news

Viewing posts from the news category

High CO2 Associated with Downregulation of Skeletal Muscle Synthesis and Ribosomal Biogenesis

High levels of CO2 downregulates skeletal muscle protein anabolism, according to a recent paper by TC Korponay et al (2020)  in the American Journal of American Journal of Respiratory Cell and Molecular Biology.

Two independent conditions are associated with worse outcomes in patients with chronic pulmonary diseases; the retention of a high amount of Co2 (also called “hypercapnia”) and skeletal muscle wasting (also associated with worse outcomes in acute pulmonary disease).
Due to the current lack of research on the role of high CO2 levels in regulating skeletal muscle anabolism, researchers sought to investigate the role of high CO2 levels in weakening skeletal muscle protein synthesis in both patients and mice.

Researchers found that locomotor muscles from patients with chronic CO2 retention had decreased ribosomal gene expression in comparison to patients who did not retain CO2 to the same extent. Additionally, researchers found that mice in a high-CO2 environment had downregulated ribosomal biogenesis in their skeletal muscles, as well as decreased protein synthesis.

Evidently, researchers found that there was an impact of high CO2 levels on skeletal muscle synthesis and anabolism. Researchers suggested future studies focusing on ribosomal biogensis and protein synthesis to counteract the impacts of high CO2 on skeletal muscles.

Investigating Abnormal Chromosome Tolerance in Wild Yeast Cells

Hose et al (2020) researched the genetic basis of aneuploidy tolerance in wild yeast in a recent edition of Elife.

Aneuploidy, or the abnormal chromosome numbers in a cell, is a harmful condition in developmental stages of wild yeast, yet is also common in plant cancers and pathogenic fungi. It is interesting to note that aneuploidy tolerance varies; for instance, researchers found that some wild isolates of baker’s yeast can tolerate chromosome amplification, while laboratory strains cannot. 

To study the genetic basis of how well wild yeast can tolerate aneuploidy, researchers mapped the genetic basis to Ssd1, an RNA-binding translational regulator that functions in wild strains but is defective in a laboratory strain “W303.” 

Researchers found that aneuploidy tolerance is enabled via a role for Ssd1 in mitochondrial physiology, such as binding and regulating nuclear-encoded mitochondrial mRNAs.


Transgenic animal models demonstrate that mice have similar COPD-related skeletal muscle dysfunction as humans

Balnis et al (2020) recently studied the mechanisms of COPD-related skeletal muscle dysfunction using an established transgenic animal model of COPD in a recently published paper in the Journal of Applied Physiology. 

Patients with chronic obstructive pulmonary disease (COPD), a disease that is characterized by obstructed airflow to the lungs and is associated with long-term exposure to cigarette smoke, often also develop skeletal muscle dysfunction. Overall, the comorbidity of COPD and skeletal muscle dysfunction is associated with outcomes such as poor health and mortality.

While some research has suggested that skeletal muscle dysfunction may be the result of COPD-related conditions, such as protein degradation and metabolic disruption, there is still poor understanding on what mechanisms would regulate these processes, as there is little to no research on a validated animal model of pulmonary emphysema. Therefore, Balnis et al (2020) sought to use such a model based on inducible UL-13-driven pulmonary emphysema (IL-13TG) to study the mechanisms of skeletal muscle dysfunction.

Using a transgenic mouse model, researchers found that the skeletal muscles of emphysematous mice are similar to those developed by human patients with COPD. For instance, both groups develop muscular atrophy and have decreased oxygen consumption. Within skeletal muscles, both groups also had downregulated ATP binding and bioenergetics.

Researchers concluded that transgenic animal models of COPD are useful to understand skeletal-muscle dysfunction in humans.

Software Highlight: LipidGenie

LipidGenie is one of many free and innovative resources offered by NCQBCS.

Lipid Genie is an interactive software that can facilitate lipid identification, provide evidence for gene function, and can reveal acyl-chain specificity for ABHD1 and ABHD2.

This open-sourced software is available free and online at lipidgenie.com.

Lipid Genie Logo. This logo depicts a magic lamp with a DNA helix inside, and a lipid structure exiting through the spout of the lamp.

Summer School Registration Closes Soon

Registration for the 3rd Annual North American Mass Spectrometry Summer School will close on March 1.

This means time is running out to sign up for 4 free days of learning, tutorial lectures, and hands-on-workshops– all led by world-leading experts in mass spectrometry.

The goal of this event– which will take place from June 15-18 at the Wisconsin Institute for Discovery– is to provide an engaging and inspiring program to students by combining networking, education and discovery and housing it all under one roof.

Specifically, this program covers the latest in application of mass spectrometry to omic analyses, from both industry and academic lenses. With tutorial lectures covering a variety of topics, from mass analyzers to lipidomics, and hands-on-workshops aimed at both scientific and professional development, this program is not one you would want to miss. Don’t forget to tell your peers about this excellent opportunity!

Registration is available at the following link: https://www.ncqbcs.com/resources/training/summer-school


A Strategy for Increasing Analytical Throughput in Quantitative Proteomics

Zhong et al (2019) developed a novel strategy aimed towards solving challenges in absolute quantification, and detailed these efforts in a recent issue of Analytical Chemistry.

Absolute quantification is both an effective technique– which allows for robust results in proteomics research– and a challenging one. Problems that absolute quantification presents include low specificity in complex backgrounds, limited analytical throughput and wide dynamic range.

To solve these issues, Zhong et al (2019) developed hybrid offset-triggered multiplex absolute quantification (HOTMAQ), a strategy which increases the analytical throughput (the increase in analysis production rate) of targeted quantitative proteomics by up to 12 times. This technique accomplishes this by using mass-difference and isobaric tags to create an internal standard curve in the MS1 precursor scan, identify peptides at the MS2 level, and mass offset-trigger the quantification of target proteins in synchronous precursor selection at the MS3 level. All of this is accomplished at the same time. 

Because HOTMAQ results in greater quantitative performance, higher flexibility and quicker analysis rate, HOTMAQ is a strategy that can easily be applied to target peptidomics, proteomics, and phosphoproteomics.

Graphical Abstract, demonstrating the technique of hybrid offset-triggered multiplex absolute quantification (HOTMAQ).  "Zhong, X., Q. Yu, F. Ma, D.C. Frost, L. Lu, Z. Chen, H. Zetterberg, C. Carlsson, O. Okonkwo, and L. Li,
Hotmaq: A multiplexed absolute quantification method for targeted proteomics. Analytical Chemistry,
2019. 91(3): p. 2112-2119. PMCID: PMC6379083"

3rd Annual North American Mass Spectrometry Summer School Registration Open

Join us for our third annual mass spectrometry summer school, which will be held in Madison, WI from June 15-18. We are proud to have assembled over a dozen world leading experts in mass spectrometry for this four-day course. Our goal is to provide our students, both from academia and industry, an engaging and inspiring program covering the latest in the application of mass spectrometry to omic analyses. Tutorial lectures range from mass analyzers to the basics of data analysis. Also planned are several hands-on workshops – aimed at both scientific and professional development. This program is made possible by generous funding from the National Science Foundation (Integrated Organismal Systems, Plant Genome Research Program, Grant No. 1546742) and the National Institutes of Health National Center for Quantitative Biology of Complex Systems (P41 GM108538). As such, there is no cost to participate.

Registration open through March 1, 2020: https://www.ncqbcs.com/resources/training/summer-school.

Please help us spread the word about this program by sharing the news with anyone who might have possible interest to participate.

See below for a list of expert instructors who will be leading the courses, as well as premium tutorial lectures and hands-on workshops that you can experience.

Thank you,
Josh Coon, Evgenia Shishkova, and Laura Van Toll (organizing committee)


Expert Instructors:

Scott McLuckey | Purdue University

Rachel Loo | University of California-Los Angeles

Joshua Coon | University of Wisconsin-Madison

Donald Hunt (invited) | University of Virginia

Shawnna Buttery | STAR Protocols

Jesper Velgaard Olsen | University of Copenhagen

Lingjun Li | University of Wisconsin-Madison

Jürgen Cox | Max Planck Institute of Biochemistry

Edward Huttlin | Harvard University

Susan Olesik | Ohio State University

Evgenia Shishkova | University of Wisconsin-Madison

Jessica Prenni | Colorado State University

Vicki Wysocki | Ohio State University

John Bowden | University of Florida

Tutorial Lectures:
Mass analyzers

Ionization

Tandem MS

Data acquisition

Quantification  

Experimental design

Separations  

PTMs

Metabolomics  

Top-down/Native MS

Lipidomics


Hands-on Workshops:
Mass analyzers

Spectral interpretation
Publishing and reviewing

Science writing

Science illustrations

Software Highlight: LipiDex

LipiDex is a free and open-source software package offered by NCQBCS. This software package unifies all stages of the LC-MS/MS lipid identification process, and also utilizes intelligent data filtering to reduce manual result curation while increasing identification confidence.

One can use LipiDex to accomplish a variety of functions. For instance, one can create and manage custom in-silico lipid spectral libraries; model complex lipid MS/MS fragmentation using intuitive fragmentation templates; generate high-confidence MS/MS lipid identifications; annotate chromatographic peak tables with lipid identifications; and automatically filter peak tables for adduct peaks, in-source fragments and dimers.

Information on both LipiDex and Library Forge can be found here, and the software download is located here. Additionally, information on other software that the National Center for Quantitative Biology of Complex Systems offers can be found here.

Graphical Abstract depicting the software package lipidex accomplishing a variety of functions, such as the modeling of complex lipid ms/ms fragmentation, generation of high-confidence ms/ms lipid identifications, annotation of chromatographic peak tables, and the creation of in-silico lipid spectral libraries.