Life Sciences Commons^™

Path-Seq Identifies An Essential Mycolate Remodeling Program For Mycobacterial Host Adaptation., Eliza Jr Peterson, Rebeca Bailo, Alissa C Rothchild, Mario L Arrieta-Ortiz, Amardeep Kaur, Min Pan, Dat Mai, Abrar A Abidi, Charlotte Cooper, Alan Aderem, Apoorva Bhatt, Nitin S Baliga

Articles, Abstracts, and Reports

The success of Mycobacterium tuberculosis (MTB) stems from its ability to remain hidden from the immune system within macrophages. Here, we report a new technology (Path-seq) to sequence miniscule amounts of MTB transcripts within up to million-fold excess host RNA Using Path-seq and regulatory network analyses, we have discovered a novel transcriptional program for in vivo mycobacterial cell wall remodeling when the pathogen infects alveolar macrophages in mice. We have discovered that MadR transcriptionally modulates two mycolic acid desaturases desA1/desA2 to initially promote cell wall remodeling upon in vitro macrophage infection and, subsequently, reduces mycolate biosynthesis upon entering …

Optram: In-Silico Strain Design Via Integrative Regulatory-Metabolic Network Modeling., Fangzhou Shen, Renliang Sun, Jie Yao, Jian Li, Qian Liu, Nathan D Price, Chenguang Liu, Zhuo Wang

Articles, Abstracts, and Reports

The ultimate goal of metabolic engineering is to produce desired compounds on an industrial scale in a cost effective manner. To address challenges in metabolic engineering, computational strain optimization algorithms based on genome-scale metabolic models have increasingly been used to aid in overproducing products of interest. However, most of these strain optimization algorithms utilize a metabolic network alone, with few approaches providing strategies that also include transcriptional regulation. Moreover previous integrated approaches generally require a pre-existing regulatory network. In this study, we developed a novel strain design algorithm, named OptRAM (Optimization of Regulatory And Metabolic Networks), which can identify combinatorial …

A Tandem Mass Spectrometry Sequence Database Search Method For Identification Of O-Fucosylated Proteins By Mass Spectrometry., Kristian E Swearingen, Jimmy K Eng, David Shteynberg, Vladimir Vigdorovich, Timothy A Springer, Luis Mendoza, D Noah Sather, Eric W Deutsch, Stefan H I Kappe, Robert L Moritz

Articles, Abstracts, and Reports

Thrombospondin type 1 repeats (TSRs), small adhesive protein domains with a wide range of functions, are usually modified with O-linked fucose, which may be extended to O-fucose-β1,3-glucose. Collision-induced dissociation (CID) spectra of O-fucosylated peptides cannot be sequenced by standard tandem mass spectrometry (MS/MS) sequence database search engines because O-linked glycans are highly labile in the gas phase and are effectively absent from the CID peptide fragment spectra, resulting in a large mass error. Electron transfer dissociation (ETD) preserves O-linked glycans on peptide fragments, but only a subset of tryptic peptides with low m/ z can be reliably sequenced from ETD …

Mitf Has A Central Role In Regulating Starvation-Induced Autophagy In Melanoma., Katrin Möller, Sara Sigurbjornsdottir, Asgeir O Arnthorsson, Vivian Pogenberg, Ramile Dilshat, Valerie Fock, Solveig H Brynjolfsdottir, Christian Bindesboll, Margret Bessadottir, Helga M Ogmundsdottir, Anne Simonsen, Lionel Larue, Matthias Wilmanns, Vesteinn Thorsson, Eirikur Steingrimsson, Margret H Ogmundsdottir

Articles, Abstracts, and Reports

The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. The crystal structure of MITF bound to the CLEAR-box reveals how the palindromic nature of this motif induces symmetric MITF homodimer binding. In metastatic melanoma tumors and cell lines, MITF positively correlates with the expression of lysosomal and autophagosomal genes, which, interestingly, …

Gene Annotation Errors Are Common In The Mammalian Mitochondrial Genomes Database., Carlos F Prada, Jeffrey L Boore

Articles, Abstracts, and Reports

BACKGROUND: Although animal mitochondrial DNA sequences are known to evolve rapidly, their gene arrangements often remain unchanged over long periods of evolutionary time. Therefore, comparisons of mitochondrial genomes may result in significant insights into the evolution both of organisms and of genomes. Mammalian mitochondrial genomes recently published in the GenBank database of NCBI show numerous rearrangements in various regions of the genome, from which it may be inferred that the mammalian mitochondrial genome is more dynamic than expected. However, it is alternatively possible that these are errors of annotation and, if so, are misleading our interpretations. In order to verify …

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis., Sean J O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A S Reyes, Jon Gorky, Rajanikanth Vadigepalli, Elisabeth J Van Bockstaele, James S Schwaber

Articles, Abstracts, and Reports

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably

Proximate Grassland And Shrub-Encroached Sites Show Dramatic Restructuring Of Soil Bacterial Communities., Xingjia Xiang, Sean M Gibbons, He Li, Haihua Shen, Haiyan Chu

Articles, Abstracts, and Reports

Background: Changes in aboveground community composition and diversity following shrub encroachment have been studied extensively. Recently, shrub encroachment was associated with differences in belowground bacterial communities relative to non-encroached grassland sites hundreds of meters away. This spatial distance between grassland and shrub sites left open the question of how soil bacterial communities associated with different vegetation types might differ within the same plot location.

Methods: We examined soil bacterial communities between shrub-encroached and adjacent (one m apart) grassland soils in Chinese Inner Mongolian, using high-throughput sequencing method (Illumina, San Diego, CA, USA).

Results: Shrub-encroached sites were associated with dramatic restructuring …

Adapts: Automated Deconvolution Augmentation Of Profiles For Tissue Specific Cells., Samuel A Danziger, David L Gibbs, Ilya Shmulevich, Mark Mcconnell, Matthew W B Trotter, Frank Schmitz, David J Reiss, Alexander V Ratushny

Articles, Abstracts, and Reports

Immune cell infiltration of tumors and the tumor microenvironment can be an important component for determining patient outcomes. For example, immune and stromal cell presence inferred by deconvolving patient gene expression data may help identify high risk patients or suggest a course of treatment. One particularly powerful family of deconvolution techniques uses signature matrices of genes that uniquely identify each cell type as determined from single cell type purified gene expression data. Many methods from this family have been recently published, often including new signature matrices appropriate for a single purpose, such as investigating a specific type of tumor. The …

Reproducible Big Data Science: A Case Study In Continuous Fairness., Ravi Madduri, Kyle Chard, Mike D'Arcy, Segun C Jung, Alexis Rodriguez, Dinanath Sulakhe, Eric W Deutsch, Cory C Funk, Ben Heavner, Matthew A Richards, Paul Shannon, Gustavo Glusman, Nathan D Price, Carl Kesselman, Ian Foster

Articles, Abstracts, and Reports

Big biomedical data create exciting opportunities for discovery, but make it difficult to capture analyses and outputs in forms that are findable, accessible, interoperable, and reusable (FAIR). In response, we describe tools that make it easy to capture, and assign identifiers to, data and code throughout the data lifecycle. We illustrate the use of these tools via a case study involving a multi-step analysis that creates an atlas of putative transcription factor binding sites from terabytes of ENCODE DNase I hypersensitive sites sequencing data. We show how the tools automate routine but complex tasks, capture analysis algorithms in understandable and …

Lymphatic Migration Of Immune Cells., Henry R Hampton, Tatyana Chtanova

Articles, Abstracts, and Reports

Lymphatic vessels collect interstitial fluid that has extravasated from blood vessels and return it to the circulatory system. Another important function of the lymphatic network is to facilitate immune cell migration and antigen transport from the periphery to draining lymph nodes. This migration plays a crucial role in immune surveillance, initiation of immune responses and tolerance. Here we discuss the significance and mechanisms of lymphatic migration of innate and adaptive immune cells in homeostasis, inflammation and cancer.

Fe Limitation Decreases Transcriptional Regulation Over The Diel Cycle In The Model Diatom Thalassiosira Pseudonana., Johanna A L Goldman, Megan J Schatz, Chris T Berthiaume, Sacha N Coesel, Mónica V Orellana, E Virginia Armbrust

Articles, Abstracts, and Reports

Iron (Fe) is an important growth factor for diatoms and its availability is further restricted by changes in the carbonate chemistry of seawater. We investigated the physiological attributes and transcriptional profiles of the diatom Thalassiosira pseudonana grown on a day: night cycle under different CO2/pH and iron concentrations, that in combination generated available iron (Fe') concentrations of 1160, 233, 58 and 12 pM. We found the light-dark conditions to be the main driver of transcriptional patterns, followed by Fe' concentration and CO2 availability, respectively. At the highest Fe' (1160 pM), 55% of the transcribed genes were differentially expressed between day …