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Alkyne complexes with vicinal substitution by a Lewis acid and a Lewis base at the coordinated alkyne are prospective frustrated Lewis pairs exhibiting a particular mutual distance and, hence, a specific activation potential. In this contribution, investigations on the generation of a W(II) alkyne complex bearing a phosphine as Lewis base and a carbenium group as Lewis acid are presented. Independently on potential substrates added, an intramolecular cyclisation product was always isolated. A subsequent deprotonation step led to an unprecedented side-on λ 5 -phosphinyne complex, which is interpreted as highly zwitterionic according to visible absorption spectroscopy supported by TD-DFT. Low-temperature 31 P NMR and EPR spectroscopic measurements combined with time-dependent IR-spectroscopic monitoring provided insights in the mechanism of the cyclisation reaction. Decomposition of the multicomponent IR spectra by multivariate curve resolution and a kinetic hard-modelling approach allowed the derivation of kinetic parameters. Assignment of the individual IR spectra to potential intermediates was provided by DFT calculations. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.Children with familial risk (FR) of dyslexia and children with early language delay are known to be at risk for later language and literacy difficulties. However, research addressing long-term outcomes in children with both risk factors is scarce. This study tracked FR and No-FR children identified as late talkers at 2 years of age and reports development from 4;6 through 6 years. We examined the possible effects of FR-status and late talking (LT) status, respectively, on language skills at school entry, and whether FR-status moderated the associations between 4;6-year and 6-year language scores. Results indicated an effect of LT status on language at both ages, while FR status affected language skills at 6 years only. The interaction between LT and FR statuses was not significant, implying that LT status affected language skills independently of the child's FR status. A proportion of late talkers developed typical language at 6 years of age, while some FR children with typical vocabulary skills in toddlerhood had emerging developmental language disorder by school entry. FR status had a moderating effect on the association between expressive grammar at ages 4;6 and 6 years. [https://www.selleckchem.com/products/l-histidine-monohydrochloride-monohydrate.html LHistidinemonohydrochloridemonohydrate] Possible explanations for the effect of FR status on language skills are discussed. We highlight limitations in the study size and suggest how these preliminary findings can inform future research. © 2020 The Authors. Dyslexia published by John Wiley &amp; Sons Ltd.Intrinsically disordered regions in proteins (IDRs) mediate many disease-related protein-protein interactions. However, the unfolded character and continuous conformational changes of IDRs make them difficult to target for therapeutic purposes. Here we show that a designed peptide based on the disordered p53 linker domain can be used for targeting a partner IDR from the anti-apoptotic iASPP protein, promoting apoptosis of cancer cells. The p53 linker forms a hairpin-like structure with its two termini in close proximity. We designed a peptide derived from the disordered termini without the hairpin, termed p53 LinkTer. The LinkTer peptide bound the disordered RT loop of iASPP with the same affinity as the parent p53 Linker peptide, and inhibited the p53-iASPP interaction in vitro. The LinkTer peptide showed increased stability to proteolysis, penetrated cancer cells, caused nuclei shrinkage and decreased cells viability. We conclude that a designed peptide comprising only the IDR from a peptide sequence can be an improved inhibitor since it binds its target protein without the need for pre-folding, paving the way for therapeutic targeting of IDRs. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.An cross-reactive optical sensor array based on poly(p-phenyleneethynylene)s (PPEs) determines Edman degradated amino acids. We report a sensor array composed of three anionic PPEs P1-P3 , and their electrostatic complexes with metal ions (Fe 2+ , Cu 2+ , Co 2+ ). We recorded distinct fluorescence intensity response patterns as "fingerprints" of this chemical tongue toward standard phenylthiohydantoin (PTH) amino acids - degradation products of the Edman process. These "fingerprints" were converted into canonical scores by linear discrimination analysis (LDA), which differentiates all of the PTH-amino acids. This array discriminates PTH-amino acid residues degraded from an oligopeptide through Edman sequencing. This approach is complementary to chromatography approaches which rely on mass spectrometry; our array offers the advantage of simplicity. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.PURPOSES The aim of the pharmacovigilance (PV) process is to bring together all the much-needed information about various aspects of product safety or, in particular, the safety and vigilance of drugs as pharmaceutical products. This study aimed to investigate and provide an overview on the current situation and activities of the national PV centers in Arab countries. METHODS A cross sectional study was conducted between March and May in 2018. The current survey was adopted and modified from a study that used the questionnaire designed by the World Health Organization Collaborating Centre for International Drug Monitoring. The national PV centers of 22 Arab countries were invited to participate in this study. Descriptive analyses were conducted utilizing the analysis services provided by SurveyMonkey. RESULTS In total of, 15 countries responded to our invitation (response rate 68%). Most Arab countries started their PV program in the last decade, with Palestine implementing its program in 2017. Among the respondents, nine (60%) were members of the WHO International Drug Monitoring Program and were all users of the software provided by the WHO Uppsala Monitoring Center (VigiFlow or VigiBase), except Sudan. In 2017, a total of 27 502 reports were received by the centers in the studied countries, ranging from three reports received in Lebanon to a total of 7362 reports received by the national program of Algeria. CONCLUSIONS An improvement was noticed among the national PV programs in the Arab countries. However, a considerable difference still exists among the countries in terms of the implementation and practice of PV. © 2020 John Wiley &amp; Sons Ltd.