Giant cationic polyelectrolytes generated via electrochemical oxidation of single-walled carbon nanotubes

Previously, reduced single-walled carbon nanotube anions have been used for effective processing and functionalization. Here we report individually separate and distinct (that is, discrete) single-walled carbon nanotube cations, directly generated from a pure anode using a non-aqueous electrochemical technique. Cyclic voltammetry provides evidence for the reversibility of this nanoion electrochemisty, and can be related to the complex electronic density of states of the single-walled carbon nanotubes. Fixed potentiostatic oxidation allows spontaneous dissolution of nanotube cations ('nanotubium'); Raman spectroscopy and transmission electron microscopy show that sequential fractions are purified, separating amorphous carbon and short, defective single-walled carbon nanotubes, initially. The preparation of nanotubium, in principle, enables a new family of nucleophilic grafting reactions for single-walled carbon nanotubes, exploited here, to assemble nanotubes on amine-modified Si surfaces. Other nanoparticle polyelectrolyte cations may be anticipated

A Third Copy of the Down Syndrome Cell Adhesion Molecule ( Dscam ) Causes Synaptic and Locomotor Dysfunction in Drosophila

Down syndrome (DS) is caused by triplication of chromosome 21 (HSA21). It is characterised by intellectual disability and impaired motor coordination that arise from changes in brain volume, structure and function. However, the contribution of each HSA21 gene to these various phenotypes and to the causal alterations in neuronal and synaptic structure and function are largely unknown. Here we have investigated the effect of overexpression of the HSA21 gene DSCAM (Down syndrome cell adhesion molecule), on glutamatergic synaptic transmission and motor coordination, using Drosophila expressing three copies of Dscam1. Electrophysiological recordings of miniature and evoked excitatory junction potentials at the glutamatergic neuromuscular junction of Drosophila larvae showed that the extra copy of Dscam1 changed the properties of spontaneous and electrically-evoked transmitter release and strengthened short-term synaptic depression during high-frequency firing of the motor nerve. Behavioural analyses uncovered impaired locomotor coordination despite preserved gross motor function. This work identifies DSCAM as a candidate causative gene in DS that is sufficient to modify synaptic transmission and synaptic plasticity and cause a DS behavioural phenotype

Impaired Pre-Motor Circuit Activity and Movement in a Drosophila Model of KCNMA1-Linked Dyskinesia

BACKGROUND: Paroxysmal dyskinesias (PxDs) are characterized by involuntary movements and altered pre-motor circuit activity. Causative mutations provide a means to understand the molecular basis of PxDs. Yet in many cases, animal models harboring corresponding mutations are lacking. Here we utilize the fruit fly, Drosophila, to study a PxD linked to a gain-of-function (GOF) mutation in the KCNMA1/hSlo1 BK potassium channel. OBJECTIVES: We aimed to recreate the equivalent BK (big potassium) channel mutation in Drosophila. We sought to determine how this mutation altered action potentials (APs) and synaptic release in vivo; to test whether this mutation disrupted pre-motor circuit function and locomotion; and to define neural circuits involved in locomotor disruption. METHODS: We generated a knock-in Drosophila model using homologous recombination. We used electrophysiological recordings and calcium-imaging to assess AP shape, neurotransmission, and the activity of the larval pre-motor central pattern generator (CPG). We used video-tracking and automated systems to measure movement, and developed a genetic method to limit BK channel expression to defined circuits. RESULTS: Neuronal APs exhibited reduced width and an enhanced afterhyperpolarization in the PxD model. We identified calcium-dependent reductions in neurotransmitter release, dysfunction of the CPG, and corresponding alterations in movement, in model larvae. Finally, we observed aberrant locomotion and dyskinesia-like movements in adult model flies, and partially mapped the impact of GOF BK channels on movement to cholinergic neurons. CONCLUSION: Our model supports a link between BK channel GOF and hyperkinetic movements, and provides a platform to dissect the mechanistic basis of PxDs. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Charged Carbon Nanomaterials: Redox Chemistries of Fullerenes, Carbon Nanotubes, and Graphenes

Since the discovery of buckminsterfullerene over 30 years ago, sp2-hybridised carbon nanomaterials (including fullerenes, carbon nanotubes, and graphene) have stimulated new science and technology across a huge range of fields. Despite the impressive intrinsic properties, challenges in processing and chemical modification continue to hinder applications. Charged carbon nanomaterials (CCNs), formed via the reduction or oxidation of these carbon nanomaterials, facilitate dissolution, purification, separation, chemical modification, and assembly. This approach provides a compelling alternative to traditional damaging and restrictive liquid phase exfoliation routes. The broad chemistry of CCNs not only provides a versatile and potent means to modify the properties of the parent nanomaterial but also raises interesting scientific issues. This review focuses on the fundamental structural forms: buckminsterfullerene, single-walled carbon nanotubes, and single-layer graphene, describing the generation of their respective charged nanocarbon species, their interactions with solvents, chemical reactivity, specific (opto)electronic properties, and emerging applications

Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME

Expression of interfacial Seebeck coefficient through grain boundary engineering with multi-layer graphene nanoplatelets

Expression of energy filtering to boost thermoelectric performance through grain boundary engineering utilising graphene.</p

“Click-fluors”: triazole-linked saccharide sensors

A series of boronic acid-containing saccharide receptors was synthesised via copper catalysed azide–alkyne cycloaddition (CuAAC) reactions.</p

Impaired Pre-Motor Circuit Activity and Movement in a Drosophila Model of KCNMA1-Linked Dyskinesia.

BACKGROUND: Paroxysmal dyskinesias (PxDs) are characterized by involuntary movements and altered pre-motor circuit activity. Causative mutations provide a means to understand the molecular basis of PxDs. Yet in many cases, animal models harboring corresponding mutations are lacking. Here we utilize the fruit fly, Drosophila, to study a PxD linked to a gain-of-function (GOF) mutation in the KCNMA1/hSlo1 BK potassium channel. OBJECTIVES: We aimed to recreate the equivalent BK (big potassium) channel mutation in Drosophila. We sought to determine how this mutation altered action potentials (APs) and synaptic release in vivo; to test whether this mutation disrupted pre-motor circuit function and locomotion; and to define neural circuits involved in locomotor disruption. METHODS: We generated a knock-in Drosophila model using homologous recombination. We used electrophysiological recordings and calcium-imaging to assess AP shape, neurotransmission, and the activity of the larval pre-motor central pattern generator (CPG). We used video-tracking and automated systems to measure movement, and developed a genetic method to limit BK channel expression to defined circuits. RESULTS: Neuronal APs exhibited reduced width and an enhanced afterhyperpolarization in the PxD model. We identified calcium-dependent reductions in neurotransmitter release, dysfunction of the CPG, and corresponding alterations in movement, in model larvae. Finally, we observed aberrant locomotion and dyskinesia-like movements in adult model flies, and partially mapped the impact of GOF BK channels on movement to cholinergic neurons. CONCLUSION: Our model supports a link between BK channel GOF and hyperkinetic movements, and provides a platform to dissect the mechanistic basis of PxDs. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo

The CACCC-box binding protein erythroid Kruppel-like factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of the gene for a second KLF, basic Kruppel-like factor, or KLF3. We have now tested the in vivo role of KLF3 in erythroid cells by examining Klf3 knockout mice. KLF3-deficient adults exhibit a mild compensated anemia, including enlarged spleens, increased red pulp, and a higher percentage of erythroid progenitors, together with elevated reticulocytes and abnormal erythrocytes in the peripheral blood. Impaired erythroid maturation is also observed in the fetal liver. We have found that KLF3 levels rise as erythroid cells mature to become TER119(+). Consistent with this, microarray analysis of both TER119(-) and TER119(+) erythroid populations revealed that KLF3 is most critical at the later stages of erythroid maturation and is indeed primarily a transcriptional repressor. Notably, many of the genes repressed by KLF3 are also known to be activated by EKLF. However, the majority of these are not currently recognized as erythroid-cell-specific genes. These results reveal the molecular and physiological function of KLF3, defining it as a feedback repressor that counters the activity of EKLF at selected target genes to achieve normal erythropoiesis