Macro-physical, optical and radiative properties of tropical cirrus clouds and its temperature dependence at Gadanki (13.5° N, 79.2° E) observed by ground based lidar

The macro-physical and optical properties of cirrus clouds and its temperature dependencies have been investigated at the National Atmospheric Research Laboratory (NARL; 13.5° N, 79.2° E), Gadanki, Andhra Pradesh, India; an inland tropical station during the period of observation January to December 2009 using a ground based pulsed monostatic lidar system data and radiosonde measurements. Based on the analysis of measurements the cirrus macrophysical properties such as occurrence height, mid cloud temperature, cloud geometrical thickness, and optical properties such as extinction coefficient, optical depth, depolarization ratio and lidar ratio have been determined. The variation of cirrus macrophysical and optical properties with mid cloud temperature have also been studied. The cirrus clouds mean height has been generally observed in the range of 9-17 km with a peak occurrence at 13-14 km. The cirrus mid cloud temperatures were in the range from -81 °C to -46 °C. The cirrus geometrical thickness ranges from 0.9-4.5 km and 56% of cirrus occurrences have thickness 1.0 -2.7 km. The monthly cirrus optical depth ranges from 0.01-0.47, but most (>80%) of the cirrus have values less than 0.1. The monthly mean cirrus extinction ranges from 2.8E-06 to 8E-05 and depolarization ratio and lidar ratio varies from 0.13 to 0.77 and 2 to 52 respectively. The temperature and thickness dependencies on cirrus optical properties have also been studied. A maximum cirrus geometrical thickness of 4.5 km is found at temperatures around – 46 °C with an indication that optical depth increases with increasing thickness and mid cloud temperature. The cloud radiative properties such as outgoing long-wave radiation (OLR) flux and cirrus IR forcing are studied. OLR flux during the cirrus occurrence days ranged from 348-456 W/m2 with a low value in the monsoon period. The cirrus IR forcing varied from 3.13 – 110.54 W/m2 and shows a peak at monsoon period

ENCODE whole-genome data in the UCSC genome browser (2011 update)

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access

Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Abstract Background Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. Results To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. Discussion Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. Conclusions Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment.https://deepblue.lib.umich.edu/bitstream/2027.42/142394/1/12864_2018_Article_4533.pd

Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Abstract Background Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. Results To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. Discussion Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. Conclusions Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment

Open collaborative writing with Manubot.

Open, collaborative research is a powerful paradigm that can immensely strengthen the scientific process by integrating broad and diverse expertise. However, traditional research and multi-author writing processes break down at scale. We present new software named Manubot, available at https://manubot.org, to address the challenges of open scholarly writing. Manubot adopts the contribution workflow used by many large-scale open source software projects to enable collaborative authoring of scholarly manuscripts. With Manubot, manuscripts are written in Markdown and stored in a Git repository to precisely track changes over time. By hosting manuscript repositories publicly, such as on GitHub, multiple authors can simultaneously propose and review changes. A cloud service automatically evaluates proposed changes to catch errors. Publication with Manubot is continuous: When a manuscript's source changes, the rendered outputs are rebuilt and republished to a web page. Manubot automates bibliographic tasks by implementing citation by identifier, where users cite persistent identifiers (e.g. DOIs, PubMed IDs, ISBNs, URLs), whose metadata is then retrieved and converted to a user-specified style. Manubot modernizes publishing to align with the ideals of open science by making it transparent, reproducible, immediate, versioned, collaborative, and free of charge

Transcription pausing regulates mouse embryonic stem cell differentiation

The pluripotency of embryonic stem cells (ESCs) relies on appropriate responsiveness to developmental cues. Promoter-proximal pausing of RNA polymerase II (Pol II) has been suggested to play a role in keeping genes poised for future activation. To identify the role of Pol II pausing in regulating ESC pluripotency, we have generated mouse ESCs carrying a mutation in the pause-inducing factor SPT5. Genomic studies reveal genome-wide reduction of paused Pol II caused by mutant SPT5 and further identify a tight correlation between pausing-mediated transcription effect and local chromatin environment. Functionally, this pausing-deficient SPT5 disrupts ESC differentiation upon removal of self-renewal signals. Thus, our study uncovers an important role of Pol II pausing in regulating ESC differentiation and suggests a model that Pol II pausing coordinates with epigenetic modification to influence transcription during mESC differentiation

Lidar investigations on the optical and dynamical properties of cirrus clouds in the upper troposphere and lower stratosphere regions at a tropical station, Gadanki, India (13.5 degrees N, 79.2 degrees E)

High altitude cirrus clouds are composed mainly of ice crystals with a variety of sizes and shapes. They have a large influence on Earth's energy balance and global climate. Recent studies indicate that the formation, dissipation, life time, optical, and micro-physical properties are influenced by the dynamical conditions of the surrounding atmosphere like background aerosol, turbulence, etc. In this work, an attempt has been made to quantify some of these characteristics by using lidar and mesosphere-stratosphere-troposphere (MST) radar. Mie lidar and 53 MHz MST radar measurements made over 41 nights during the period 2009 to 2010 from the tropical station, Gadanki, India (13.5 degrees N, 79.2 degrees E). The optical and microphysical properties along with the structure and dynamics of the cirrus are presented as observed under different atmospheric conditions. The study reveals the manifestation of different forms of cirrus with a preferred altitude of formation in the 13 to 14 km altitude. There are considerable differences in the properties obtained among 2009 and 2010 showing significant anomalous behavior in 2010. The clouds observed during 2010 show relatively high asymmetry and large multiple scattering effects. The anomalies found during 2010 may be attributed to the turbulence noticed in the surrounding atmosphere. The results show a clear correlation between the crystal morphology in the clouds and the dynamical conditions of the prevailing atmosphere during the observational period. (c) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE

Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers.

The cardiogenic transcription factors (TFs) Mef2c, Gata4, and Tbx5 can directly reprogram fibroblasts to induced cardiac-like myocytes (iCLMs), presenting a potential source of cells for cardiac repair. While activity of these TFs is enhanced by Hand2 and Akt1, their genomic targets and interactions during reprogramming are not well studied. We performed genome-wide analyses of cardiogenic TF binding and enhancer profiling during cardiac reprogramming. We found that these TFs synergistically activate enhancers highlighted by Mef2c binding sites and that Hand2 and Akt1 coordinately recruit other TFs to enhancer elements. Intriguingly, these enhancer landscapes collectively resemble patterns of enhancer activation during embryonic cardiogenesis. We further constructed a cardiac reprogramming gene regulatory network and found repression of EGFR signaling pathway genes. Consistently, chemical inhibition of EGFR signaling augmented reprogramming. Thus, by defining epigenetic landscapes these findings reveal synergistic transcriptional activation across a broad landscape of cardiac enhancers and key signaling pathways that govern iCLM reprogramming

Suppression of Myeloid Cell Arginase Activity leads to Therapeutic Response in a NSCLC Mouse Model by Activating Anti-Tumor Immunity

Abstract Background Tumor orchestrated metabolic changes in the microenvironment limit generation of anti-tumor immune responses. Availability of arginine, a semi-essential amino acid, is critical for lymphocyte proliferation and function. Levels of arginine are regulated by the enzymes arginase 1,2 and nitric oxide synthase (NOS). However, the role of arginase activity in lung tumor maintenance has not been investigated in clinically relevant orthotopic tumor models. Methods RNA sequencing (RNA-seq) of sorted cell populations from mouse lung adenocarcinomas derived from immunocompetent genetically engineered mouse models (GEMM)s was performed. To complement mouse studies, a patient tissue microarray consisting of 150 lung adenocarcinomas, 103 squamous tumors, and 54 matched normal tissue were stained for arginase, CD3, and CD66b by multiplex immunohistochemistry. Efficacy of a novel arginase inhibitor compound 9 in reversing arginase mediated T cell suppression was determined in splenocyte ex vivo assays. Additionally, the anti-tumor activity of this compound was determined in vitro and in an autochthonous immunocompetent KrasG12D GEMM of lung adenocarcinoma model. Results Analysis of RNA-seq of sorted myeloid cells suggested that arginase expression is elevated in myeloid cells in the tumor as compared to the normal lung tissue. Accordingly, in the patient samples arginase 1 expression was mainly localized in the granulocytic myeloid cells and significantly elevated in both lung adenocarcinoma and squamous tumors as compared to the controls. Our ex vivo analysis demonstrated that myeloid derived suppressor cell (MDSC)s cause T cell suppression by arginine depletion, and suppression of arginase activity by a novel ARG1/2 inhibitor, compound 9, led to restoration of T cell function by increasing arginine. Treatment of KrasG12D GEMM of lung cancer model with compound 9 led to a significant tumor regression associated with increased T cell numbers and function, while it had no activity across several murine and human non-small cell (NSCLC) lung cancer lines in vitro. Conclusions We show that arginase expression is elevated in mouse and patient lung tumors. In a KRASG12D GEMM arginase inhibition diminished growth of established tumors. Our data suggest arginase as an immunomodulatory target that should further be investigated in lung tumors with high arginase activity