SubpathwayMiner: a software package for flexible identification of pathways

With the development of high-throughput experimental techniques such as microarray, mass spectrometry and large-scale mutagenesis, there is an increasing need to automatically annotate gene sets and identify the involved pathways. Although many pathway analysis tools are developed, new tools are still needed to meet the requirements for flexible or advanced analysis purpose. Here, we developed an R-based software package (SubpathwayMiner) for flexible pathway identification. SubpathwayMiner facilitates subpathway identification of metabolic pathways by using pathway structure information. Additionally, SubpathwayMiner also provides more flexibility in annotating gene sets and identifying the involved pathways (entire pathways and sub-pathways): (i) SubpathwayMiner is able to provide the most up to- date pathway analysis results for users; (ii) SubpathwayMiner supports multiple species (~100 eukaryotes, 714 bacteria and 52 Archaea) and different gene identifiers (Entrez Gene IDs, NCBI-gi IDs, UniProt IDs, PDB IDs, etc.) in the KEGG GENE database; (iii) the system is quite efficient in cooperating with other R-based tools in biology. SubpathwayMiner is freely available at http://cran.r-project.org/web/packages/SubpathwayMiner/

The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of mitophagy

Mitophagy is a critical process that safeguards mitochondrial quality control in order to maintain proper cellular homeostasis. Although the mitochondrial-anchored receptor Atg32-mediated cargo-recognition system has been well characterized to be essential for this process, the signaling pathway modulating its expression as a contribution of governing the mitophagy process remains largely unknown. Here, bioinformatics analyses of epigenetic or transcriptional regulators modulating gene expression allow us to identify the Paf1 complex (the polymerase-associated factor 1 complex, Paf1C,) as a transcriptional repressor of ATG genes. We show that Paf1C suppresses glucose starvation-induced autophagy, but does not affect nitrogen starvation- or rapamycin-induced autophagy. Moreover, we show that Paf1C specifically regulates mitophagy through modulating ATG32 expression. Deletion of the genes encoding two core subunits of Paf1C, Paf1 and Ctr9, increases ATG32 and ATG11 expression and facilitates mitophagy activity. Although Paf1C is required for many histone modifications and gene activation, we show that Paf1C regulates mitophagy independent of its positive regulatory role in other processes. More importantly, we also demonstrate the mitophagic role of PAF1C in mammals. Overall, we conclude that Paf1C maintains mitophagy at a low level through binding the promoter of the ATG32 gene in glucose-rich conditions. Dissociation of Paf1C from ATG32 leads to the increased expression of this gene, and mitophagy induction upon glucose starvation. Thus, we uncover a new role of Paf1C in modulating the mitophagy process at the transcriptional level

Airflow Dynamics of Human Jets: Sneezing and Breathing - Potential Sources of Infectious Aerosols

10.1371/journal.pone.0059970PLoS ONE84

In-depth mining of single-cell transcriptome reveals the key immune-regulated loops in age-related macular degeneration

IntroductionAge-related macular degeneration (AMD), an ever-increasing ocular disease, has become one of the leading causes of irreversible blindness. Recent advances in single-cell genomics are improving our understanding of the molecular mechanisms of AMD. However, the pathophysiology of this multifactorial disease is complicated and still an ongoing challenge. To better understand disease pathogenesis and identify effective targets, we conducted an in-depth analysis of the single-cell transcriptome of AMD.MethodsThe cell expression specificity of the gene (CESG) was selected as an index to identify the novel cell markers. A computational framework was designed to explore the cell-specific TF regulatory loops, containing the interaction of gene pattern signatures, transcription factors regulons, and differentially expressed genes.ResultsThree potential novel cell markers were DNASE1L3 for endothelial cells, ABCB5 for melanocytes, and SLC39A12 for RPE cells detected. We observed a notable change in the cell abundance and crosstalk of fibroblasts cells, melanocytes, schwann cells, and T/NK cells between AMD and controls, representing a complex cellular ecosystem in disease status. Finally, we identified six cell type related and three disease-associated ternary loops and elaborated on the robust association between key immune-pathway and AMD.DiscussionIn conclusion, this study facilitates the optimization of screening for AMD-related receptor ligand pathways and proposes to further improve the interpretability of disease associations from single-cell data. It illuminated that immune-related regulation paths could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, providing insights into AMD diagnosis and potential interventions

Mid-Infrared Continuous Varifocal Metalens with Adjustable Intensity Based on Phase Change Materials

Metalenses can greatly reduce the complexity of imaging systems due to their small size and light weight and also provide a platform for the realization of multifunctional imaging devices. Achieving dynamic focus length tunability is highly important for metalens research. In this paper, based on single-crystal Ge and a new low-loss phase change material Ge2Sb2Se5 (GSSe), a tunable metalens formed by a double-layer metasurface composite was realized in the mid-infrared band. The first-layer metasurface formed by Ge nanopillars combines propagation and the geometric phase (equivalent to a half-wave plate function) to produce single- or multiple-polarization-dependent foci. The second-layer metasurface formed by GSSe nanopillars provides a tunable propagation phase, and the double-layer metalens can achieve the tunability of the focus length depending on the different crystalline fractions of GSSe. The focal length varies from 62.91 to 67.13 μm under right circularly polarized light incidence and from 33.84 to 36.66 μm under left circularly polarized light incidence. Despite the difference in the crystallographic fraction, the metalens’s focusing efficiency is maintained basically around 59% and 48% when zooming under RCP and LCP wave excitation. Meanwhile, the incident wave’s ellipticity can be changed to alter the relative intensity ratios of the bifocals from 0.03 to 4.26. This continuous varifocal metalens with adjustable intensity may have potential in practical applications such as optical tomography, multiple imaging, and systems of optical communication

LncRNA Structural Characteristics in Epigenetic Regulation

The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes

Neuropathic Pain: Epidemiology, Classification, Mechanisms, and Therapy

Neuropathic pain develops because of lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Examples of neuropathic pain include painful polyneuropathy, post herpetic neuralgia, trigeminal neuralgia, and post-stroke pain. Clinically, neuropathic pain is characterized by spontaneous ongoing or shooting pain and evoked amplified pain responses after noxious or non-noxious stimuli. Methods such as questionnaires for screening and assessment focus on the presence and quality of neuropathic pain. Basic research is enabling the identification of different pathophysiological mechanisms, and clinical assessment of symptoms and signs can help to determine which mechanisms are involved in specific neuropathic pain disorders. Management of neuropathic pain requires an interdisciplinary approach, centered on pharmacological treatment. A better understanding of neuropathic pain and, in particular, of the translation of pathophysiological mechanisms into sensory signs will lead to a more effective and specific mechanism-based treatment approach

RNAsmc: A integrated tool for comparing RNA secondary structure and evaluating allosteric effects

RNA structure plays a crucial role in gene regulation, in RNA stability and the essential biological processes. RNA secondary structure (RSS) motifs are the basic building blocks for investigating the biological mechanisms of structure. Here, we present a strategy for structural motif-based dynamic alignment, namely, RNA secondary-structural motif-comparing (RNAsmc), to identify structural motifs and quantitatively evaluate their underlying molecular functions. RNAsmc also has strong robustness to sequence length, folding protocol and RNA structural profile by chemical probing. Notably, it is also applicable to quantify structural variation in special RNA editing events (SNVs or SNPs, fragment insertion or deletion, etc.). The findings indicate that RNAsmc can uncover the heterogeneity of RNA secondary structure and score for similarities among components, which provides an impetus to cluster RNA families and evaluate allosteric effects. We find that RNAsmc exhibits remarkable detection efficiency for experimentally-derived RiboSNitches. Finally, the pipeline was assembled into an R software package to serve as an automated toolkit to explore, align, and cluster RSS. It is freely available for download at https://CRAN.R-project.org/package=RNAsmc