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Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy, and seizures. NGLY1's activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development. [Display omitted] • NGLY1 neurons develop ProteoStat-positive aggregates that can be partially rescued • Profiling protein aggregates unveils links to other neurodegenerative diseases • NGLY1 phenotypes appear to be predominantly observed in neurons Manole et al. employ cutting-edge techniques including laser capture microscopy to scrutinize the protein aggregates accumulating in NGLY1-deficient neurons. Their study unveils a significant enrichment of specific proteins associated with neurodegenerative diseases, providing novel insights into the pathological mechanisms underlying NGLY1 deficiency and shedding light on potential therapeutic targets. [ABSTRACT FROM AUTHOR]

High interest in the detection and quantification of (elevated) intracellular zinc levels in tumor cells has been aroused due to the crucial physiological roles and the pathophysiological implications of zinc. Despite their diverse applications, benzo[1,2- b :4,5- b′ ]difuran (BDF) derivatives as a fluorescent Zn(II) probe in living cells have not been reported. By careful chemical design of molecular components, we prepared and fully characterized a new amphiphilic BDF-based fluorophore. A series of experiments were carried out to test the cytotoxicity and cellular uptake behavior in human cancer derived HeLa cells. The ligand fluorescence is strongly quenched upon the addition of Zn(II) ions. The high cell membrane permeability, low cytotoxicity and significant fluorescence quenching behavior render this ligand very promising for in vitro detection of Zn(II) ions in biological systems. [ABSTRACT FROM AUTHOR]

Abstract: A new phase of the compound, Na3ZnB5O10, crystallizes in orthorhombic space group Pbca (No. 61) with lattice constants a =7.8923(4)Å, b =12.2437(7)Å, c =18.0636(11)Å, Z =8. The Na3ZnB5O10 structure exhibits that the isolated B5O10 groups are bridged by ZnO4 tetrahedra and NaO n (n =5,7) polyhedra through the vertex oxygen atoms to form an infinite three-dimensional structure. Functional groups in the sample were identified by IR spectrum. Na3ZnB5O10 has a phase transition, and exhibits a short-wavelength absorption onset below 190nm. [Copyright &y& Elsevier]

Abstract: An efficient and practical synthesis of unsymmetrical diarylmethanes has been achieved from the dehydration of arenes with benzyl alcohols in the presence of catalytic amount of InCl3·4H2O/acetylacetone. [Copyright &y& Elsevier]