A global reference for human genetic variation

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

Distributed Coherent Aperture Radar Enabled by Microwave Photonics

Distributed Coherent Aperture Radar (DCAR) utilizes multiple separated antenna apertures to emit signals in the same space area, realizing spatial coherent synthesis of electro-magnetic waves. Such a flexible radar system has advantages such as higher resolution, greater radar power, and lower cost. Combined with microwave photonic technologies, which have merits in wideband signal generation, transmission and procession, the DCAR has a comprehensive and better performance. This paper introduces a microwave photonics-based high-resolution distributed coherent aperture radar that was proposed by researchers of Tsinghua University. Taking advantages of microwave photonic technology, a group of wideband orthogonal phase-coded linear frequency modulation waves is generated in the coherence-on-receive mode, with the frequency ranging from 8.5 GHz to 11.5 GHz, all with phase coding under a bit rate of 0.5 Gbps. The orthogonality of the signals is nearly 30 dB, and the range resolution is better than 0.05 m. While in the full coherence mode, the transmitted waveforms can be flexibly switched to the wideband coherent linear frequency modulation waves, and the full coherent synthesis can be realized. The waveforms generated by the proposed system can meet the waveform requirements of the DCAR in different operation modes. In the experiment, full coherence is achieved with two sets of radars, resulting a signal- to-noise ratio gain of 8.3 dB

An Interleaved Broadband Photonic ADC Immune to Channel Mismatches Capable for High-Speed Radar Imaging

A dual channel interleaved broadband subsampling photonic analog-to-digital converter (ADC) immune to channel mismatches capable for high-speed radar imaging is presented. Through modeling as a combination of photonic subsampling front-end and interleaved Nyquist sampling electronic ADC back-end, the mechanism of photonic interleaved subsampling of broadband signal and the appearance of spurious components caused by channel mismatches are explained. The effect of these spurious components on radar detecting is revealed. Through fractional Fourier domain filtering, the spurious components are eliminated, making the SNR of received X-band chirp signal (8–11.9 GHz) improved from 13.26 to 23.88 dB. Thanks to its downsampling and interleaved architecture, the demands of bandwidth, sampling rate, and storage depth for post electronics are all lowered, making it capable for high-speed and mass data receiving. In the experiment, inverse synthetic aperture radar imaging is performed characterized with range and cross range resolution of 4.9 and 7.9 cm. The false target due to the spurious component is distinguished through band-pass filtering in matched fractional Fourier domain

Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion

Summary: The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers

Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy

Abstract The CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery