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We offer a selection of recent papers on a variety of topics from the Journal of Biological Chemistry, the Journal of Lipid Research and Â鶹´«Ã½É«ÇéƬ & Cellular Proteomics.

Peering into Alzheimer’s protein aggregation

The hereditary Arctic mutation of 42-amino-acid beta-amyloid peptide, known as Abeta42, causes aggressive aggregation of the peptide in early-onset Alzheimer’s disease. The mechanism connecting this mutation to the protein accumulation is unknown, however. Meng Lu and colleagues at the University of Cambridge revealed details of this process by establishing stable cell lines expressing the mutation and observing them with fluorescence-lifetime and super-resolution imaging. They found that Arctic mutant Abeta42 formed five unique types of aggregates that degraded more slowly than those in wild-type cells. The authors suggest their model lays groundwork for studying how intracellular amyloid affects cellular compartments. was published in the Journal of Biological Chemistry.

Advancing phage proteomics

Bacteriophages, or phages, are viruses that infect bacteria, and they are ubiquitous across the planet. Phage studies have provided fundamental knowledge for the development of molecular biology and important biotechnologies such as the CRISPR-Cas system.

Researchers are working to unravel crucial aspects of phage biology, including the phage and bacterial proteome during infection. Transcriptomic and metabolomic studies have been conducted to analyze gene expression during phage infection, but proteomic analysis is required to understand how gene expression is regulated post-transcription.

In published in Â鶹´«Ã½É«ÇéƬ & Cellular Proteomics, Marie-Laurence Lemay and colleagues from Laval University in Quebec City describe how they used high-throughput proteomics techniques to characterize the viral and bacterial proteomes at different stages of infection. They identified several bacterial proteins that were expressed only during infection. Their results also generated a more comprehensive view of the phage proteome that will be important for future studies of phage biology.

Up close and personal with ribosomes

The ability to visualize macromolecular structures of single cells could aid understanding of a host of cellular activities. However, current methods are limited by low resolution and the requirement for highly purified samples. Xiunan Yi and colleagues at the University of Texas present a new technique that combines single-cell lysis with electron microscopy. In in the Journal of Biological Chemistry, they write that they used this method to image and count ribosomes of single Caenorhabditis elegans embryos throughout several stages of development. The authors conclude that this method holds significant promise for applications in developmental, evolutionary and disease-related studies.

High fructose diet and metabolic syndrome

Have you looked at the sugar content on your favorite soft drink or juice? Soft drinks and juices are high in fructose. A high-fructose diet can lead to dyslipidemia and is a major risk factor for development of cardiovascular disease, or CVD, and insulin resistance. Andrew Butler at Saint Louis University, in collaboration with researchers at the University of California, Davis, studied the role of fructose-fed diet in developing CVD. In published in the Journal of Lipid Research, they write that they fed rhesus monkeys beverages sweetened with fructose-containing sugar and measured plasma lipid profiles as well as lipidomic changes. They were the first researchers to show a positive correlation between high fructose consumption and an increase in the quantity of large lipoprotein particles such as very-low density lipoproteins, known as VLDLs, that are associated with CVD. Furthermore, they showed that administration of fish oil reversed the increased shift in the quantity of large lipoprotein particles. They showed a strong correlation between concentration of plasma ApoC3, a protein component of VLDLs, and elevation in the number of VLDLs. ApoC3 affects the metabolism of lipoproteins, and its expression is a risk factor for CVD. Next time, check the sugar content and think twice before you enjoy your favorite sweet drink.

Bacterial extracellular vesicles as virulent bombs

The bacterium Listeria monocytogenes is the cause of listeriosis, an illness that can present a major threat to pregnant women, newborns and others with weakened immune systems. This organism has been found to secrete tiny lipid-bilayered spheres called extracellular vesicles, or EVs, but their role in infection is not completely understood. Caroline Coelho at Johns Hopkins University and colleagues in the Journal of Biological Chemistry that these EVs contain several virulence factors including the pore-forming toxin listeriolysin O. High-resolution fluorescence imaging captured real-time EV release from bacteria inside infected mammalian cells. The authors suggest that EVs are used for toxin release, which adds to the current understanding of L. monocytogenes’ pathogenic strategy.

Immunomic screening of the Plasmodium proteome

Malaria is caused by a single-celled eukaryotic parasite in the Plasmodium genus. This parasite is spread from mosquitoes to humans, particularly in tropical and subtropical regions of the world, leading to severe disease and sometimes death. No vaccine exists to prevent malaria, and drug resistance poses a major threat to fighting the infection.

Developing a malaria vaccine has proved challenging, and additional studies are needed to identify new parasite proteins associated with protection in humans. A limited number of malaria proteins have been investigated, and a more comprehensive screening of the malaria proteome using antibodies able to provide protection against infection could advance vaccine development.

In published in Â鶹´«Ã½É«ÇéƬ & Cellular Proteomics, Anthony Siau and colleagues from the Nanyang Technological University in Singapore screening of the malaria proteome using antibodies able to provide protection against infection. After the initial screen, the researchers used predictive criteria to calculate the likelihood of protection for each antigen. Their proteomic techniques for studying protection provided a framework for the development of a new approach to malaria vaccine development.

Lipid profiles and chronic kidney disease

Data on the association between dyslipidemia and end-stage renal disease, the final stage of chronic kidney disease, are rare, and the results are not conclusive. Such data would be valuable for a medical practitioner putting a CKD patient on a drug regimen. Ching-Wei Tsai and colleagues at China Medical University performed a 13-year prospective study of more than 4,500 patients with CKD between the ages of 20 and 90 to find the association between lipid trajectories and risk of developing ESRD. In published in the Journal of Lipid Research, Tsai and colleagues report that higher baseline levels of lipoproteins such as LDL cholesterol and total cholesterol correlated with higher risk of developing ESRD in patients with CKD. Overall, the incidence of ESRD in CKD patients with high baseline triglyceride was 49 percent higher.

A protein that propelled life toward multicellularity

The basement membrane, or BM, is an extracellular matrix component that is essential to tissue functions. BM played a key role in the evolutionary leap of unicellular organisms to multicellularity, but its exact structure and function during this ancient transition are unknown. Carl Darris and colleagues at Vanderbilt University now report that the BM protein Goodpasture antigen-binding protein, or GPBP, likely played a key role in this transition. By comparing the genomes of some metazoans and unicellular organisms, they found that GPBP-2 is the oldest isoform of GPBP and possibly functioned both intracellularly and extracellularly in early metazoans. The GPBP-1 isoform emerged later in chordates as an extracellular component, which the authors suggest likely allowed for the development of epithelial tissues. were published in the Journal of Biological Chemistry.

Linking lipid transport to metabolic disease

Mutations in lipid transporting phospholipid flippases, or P4-ATPases, can lead to a variety of metabolic diseases, including insulin resistance and obesity. These mutants also have been associated with elevated levels of intracellular glucosylceramide, known as GlcCer, but how these lipids traverse cellular membranes is not well understood. In in the Journal of Biological Chemistry, Bartholomew Roland and colleagues from Vanderbilt University and Kyoto University confirmed that certain P4-ATPases play a direct role in GlcCer transport by observing uptake of fluorescently tagged GlcCer into yeast and human cells. They also found that a central glutamine of the TM4 transmembrane segment is required for GlcCer transport. The authors suggest that certain GlcCer-transporting P4-ATPases may be critical for lipid homeostasis and metabolism.