Ig Superfamily Ligand and Receptor Pairs Expressed in Synaptic Partners in Drosophila

Information processing relies on precise patterns of synapses between neurons. The cellular recognition mechanisms regulating this specificity are poorly understood. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Here, we sought to identify candidate cell recognition molecules underlying this specificity. Using RNA sequencing (RNA-seq), we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA-seq and protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig-containing proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity

The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs

Pandora, a PAthway and Network DiscOveRy Approach based on common biological evidence

Motivation: Many biological phenomena involve extensive interactions between many of the biological pathways present in cells. However, extraction of all the inherent biological pathways remains a major challenge in systems biology. With the advent of high-throughput functional genomic techniques, it is now possible to infer biological pathways and pathway organization in a systematic way by integrating disparate biological information

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

CAERUS: predicting CAncER oUtcomeS using relationship between protein structural information, protein networks, gene expression data, and mutation data.

Carcinogenesis is a complex process with multiple genetic and environmental factors contributing to the development of one or more tumors. Understanding the underlying mechanism of this process and identifying related markers to assess the outcome of this process would lead to more directed treatment and thus significantly reduce the mortality rate of cancers. Recently, molecular diagnostics and prognostics based on the identification of patterns within gene expression profiles in the context of protein interaction networks were reported. However, the predictive performances of these approaches were limited. In this study we propose a novel integrated approach, named CAERUS, for the identification of gene signatures to predict cancer outcomes based on the domain interaction network in human proteome. We first developed a model to score each protein by quantifying the domain connections to its interacting partners and the somatic mutations present in the domain. We then defined proteins as gene signatures if their scores were above a preset threshold. Next, for each gene signature, we quantified the correlation of the expression levels between this gene signature and its neighboring proteins. The results of the quantification in each patient were then used to predict cancer outcome by a modified naïve Bayes classifier. In this study we achieved a favorable accuracy of 88.3%, sensitivity of 87.2%, and specificity of 88.9% on a set of well-documented gene expression profiles of 253 consecutive breast cancer patients with different outcomes. We also compiled a list of cancer-associated gene signatures and domains, which provided testable hypotheses for further experimental investigation. Our approach proved successful on different independent breast cancer data sets as well as an ovarian cancer data set. This study constitutes the first predictive method to classify cancer outcomes based on the relationship between the domain organization and protein network

Rapid Changes in the Translatome during the Conversion of Growth Cones to Synaptic Terminals

Summary: A common step in the formation of neural circuits is the conversion of growth cones to presynaptic terminals. Characterizing patterns of global gene expression during this process is problematic due to the cellular diversity of the brain and the complex temporal dynamics of development. Here, we take advantage of the synchronous conversion of Drosophila photoreceptor growth cones into presynaptic terminals to explore global changes in gene expression during presynaptic differentiation. Using a tandemly tagged ribosome trap (T-TRAP) and RNA sequencing (RNA-seq) at multiple developmental times, we observed dramatic changes in coding and non-coding RNAs with presynaptic differentiation. Marked changes in the mRNA encoding transmembrane and secreted proteins occurred preferentially. The 3′ UTRs of transcripts encoding synaptic proteins were preferentially lengthened, and these extended UTRs were preferentially enriched for sites recognized by RNA binding proteins. These data provide a rich resource for uncovering the regulatory logic underlying presynaptic differentiation. : Using a tandemly tagged ribosome trap (T-TRAP) and RNA sequencing (RNA-seq), Zhang et al. take advantage of the synchronous conversion of Drosophila photoreceptor growth cones into presynaptic terminals to explore global changes in gene expression associated with this step in neuronal differentiation

Tuning the electronic structure of NiO via Li doping for the fast oxygen evolution reaction

Transition metal oxides are being actively pursued as low-cost electrocatalysts for the oxygen evolution reaction (OER) in many electrochemical energy devices. A fundamental understanding of the oxide electronic structures, along with the ability to rationally tune them, is a key step toward designing of highly active catalysts. Here, we report the tuning of the electronic structure of NiO via Li doping (LixNi1–xO) to enhance the OER activities. We identified that Li0.5Ni0.5O (LiNiO2) has the highest OER activity, comparable to or exceeding that of the benchmark perovskite Ba0.5Sr0.5Co0.8Fe0.2O3−δ and LaNiO3. More importantly, a synergistic combination of synchrotron-based photoemission spectroscopy, X-ray absorption spectroscopy, and density functional theory was used to unravel the electronic structure of LixNi1–xO with unprecedented accuracy, thus providing deep insight into the origin of the enhanced catalytic activity. The results unambiguously reveal the creation of a new hole state at 1.1 eV above the Fermi level and an enhanced degree of O 2p–Ni 3d hybridization induced by Li doping optimize the adsorption energetics of OH intermediates and thereby facilitate the fast kinetics for the OER. The LixNi1–xO would serve as a new platform to study the relationship of composition–electronic structure–activity for OER electrocatalysts, beyond the extensively studied Co-based perovskites

Facilitating the Deprotonation of OH to O through Fe⁴⁺ -Induced States in Perovskite LaNiO₃ Enables a Fast Oxygen Evolution Reaction.

Aliovalent doping has been widely adopted to tune the electronic structure of transition-metal oxides for design of low-cost, active electrocatalysts. Here, using single-crystalline thin films as model electrocatalysts, we study the structure-activity relationship of Fe states doping in perovskite LaNiO3 for oxygen evolution reaction (OER). We found Fe4+ state is crucial for enhancing the OER activity of LaNiO3, dramatically increasing the activity by 6 times, while Fe3+ has negligible effect. Spectroscopic studies and DFT calculations indicate Fe4+ states enhance the degree of Ni/Fe 3d and O 2p hybridization, and meanwhile produces down-shift of the unoccupied density of states towards lower energies. Such electronic features reduce the energy barrier for interfacial electron transfer for water oxidization by 0.2 eV. Further theoretical calculations and H/D isotope experiments reveal the electronic states associated with Fe4+-O2--Ni3+ configuration accelerates the deprotonation of *OH to *O (rate-determining step), and thus facilitates fast OER kinetics.Royal Academy of Engineering - CIET1819_24, Leverhulme Trust grant RPG-2015-017, EPSRC grants EP/N004272/1, EP/T012218/1, EP/P007767/1, and EP/M000524