How to find and diagnose a CDG due to defective N-glycosylation

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Solutions of ionic liquids with diverse aliphatic and aromatic solutes – Phase behavior and potentials for applications:A review article

This article principally reviews our research related to liquid–liquid and solid–liquid phase behavior of imidazolium- and phosphonium-based ionic liquids, mainly having bistriflamide ([NTf2]−) or triflate ([OTf]−) anions, with several aliphatic and aromatic solutes (target molecules). The latter include: (i) diols and triols: 1,2-propanediol, 1,3-propanediol and glycerol; (ii) polymer poly(ethylene glycol) (PEG): average molecular mass 200, 400 and 2050 – PEG200 (liquid), PEG400 (liquid) and PEG2050 (solid), respectively; (iii) polar aromatic compounds: nicotine, aniline, phenolic acids (vanillic, ferulic and caffeic acid,), thymol and caffeine and (iv) non-polar aromatic compounds (benzene, toluene, p-xylene). In these studies, the effects of the cation and anion, cation alkyl chain and PEG chain lengths on the observed phase behaviors were scrutinized. Thus, one of the major observations is that the anion – bistriflamide/triflate – selection usually had strong, sometimes really remarkable effects on the solvent abilities of the studied ionic liquids. Namely, in the case of the hydrogen-bonding solutes, the ionic liquids with the triflate anion generally exhibited substantially higher solubility than those having the bistriflamide anion. Nevertheless, with the aromatic compounds the situation was the opposite – in most of the cases it was the bistriflamide anion that favoured solubility. Moreover, our other studies confirmed the ability of PEG to dissolve both polar and non-polar aromatic compounds. Therefore, two general possibilities of application of alternative, environmentally acceptable, solvents of tuneable solvent properties appeared. One is to use homogeneous mixtures of two ionic liquids having [NTf2]− and [OTf]− anions as mixed solvents. The other, however, envisages the application of homogeneous and heterogeneous (PEG + ionic liquid) solutions as tuneable solvents for aromatic solutes. Such mixed solvents have potential applications in separation of the aforesaid target molecules from their aqueous solutions or in extraction from original matrices. From the fundamental point of view the phase equilibrium studies reviewed herein and the diversity of the pure compounds – ionic liquids and target molecules – represent a good base for the discussion of interactions between the molecules that exist in the studied solutions

Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease : Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial

The supplementary material is available in the electronic version of this article: http://dx.doi.org/10.3233/JAD-170560. The study was sponsored by TauRx Therapeutics (Singapore). We thank Lon Schneider and Howard Feldman for their contribution to the Scientific Advisory Board. We gratefully acknowledge study investigators and the generosity of study participants. Authors’ disclosures available online (http://j-alz.com/manuscript disclosures/17-0560r3).Peer reviewedPublisher PD

High incidence of Noonan Syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation

Article first published online: 21 AUG 2015Abstract not availableKitiwan Rojnueangnit ... Christopher P. Barnett ... et al

Oncolytic Measles Virotherapy and Opposition to Measles Vaccination

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination

Grammatical gender and linguistic relativity: A systematic review

Many languages assign nouns to a grammatical gender class, such that ‘bed’ might be assigned masculine gender in one language (e.g. Italian) but feminine gender in another (e.g. Spanish). In the context of research assessing the potential for language to influence thought (the linguistic relativity hypothesis), a number of scholars have investigated whether grammatical gender assignment ‘rubs off’ on concepts themselves, such that Italian speakers might conceptualise beds as more masculine than Spanish speakers. We systematically reviewed 43 pieces of empirical research examining grammatical gender and thought, which together tested 5,895 participants. We classified the findings in terms of their support for this hypothesis, and assessed the results against parameters previously identified as potentially influencing outcomes. Overall, we found that support was strongly task- and context-dependent, and rested heavily on outcomes that have clear and equally-viable alternative explanations. We also argue that it remains unclear whether grammatical gender is in fact a useful tool for investigating relativity

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Abstract Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. </jats:sec

Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation