Adaptive functions of structural variants in human brain development.

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV map in a population of 562 rhesus macaques, verified by in-house benchmarks of eight macaque genomes with long-read sequencing and another one with genome assembly. This map indicates stronger selective constrains on inversions at regulatory regions, suggesting a strategy for prioritizing them with the most important functions. Accordingly, we identified 75 human-specific inversions and prioritized them. The top-ranked inversions have substantially shaped the human transcriptome, through their dual effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof of concept, we linked APCDD1, located on one of these inversions and down-regulated specifically in humans, to neuronal maturation and cognitive ability. We thus highlight inversions in shaping the human uniqueness in brain development.

The failure behavior of coal-rock combined body under compression-shear loading.

As shallow coal reserves continue to deplete rapidly, deep mining has become an unavoidable course of action. In the process of deep coal mining, affected by blasting, mining, and excavation, the coal-rock interface often encounters the action of compression-shear composite load. The interface crack directly affects the stability of the coal-rock structure. Uniaxial compression experiments have been conducted on rock and coal-like material with pre-existing interfacial oblique cracks to study the crack propagation criterion of the rock and coal-like material interface. An image acquisition system is used to record the surface speckle field of the whole process of specimen failure. The strain fields and stress intensity factor of the sample at different times are obtained by digital image correlation. At the same time, the stress field near the crack tip is calculated. The results show that with the increase of loading, two strains of localization bands are formed on the surface of the specimen. One of the strain-localized bands starts at the lower tip of the prefabricated crack and propagates along the vertical interface. The other starts at the upper tip of the prefabricated damage and propagates along the interface direction. It can be seen that the lower tip of the prefabricated crack enters into the crack fracture process zone earlier than the upper tip. The strain localization band narrows gradually with the load increase, and then macro cracks appear. The initiation of two tips is suitable for different fracture criteria. The lower tip is dominated by the maximum circumferential tensile stress, and the upper tip is dominated by shear stress. The specimens eventually fracture along the interface. The evolution of the strain field during the failure process of rock and coal-like material can reflect the generation and propagation of the crack.

STellaris: a web server for accurate spatial mapping of single cells based on spatial transcriptomics data.

Single-cell RNA sequencing (scRNA-seq) provides insights into gene expression heterogeneities in diverse cell types underlying homeostasis, development and pathological states. However, the loss of spatial information hinders its applications in deciphering spatially related features, such as cell-cell interactions in a spatial context. Here, we present STellaris (https://spatial.rhesusbase.com), a web server aimed to rapidly assign spatial information to scRNA-seq data based on their transcriptomic similarity with public spatial transcriptomics (ST) data. STellaris is founded on 101 manually curated ST datasets comprising 823 sections across different organs, developmental stages and pathological states from humans and mice. STellaris accepts raw count matrix and cell type annotation of scRNA-seq data as the input, and maps single cells to spatial locations in the tissue architecture of properly matched ST section. Spatially resolved information for intercellular communications, such as spatial distance and ligand-receptor interactions (LRIs), are further characterized between annotated cell types. Moreover, we also expanded the application of STellaris in spatial annotation of multiple regulatory levels with single-cell multiomics data, using the transcriptome as a bridge. STellaris was applied to several case studies to showcase its utility of adding value to the ever-growing scRNA-seq data from a spatial perspective.

A Human-Specific De Novo Gene Promotes Cortical Expansion and Folding.

Newly originated de novo genes have been linked to the formation and function of the human brain. However, how a specific gene originates from ancestral noncoding DNAs and becomes involved in the preexisting network for functional outcomes remains elusive. Here, a human-specific de novo gene, SP0535, is identified that is preferentially expressed in the ventricular zone of the human fetal brain and plays an important role in cortical development and function. In human embryonic stem cell-derived cortical organoids, knockout of SP0535 compromises their growth and neurogenesis. In SP0535 transgenic (TG) mice, expression of SP0535 induces fetal cortex expansion and sulci and gyri-like structure formation. The progenitors and neurons in the SP0535 TG mouse cortex tend to proliferate and differentiate in ways that are unique to humans. SP0535 TG adult mice also exhibit improved cognitive ability and working memory. Mechanistically, SP0535 interacts with the membrane protein Na+ /K+ ATPase subunit alpha-1 (ATP1A1) and releases Src from the ATP1A1-Src complex, allowing increased level of Src phosphorylation that promotes cell proliferation. Thus, SP0535 is the first proven human-specific de novo gene that promotes cortical expansion and folding, and can function through incorporating into an existing conserved molecular network.

De novo genes with an lncRNA origin encode unique human brain developmental functionality.

Human de novo genes can originate from neutral long non-coding RNA (lncRNA) loci and are evolutionarily significant in general, yet how and why this all-or-nothing transition to functionality happens remains unclear. Here, in 74 human/hominoid-specific de novo genes, we identified distinctive U1 elements and RNA splice-related sequences accounting for RNA nuclear export, differentiating mRNAs from lncRNAs, and driving the origin of de novo genes from lncRNA loci. The polymorphic sites facilitating the lncRNA-mRNA conversion through regulating nuclear export are selectively constrained, maintaining a boundary that differentiates mRNAs from lncRNAs. The functional new genes actively passing through it thus showed a mode of pre-adaptive origin, in that they acquire functions along with the achievement of their coding potential. As a proof of concept, we verified the regulations of splicing and U1 recognition on the nuclear export efficiency of one of these genes, the ENSG00000205704, in human neural progenitor cells. Notably, knock-out or over-expression of this gene in human embryonic stem cells accelerates or delays the neuronal maturation of cortical organoids, respectively. The transgenic mice with ectopically expressed ENSG00000205704 showed enlarged brains with cortical expansion. We thus demonstrate the key roles of nuclear export in de novo gene origin. These newly originated genes should reflect the novel uniqueness of human brain development.

Dynamic Effect of Shaped Charge Blasting and Its Application in Coal Seam Permeability Enhancement.

The dynamic effect of shaped charge blasting and its application in coal seam permeability enhancement have been investigated. Comparative experiments of shaped charge blasting and conventional blasting to fracture the concrete are carried out. Then, the propagation characteristics of explosion stress waves under shaped charge blasting and conventional blasting are analyzed by ANSYS/LS-DYNA. Finally, the fracture mechanical model of shaped charge blasting is established. The experimental results show that the width of the four main cracks formed after conventional blasting is 0.3 cm, while the width of the cracks in the energy accumulation direction after shaped charge blasting is 1.1 cm and the width of that in the vertical energy accumulation direction is 0.4 cm. The numerical simulation results show that the crushing area after shaped charge blasting is "dumbbell type", and the area is smaller than that of conventional blasting. However, the cracking area is "spindle type", and the development of the fracture degree is better than that of conventional blasting. In addition, shaped charge blasting is used to improve the permeability of coal seams. The results show that shaped charge blasting effectively improves the permeability and gas extraction rate of coal seams.

Experimental investigation into the effects of composition and microstructure on the tensile properties and failure characteristics of different gypsum rocks.

The present work investigated the differences in the composition and internal microstructure of four types gypsum rock-fiber gypsum, transparent gypsum, alabaster, and ordinary gypsum by X-ray fluorescence spectrometry, X-ray diffraction, scanning electron microscope and Brazilian split test, and analyzed its effects on the tensile strength and fracture characteristics of gypsum rock. For alabaster, fiber gypsum, transparent gypsum, and ordinary gypsum, CaSO4·2H2O is the main component with 72.78%, 72.72%, 72.57%, and 71.51% content, and tensile strength of 1.79, 2.22, 3.22, and 4.35 MPa, respectively. In addition, the fracture line is arc-shaped, vertical, and zigzag for fiber gypsum, ordinary and transparent gypsums, and alabaster, respectively. On the microscopic level, fiber gypsum has an evident striated structure while the gradual increased pore development for alabaster, transparent gypsum, and ordinary gypsum. Gypsum rock has an obvious layered crystal structure with the increase of CaSO4·2H2O, contributing to the phenomenon with a larger grain size and lower tensile strength. In addition, the number of particles for alabaster, transparent gypsum, and ordinary gypsum increased in turn, while their particle size decreased uniformly, indicating that the lower CaSO4·2H2O content, the more sufficient energy accumulation and release. This paper can provide a theoretical basis for the analysis of the mechanical properties of rocks with different mineral composition and contribute to the design for different ore grades mining.

Public health, climate, and economic impacts of desulfurizing jet fuel.

In jurisdictions including the US and the EU ground transportation and marine fuels have recently been required to contain lower concentrations of sulfur, which has resulted in reduced atmospheric SO(x) emissions. In contrast, the maximum sulfur content of aviation fuel has remained unchanged at 3000 ppm (although sulfur levels average 600 ppm in practice). We assess the costs and benefits of a potential ultra-low sulfur (15 ppm) jet fuel standard ("ULSJ"). We estimate that global implementation of ULSJ will cost US$1-4bn per year and prevent 900-4000 air quality-related premature mortalities per year. Radiative forcing associated with reduction in atmospheric sulfate, nitrate, and ammonium loading is estimated at +3.4 mW/m(2) (equivalent to about 1/10th of the warming due to CO(2) emissions from aviation) and ULSJ increases life cycle CO(2) emissions by approximately 2%. The public health benefits are dominated by the reduction in cruise SO(x) emissions, so a key uncertainty is the atmospheric modeling of vertical transport of pollution from cruise altitudes to the ground. Comparisons of modeled and measured vertical profiles of CO, PAN, O(3), and (7)Be indicate that this uncertainty is low relative to uncertainties regarding the value of statistical life and the toxicity of fine particulate matter.