Visual Abstract

Peter Lasch
Dec 1, 2020; 19:2125-2138
Technological Innovation and Resources

R. Greg Stacey
Nov 4, 2020; 0:RA120.002275v1-mcp.RA120.002275
Research

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

Over the past decade, modern methods of MS (MS) have emerged that allow reliable, fast and cost-effective identification of pathogenic microorganisms. Although MALDI-TOF MS has already revolutionized the way microorganisms are identified, recent years have witnessed also substantial progress in the development of liquid chromatography (LC)-MS based proteomics for microbiological applications. For example, LC-tandem MS (LC-MS²) has been proposed for microbial characterization by means of multiple discriminative peptides that enable identification at the species, or sometimes at the strain level. However, such investigations can be laborious and time-consuming, especially if the experimental LC-MS² data are tested against sequence databases covering a broad panel of different microbiological taxa. In this proof of concept study, we present an alternative bottom-up proteomics method for microbial identification. The proposed approach involves efficient extraction of proteins from cultivated microbial cells, digestion by trypsin and LC–MS measurements. Peptide masses are then extracted from MS¹ data and systematically tested against an in silico library of all possible peptide mass data compiled in-house. The library has been computed from the UniProt Knowledgebase covering Swiss-Prot and TrEMBL databases and comprises more than 12,000 strain-specific in silico profiles, each containing tens of thousands of peptide mass entries. Identification analysis involves computation of score values derived from correlation coefficients between experimental and strain-specific in silico peptide mass profiles and compilation of score ranking lists. The taxonomic positions of the microbial samples are then determined by using the best-matching database entries. The suggested method is computationally efficient – less than 2 mins per sample - and has been successfully tested by a test set of 39 LC-MS¹ peak lists obtained from 19 different microbial pathogens. The proposed method is rapid, simple and automatable and we foresee wide application potential for future microbiological applications.

We developed a simple and rapid method to enrich protein N-terminal peptides, in which the protease TrypN is first employed to generate protein N-terminal peptides without Lys or Arg and internal peptides with two positive charges at their N-termini, and then the N-terminal peptides with or without N-acetylation are separated from the internal peptides by strong cation exchange chromatography according to a retention model based on the charge/orientation of peptides. This approach was applied to 20 μg of human HEK293T cell lysate proteins to profile the N-terminal proteome. On average, 1,550 acetylated and 200 unmodified protein N-terminal peptides were successfully identified in a single LC/MS/MS run with less than 3% contamination with internal peptides, even when we accepted only canonical protein N-termini registered in the Swiss-Prot database. Since this method involves only two steps, protein digestion and chromatographic separation, without the need for tedious chemical reactions, it should be useful for comprehensive profiling of protein N-termini, including proteoforms with neo-N-termini.

Biological functions emerge from complex and dynamic networks of protein-protein interactions. Because these protein-protein interaction networks, or interactomes, represent pairwise connections within a hierarchically organized system, it is often useful to identify higher-order associations embedded within them, such as multi-member protein complexes. Graph-based clustering techniques are widely used to accomplish this goal, and dozens of field-specific and general clustering algorithms exist. However, interactomes can be prone to errors, especially when inferred from high-throughput biochemical assays. Therefore, robustness to network-level noise is an important criterion for any clustering algorithm that aims to generate robust, reproducible clusters. Here, we tested the robustness of a range of graph-based clustering algorithms in the presence of noise, including algorithms common across domains and those specific to protein networks. Strikingly, we found that all of the clustering algorithms tested here markedly amplified noise within the underlying protein interaction network. Randomly rewiring only 1% of network edges yielded more than a 50% change in clustering results, indicating that clustering markedly amplified network-level noise. Moreover, we found the impact of network noise on individual clusters was not uniform: some clusters were consistently robust to injected noise while others were not. To assist in assessing this, we developed the clust.perturb R package and Shiny web application to measure the reproducibility of clusters by randomly perturbing the network. We show that clust.perturb results are predictive of real-world cluster stability: poorly reproducible clusters as identified by clust.perturb are significantly less likely to be reclustered across experiments. We conclude that graph-based clustering amplifies noise in protein interaction networks, but quantifying the robustness of a cluster to network noise can separate stable protein complexes from spurious associations.

C-X-C motif chemokine receptor 4 (CXCR4)–directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [^99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [^99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52–1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [^99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [⁶⁸Ga]Ga-pentixafor PET.

Mattel has apologized after inadvertently directing customers of its new line of Wicked dolls to a pornographic website, stating it is taking action to remove the misprinted toys' packaging.

After much anticipation, the National Institute of Standards and Technology (NIST) issued its first Post Quantum Cryptography (PQC) standards today. They are intended to defeat efforts by quantum computers powerful […]

The post NIST Issues Post Quantum Cryptography Standards and Calls for their Adoption appeared first on HPCwire.

Yulia Lerner
Feb 23, 2011; 31:2906-2915
BehavioralSystemsCognitive

A new book reveals striking images from six decades of the beloved Wildlife Photographer of the Year competition

Transitions: Photographs by Robert Creamer

A museum in Portland, Oregon highlights the multi-layered path of 3D imagery, from stereoscopes of the American West to blockbuster movies

A close look reveals how the famed photographer altered his glass negatives, creating the popular image of Native Americans that still exists today

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Deep in the jungles of Brazil, photographer Steve Winter explains how he managed to capture stunning images of one of the world's top predators. Read more about jaguars at http://www.smithsonianmag.com/video/Photographing-the-Elusive-Jaguar.html

The National Gallery of Art organized a comprehensive exhibit of Robert Frank's work (Images courtesy of: National Gallery of Art; Produced by: Diane Bolz and Brian Wolly)

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After his start capturing the horrors of the Civil War for Mathew Brady's studio, 19th century photographer Timothy O'Sullivan uncovered the beauty of the great expanses of the American west

Read more at http://www.smithsonianmag.com/history-archaeology/We-Have-Liftoff.html Photographer David Burnett focused his camera on the many tourists who flocked to Florida in 1969 to watch the launch of Apollo 11 (Produced by Molly Roberts; Photographs by David Burnett/Contact Press Images).

Read more at http://www.smithsonianmag.com/arts-culture/In-Vogue.html At 62 years old, Edward Steichen convinced the U.S. Navy to let him gather a team of photographers to capture the men serving their country in the Pacific Ocean during World War II.

The annual contest unveiled its winners, highlighting avian photos that focus on conservation issues, the beauty of birds and their sometimes hilarious behavior

Breathtaking shots shine a light on the wonders of wildlife and the threats that human activities pose to the natural world

Take a virtual tour through the streets and sights of England’s capital city with these stunning travel photos submitted to our photo contest

Get acquainted with the Big Apple’s major sights by browsing through these remarkable travel photos submitted to our photo contest

Getting the perfect shot requires great timing, the right equipment and nerves of steel

The insect eggshell is a multifunctional structure with several important roles, including generating an entry point for sperm via the micropyle before oviposition, serving as an oviposition substrate attachment surface, and functioning as a protective layer during embryo development. Eggshell proteins play major roles in eggshell tanning and hardening following oviposition and provide molecular cues that define dorsal–ventral axis formation. Precise eggshell formation during ovarian follicle maturation is critical for normal embryo development and the synthesis of a defective eggshell often gives rise to inviable embryos. Therefore, simple and accurate methods for identifying eggshell proteins will facilitate our understanding of the molecular pathways regulating eggshell formation and the mechanisms underlying normal embryo development. This protocol describes how to isolate and enrich eggshells from mature oocytes of Aedes aegypti mosquitoes and how to extract their eggshell proteins for liquid chromatography with tandem mass spectrometry (LC–MS/MS) proteomic analysis. Although this methodology was developed for studying mosquito eggshells, it may be applicable to eggs from a variety of insects. Mosquitoes are ideal model organisms for this study as their ovarian follicle development and eggshell formation are meticulously regulated by blood feeding and their follicles develop synchronously throughout oogenesis in a time-dependent manner.

In a new biopic starring Kate Winslet, Miller's many lives—as an artist, model, muse, cook and war correspondent—need little embellishment

Hospice Northwest Services is inviting people to visit its third annual photography exhibit, "A Personal Lens on Grief." Here's what the project in Thunder Bay, Ont., entails, and why staff say it's important to find creative ways to express loss.

A man from Queens County has been sentenced to five years and nine months in federal prison for charges including making and transmitting child pornography, voyeurism and intercepting private communications.

SolidWorks CAD Software Enables Engineering Students to Fit ‘CubeSat’ Components Into a Four-Inch Square Box

Penn State Wilkes-Barre’s Friedman Art Gallery is preparing to open a new exhibit. “Photography of Protest” by photographer Michael Mirabito will open on Oct. 31 and continue until Dec. 3. The gallery is open on weekdays from 8 a.m. to 5 p.m.

A former dancer uses her choreography skills to plan her students' movement through the classroom.

Russian MPs on Tuesday passed in the final third reading controversial legislation banning "propaganda" of remaining childless, the latest measure targeting what Moscow depicts as Western liberal ideas.

Realme GT 7 Pro will launch in India on November 26 at 12pm IST. The phone was unveiled in China earlier this month. The Indian variant is expected to be similar to its Chinese counterpart. Now Realme has revealed several camera specifications and features of the Realme GT 7 Pro.

NASA's Roman Space Telescope has successfully integrated the Roman Coronagraph, a vital step in detecting planets far beyond our solar system. This tool will help block starlight, enabling the telescope to capture faint planetary light. The coronagraph marks a significant advancement in exoplanet detection, allowing the telescope to observe planets 100 million times fainter than their stars. The mission will provide insights into dark energy, exoplanets, and more, paving the way for future observatories like the Habitable Worlds Observatory.

On view through February 26, 2021 Visit the Gallery in-person or view it online Wilmington, Del. (February 3, 2021) –Anamnesis, an exhibition of photography by Bronwen Hazlett, is on view in the Mezzanine Gallery through February 26, 2021. Hazlett, a fine art photographer based in Clayton, is fluent in digital and analog photographic processes. Inspired […]

Ex-Tower Hill employee faces seven felonies; no Delaware children or THS students among known victims A Wilmington man and former Tower Hill School employee arrested in April has been indicted on charges arising from a child pornography investigation. William Ushler, 53, was arrested and charged on April 19 by members of the Department of Justice […]

A Seaford pastor has been arrested and charged with 10 felony counts of Dealing in Child Pornography, Attorney General Kathy Jennings announced Thursday.  James R. Dryden, 74, was arrested February 15 following an Internet Crimes Against Children Task Force (ICAC) investigation led by the Delaware Department of Justice and Delaware State Police. ICAC’s investigation was spurred […]

Conviction is State’s first use of updated “partial nudity” statute  A Wilmington man could spend the rest of his life in prison following a litany of felony convictions in a child pornography case. Sheldon Lee, 64, was convicted on May 16 of 50 felonies — 25 counts of Dealing in Child Pornography and 25 counts […]

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