabilities and trade-offs of PARs through an engaging dialogue with the science and engineering communities and (ii) the need to communicate the breadth of scientific bottlenecks that PARs can overcome in atmospheric measurements and the new research avenues that are now possible using PARs in concert with other measurement systems. The former is the subject of a companion article that focuses on PAR technology while the latter is the objective here.Department of Defense (DoD)Department of Energy (DOE)National Aeronautics and Space Administration (NASA)National Ocean and Atmospheric Administration (NOAA)National Science Foundation (NSF