Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry The hidden phase boundaries that emerge demarcate vacancy-network polymorphs with very different micropore characteristics Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiencyGenome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease Here I discuss the scientific, technical and ethical aspects of using CRISPR clustered regularly interspaced short palindromic repeats technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges Genome editing is-or will soon be-in the clinic for several diseases, with more applications under development The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic diseaseBacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2 Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200nbsp;kilobases kb, including a genome of 735nbsp;kb, which is-to our knowledge-the largest phage genome to be described to date Thirty-five genomes were manually curated to completion circular and no gaps Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs tRNAs, tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystemsMultiple sclerosis is a chronic inflammatory disease of the CNS1 Astrocytes contribute to the pathogenesis of multiple sclerosis2, but little is known about the heterogeneity of astrocytes and its regulation Here we report the analysis of astrocytes in multiple sclerosis and its preclinical model experimental autoimmune encephalomyelitis EAE by single-cell RNA sequencing in combination with cell-specific Ribotag RNA profiling, assay for transposase-accessible chromatin with sequencing ATAC-seq, chromatin immunoprecipitation with sequencing ChIP-seq, genome-wide analysis of DNA methylation and in vivo CRISPR-Cas9-based genetic perturbations We identified astrocytes in EAE and multiple sclerosis that were characterized by decreased expression of NRF2 and increased expression of MAFG, which cooperates with MAT2α to promote DNA methylation and represses antioxidant and anti-inflammatory transcriptional programs Granulocyte-macrophage colony-stimulating factor GM-CSF signalling in astrocytes drives the expression of MAFG and MAT2α and pro-inflammatory transcriptional modules, contributing to CNS pathology in EAE and, potentially, multiple sclerosis Our results identify candidate therapeutic targets in multiple sclerosisLevels of gene expression underpin organismal phenotypes1,2, but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown1,2 Here we assayed gene expression in rice Oryza sativa3, and used phenotypic selection analysis to estimate the type and strength of selection on the levels of more than 15,000nbsp;transcripts4,5 Variation in most transcripts appears nearly neutral or under very weak stabilizing selection in wet paddy conditions with median standardized selection differentials near zero, but selection is stronger under drought conditions Overall, more transcripts are conditionally neutral 283 than are antagonistically pleiotropic6 004, and transcripts that display lower levels of expression and stochastic noise7-9 and higher levels of plasticity9 are under stronger selection Selection strength was further weakly negatively associated with levels of cis-regulation and network connectivity9 Our multivariate analysis suggests that selection acts on the expression of photosynthesis genes4,5, but that the efficacy of selection is genetically constrained under drought conditions10 Drought selected for earlier flowering11,12 and a higher expression of OsMADS18 Os07g0605200, which encodes a MADS-box transcription factor and is a known regulator of early flowering13-marking this gene as a drought-escape gene11,12  https//wwwselleckchemcom/products/caspofungin-acetatehtml  The ability to estimate selection strengths provides insights into how selection can shape molecular traits at the core of gene actionThe mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions that range from decision-making to consciousness1 Here we report that a homologue of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, also exists in a reptile-the Australian bearded dragon Pogona vitticeps In Pogona, the claustrum underlies the generation of sharp waves during slow-wave sleep The sharp waves, together with superimposed high-frequency ripples2, propagate to the entire neighbouring pallial dorsal ventricular ridge DVR Unilateral or bilateral lesions of the claustrum suppress the production of sharp-wave ripples during slow-wave sleep in a unilateral or bilateral manner, respectively, but do not affect the regular and rapidly alternating sleep rhythm that is characteristic of sleep in this species3 The claustrum is thus not involved in the generation of the sleep rhythm itself Tract tracing revealed that the reptilian claustrum projects widely to a variety of forebrain areas, including the cortex, and that it receives converging inputs from, among others, areas of the mid- and hindbrain that are known to be involved in wake-sleep control in mammals4-6