Evidence for large superhumps in TX Col and V4742 Sgr

Since the discovery of the largest positive superhump period in TV Col, we have started a program to search for superhumps in CVs with large orbital periods. Here, we summarize preliminary results of TX Col and V4742 Sgr. TX Col is an intermediate polar with a 5.7-h orbital period. V4742 Sgr is a recent nova with no known periods. CCD unfiltered continuous photometry of these 2 objects was carried out during 56 nights in 2002-3. In TX Col, in addition to the orbital period of 5.7 h, we found peaks at 7.1 h and 5.0 h. These are interpreted as positive and negative superhumps correspondingly, although the effects of the quasi-periodic oscillations at about 2 h were not taken into consideration. In the light curve of V4742 Sgr 2 long periods are detected -- 6.1 and 5.4 h as well as a short-term period at 1.6 h. This result suggests that V4742 Sgr is an intermediate polar candidate and a permanent superhump system with a large orbital period (5.4 h) and a superhump period excess of 13 percent. If these results are confirmed, TX Col, V4742 Sgr and TV Col form a group of intermediate polars with extremely large superhump periods. There seems to be now growing evidence that superhumps can occur in intermediate polars with long orbital periods, which is very likely inconsistent with the theoretical prediction that superhumps can only occur in systems with mass ratios below 0.33. Alternatively, if the mass ratio in these systems is nevertheless below the theoretical limit, they should harbour undermassive secondaries and massive white dwarfs, near the Chandrasekhar limit, which would make them excellent candidates for progenitors of supernovae type Ia.Comment: 9 pages, 8 figures, 3 sty files, To appear in the proceedings of IAU JD5, `White Dwarfs: Galactic and Cosmological Probes', eds. Ed Sion, Stephane Vennes and Harry Shipman, Full abstract in pape

Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders

Kainate receptors (KARs) are glutamate-gated cation channels with diverse roles in the central nervous system. Bi-allelic loss of function of the KAR-encoding gene GRIK2 causes a nonsyndromic neurodevelopmental disorder (NDD) with intellectual disability and developmental delay as core features. The extent to which mono-allelic variants in GRIK2 also underlie NDDs is less understood because only a single individual has been reported previously. Here, we describe an additional eleven individuals with heterozygous de novo variants in GRIK2 causative for neurodevelopmental deficits that include intellectual disability. Five children harbored recurrent de novo variants (three encoding p.Thr660Lys and two p.Thr660Arg), and four children and one adult were homozygous for a previously reported variant (c.1969G>A [p.Ala657Thr]). Individuals with shared variants had some overlapping behavioral and neurological dysfunction, suggesting that the GRIK2 variants are likely pathogenic. Analogous mutations introduced into recombinant GluK2 KAR subunits at sites within the M3 transmembrane domain (encoding p.Ala657Thr, p.Thr660Lys, and p.Thr660Arg) and the M3-S2 linker domain (encoding p.Ile668Thr) had complex effects on functional properties and membrane localization of homomeric and heteromeric KARs. Both p.Thr660Lys and p.Thr660Arg mutant KARs exhibited markedly slowed gating kinetics, similar to p.Ala657Thr-containing receptors. Moreover, we observed emerging genotype-phenotype correlations, including the presence of severe epilepsy in individuals with the p.Thr660Lys variant and hypomyelination in individuals with either the p.Thr660Lys or p.Thr660Arg variant. Collectively, these results demonstrate that human GRIK2 variants predicted to alter channel function are causative for early childhood development disorders and further emphasize the importance of clarifying the role of KARs in early nervous system development.Genetics of disease, diagnosis and treatmen

Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders (vol 108, pg 1692, 2021)

Neurolog

How do dual long-acting bronchodilators prevent exacerbations of chronic obstructive pulmonary disease?

Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting b2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaledcorticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus productionwith impairedmucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into thismanuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease. © 2017 by the American Thoracic Society