Cell biology of stem cells: an enigma of asymmetry and self-renewal

Stem cells present a vast, new terrain of cell biology. A central question in stem cell research is how stem cells achieve asymmetric divisions to replicate themselves while producing differentiated daughter cells. This hallmark of stem cells is manifested either strictly during each mitosis or loosely among several divisions. Current research has revealed the crucial roles of niche signaling, intrinsic cell polarity, subcellular localization mechanism, asymmetric centrosomes and spindles, as well as cell cycle regulators in establishing self-renewing asymmetry during stem cell division. Much of this progress has benefited from studies in model stem cell systems such as Drosophila melanogaster neuroblasts and germline stem cells and mammalian skin stem cells. Further investigations of these questions in diverse types of stem cells will significantly advance our knowledge of cell biology and allow us to effectively harness stem cells for therapeutic applications

Change point analysis of histone modifications reveals epigenetic blocks linking to physical domains

Histone modification is a vital epigenetic mechanism for transcriptional control in eukaryotes. High-throughput techniques have enabled whole-genome analysis of histone modifications in recent years. However, most studies assume one combination of histone modification invariantly translates to one transcriptional output regardless of local chromatin environment. In this study we hypothesize that, the genome is organized into local domains that manifest similar enrichment pattern of histone modification, which leads to orchestrated regulation of expression of genes with relevant biological functions. We propose a multivariate Bayesian Change Point (BCP) model to segment the Drosophila melanogaster genome into consecutive blocks on the basis of combinatorial patterns of histone marks. By modeling the sparse distribution of histone marks with a zero-inflated Gaussian mixture, our partitions capture local BLOCKs that manifest relatively homogeneous enrichment pattern of histone marks. We further characterized BLOCKs by their transcription levels, distribution of genes, degree of co-regulation and GO enrichment. Our results demonstrate that these BLOCKs, although inferred merely from histone modifications, reveal strong relevance with physical domains, which suggests their important roles in chromatin organization and coordinated gene regulation

Deciphering the role of RNA structure in translation efficiency.

BACKGROUND: RNA secondary structure has broad impact on the fate of RNA metabolism. The reduced stability of secondary structures near the translation initiation site/start codon of the coding region promotes the efficiency of translation in both prokaryotic and eukaryotic species. However, the inaccuracy of in silico folding and the focus on the coding region limit our understanding of the global relationship between the whole mRNA structure and translation efficiency. Leveraging high-throughput RNA structure probing data in the transcriptome, we aim to systematically investigate the role of RNA structure in regulating translation efficiency. RESULTS: Here, we analyze the influences of hundreds of sequence and structural features on translation efficiency in the mouse embryonic stem cells (mESCs) and zebrafish developmental stages. Our findings reveal that overall in vivo RNA structure has a higher relative importance in predicting translation efficiency than in vitro RNA structure in both mESCs and zebrafish. Also, RNA structures in 3\u27 untranslated region (UTR) have much stronger influence on translation efficiency compared to those in coding regions or 5\u27 UTR. Furthermore, strong alternation between in vitro and in vivo structures in 3\u27 UTR are detected in highly translated mRNAs in mESCs but not zebrafish. Instead, moderate alteration between in vitro and in vivo RNA structures in the 5\u27 UTR and proximal coding regions are detected in highly translated mRNAs in zebrafish. CONCLUSIONS: Our results suggest the openness of the 3\u27 UTR promotes the translation efficiency in both mice and zebrafish, with the in vivo structure in 3\u27 UTR more important in mice than in zebrafish. This reveals a novel role of RNA secondary structure on translational regulation

PIWI proteins are essential for early Drosophila embryogenesis

AbstractPIWI proteins, a subfamily of the ARGONAUTE/PIWI protein family, have been implicated in transcriptional and posttranscriptional gene regulation and transposon silencing mediated by small non-coding RNAs, especially piRNAs. Although these proteins are known to be required for germline development, their somatic function remains elusive. Here, we examine the maternal function of all three PIWI proteins in Drosophila; Piwi, Aubergine (Aub) and Argonaute3 (Ago3) during early embryogenesis. In syncytial embryos, Piwi displays an embryonic stage-dependent localization pattern. Piwi is localized in the cytoplasm during mitotic cycles 1–10. Between cycles 11 and 14, Piwi remains in the cytoplasm during mitosis but moves into the somatic nucleus during interphase. Beyond cycle 14, it stays in the nucleus. Aub and Ago3 are diffusely cytoplasmic from cycle 1 to 14. Embryos maternally depleted of any one of the three PIWI proteins display severe mitotic defects, including abnormal chromosome and nuclear morphology, cell cycle arrest, asynchronous nuclear division and aberrant nuclear migration. Furthermore, all three PIWI proteins are required for the assembly of mitotic machinery and progression through mitosis. Embryos depleted of maternal PIWI proteins also exhibit chromatin organization abnormalities. These observations indicate that maternal Piwi, Aub and Ago3 play a critical role in the maintenance of chromatin structure and cell cycle progression during early embryogenesis, with compromised chromatin integrity as a possible cause of the observed mitotic defects. Our study demonstrates the essential function of PIWI proteins in the first phase of somatic development

RIS-Aided Wireless Communications: Prototyping, Adaptive Beamforming, and Indoor/Outdoor Field Trials

The prospects of using a Reconfigurable Intelligent Surface (RIS) to aid wireless communication systems have recently received much attention from academia and industry. Most papers make theoretical studies based on elementary models, while the prototyping of RIS-aided wireless communication and real-world field trials are scarce. In this paper, we describe a new RIS prototype consisting of 1100 controllable elements working at 5.8 GHz band. We propose an efficient algorithm for configuring the RIS over the air by exploiting the geometrical array properties and a practical receiver-RIS feedback link. In our indoor test, where the transmitter and receiver are separated by a 30 cm thick concrete wall, our RIS prototype provides a 26 dB power gain compared to the baseline case where the RIS is replaced by a copper plate. A 27 dB power gain was observed in the short-distance outdoor measurement. We also carried out long-distance measurements and successfully transmitted a 32 Mbps data stream over 500 m. A 1080p video was live-streamed and it only played smoothly when the RIS was utilized. The power consumption of the RIS is around 1 W. Our paper is vivid proof that the RIS is a very promising technology for future wireless communications.Comment: 13 pages, 18 figures, submitte

Reassessment of Piwi Binding to the Genome and Piwi Impact on RNA Polymerase II Distribution

Drosophila Piwi was reported by Huang et al. (2013) to be guided by piRNAs to piRNA-complementary sites in the genome, which then recruits Heterochromatin Protein 1a and histone methyltransferase Su(Var)3-9 to the sites. Among additional findings, Huang et al. (2013) also reported Piwi binding sites in the genome and the reduction of RNA polymerase II in euchromatin but its increase in pericentric regions in piwi mutants. Marinov et al. (2015) disputed the validity of the Huang et al. bioinformatic pipeline that led to the last two claims. Here we report our independent reanalysis of the data using current bioinformatic methods. Our reanalysis agrees with Marinov et al. (2015) that Piwi’s genomic targets still remain to be identified, yet confirms the Huang et al. claim that Piwi influences RNA polymerase II distribution in the genome. This Response addresses the Marinov et al. (2015) Matters Arising, published concurrently in Developmental Cell

Enhancing LTE with Cloud-RAN and Load-Controlled Parasitic Antenna Arrays

Cloud radio access network systems, consisting of remote radio heads densely distributed in a coverage area and connected by optical fibers to a cloud infrastructure with large computational capabilities, have the potential to meet the ambitious objectives of next generation mobile networks. Actual implementations of C-RANs tackle fundamental technical and economic challenges. In this article, we present an end-to-end solution for practically implementable C-RANs by providing innovative solutions to key issues such as the design of cost-effective hardware and power-effective signals for RRHs, efficient design and distribution of data and control traffic for coordinated communications, and conception of a flexible and elastic architecture supporting dynamic allocation of both the densely distributed RRHs and the centralized processing resources in the cloud to create virtual base stations. More specifically, we propose a novel antenna array architecture called load-controlled parasitic antenna array (LCPAA) where multiple antennas are fed by a single RF chain. Energy- and spectral-efficient modulation as well as signaling schemes that are easy to implement are also provided. Additionally, the design presented for the fronthaul enables flexibility and elasticity in resource allocation to support BS virtualization. A layered design of information control for the proposed end-to-end solution is presented. The feasibility and effectiveness of such an LCPAA-enabled C-RAN system setup has been validated through an over-the-air demonstration

A High-Resolution Whole-Genome Map of Key Chromatin Modifications in the Adult Drosophila melanogaster

Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP–Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications