Carbon nanotubes as substrates for molecular spiropyran-based switches

We present a joint theory–experiment study investigating the excitonic absorption of spiropyran-functionalized carbon nanotubes. The functionalization is promising for engineering switches on a molecular level, since spiropyrans can be reversibly switched between two different conformations, inducing a distinguishable and measurable change of optical transition energies in the substrate nanotube. Here, we address the question of whether an optical read-out of such a molecular switch is possible. Combining density matrix and density functional theory, we first calculate the excitonic absorption of pristine and functionalized nanotubes. Depending on the switching state of the attached molecule, we observe a red-shift of transition energies by about 15 meV due to the coupling of excitons with the molecular dipole moment. Then we perform experiments measuring the absorption spectrum of functionalized carbon nanotubes for both conformations of the spiropyran molecule. We find good qualitative agreement between the theoretically predicted and experimentally measured red-shift, confirming the possibility for an optical read-out of the nanotube-based molecular switch

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Contribution of the land sector to a 1.5 °C world

Acknowledgements The analysis in this study was guided by the valuable feedback and recommendations of expert consultations and interviews, and we extend our gratitude to all those individuals who contributed to our research and analysis: Jeff Atkins (Virginia Commonwealth University), Jonah Busch (Earth Innovation Institute), Peter Ellis (The Nature Conservancy), Jason Funk (Center for Carbon Removal), Trisha Gopalakrishna (The Nature Conservancy), Alan Kroeger (Climate Focus), Bernice Lee (Chatham House), Donna Lee (Climate and Land Use Alliance), Simon Lewis (University College London), Guy Lomax (The Nature Conservancy), Dann Mitchell (University of Bristol), Raoni Rajão (University of Minas Gerais), Joeri Rogelj (IIASA), Carl-Friedrich Schleussner (Climate Analytics), Paul West (University of Minnesota), Graham Wynne (Prince of Wales International Sustainability Unit), Ana Yang (Children’s Investment Fund Foundation) and Dan Zarin (Climate and Land Use Alliance). A special thank you to Esther Chak and Mary-Jo Valentino (Imaginary Office) for designing the figures in this study. This work was generously supported by the Children’s Investment Fund Foundation and the authors’ institutions and funding sources.Peer reviewedPostprin

Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci

Background & aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource. Methods: We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses. Results: We provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application. Conclusions: We provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue