Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36–54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351–727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia.     

Triploidy—Observations in 154 Diandric Cases

Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0–1,4%).     

Using Effort to Measure Reward Value of Faces in Children with Autism

According to one influential account, face processing atypicalities in autism reflect reduced reward value of faces, which results in limited attention to faces during development and a consequent failure to acquire face expertise. Surprisingly, however, there is a paucity of work directly investigating the reward value of faces for individuals with autism and the evidence for diminished face rewards in this population remains equivocal. In the current study, we measured how hard children with autism would work to view faces, using an effortful key-press sequence, and whether they were sensitive to the differential reward value of attractive and unattractive faces. Contrary to expectations, cognitively able children with autism did not differ from typically developing children of similar age and ability in their willingness to work to view faces. Moreover, the effort expended was strongly positively correlated with facial attractiveness ratings in both groups of children. There was also no evidence of atypical reward values for other, less social categories (cars and inverted faces) in the children with autism. These results speak against the possibility that face recognition difficulties in autism are explained by atypical reward value of faces.     

Wild gregarious settlements of Ostrea edulis in a semi‐enclosed sea lough: a case study for unassisted restoration

Ostrea edulis was once prolific throughout Europe and considered as the continent's native oyster. However, O. edulis currently exists in small fragmented assemblages where natural unaided recovery is rarely encountered. This research identified the small semi‐enclosed sea Lough of Strangford on the northeast coast of Northern Ireland as one of the few locations within Europe where the native oyster displayed gregarious natural rejuvenation. On close examination, four influential parameters appeared to assist in concentrated settlement; raised topographical cultch formations, shell coverage, the number of fecund in situ adults, and site protection. If these components were to be combined and managed as part of reintroduction and restoration initiatives, high‐density settlements and self‐sustaining populations may be possible. The research also identified that unregulated harvesting of intertidal O. edulis assemblages has the potential to seriously hinder natural recoveries. Indeed, the findings suggest that a review of policy in regards to intertidal hand gathering is necessary. However, naturally occurring high‐density settlements recorded during this research should be inspirational to all involved in the restoration of the native oyster.