Research, Research Articles

A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus

Fangfang Li1, Peixi Qin1, Lisha Ye1, Nishith Gupta1,2,3 and Min Hu1

The herein presented results show a BMP-like receptor-regulated SMAD in Haemonchus contortus that is required for larval differentiation and underscore an adaptive functional repurposing of BMP-signaling in parasitic worms.

Nutrient sensing and cAMP signaling in yeast: G-protein coupled receptor versus transceptor activation of PKA

Griet Van Zeebroeck1,2,†, Liesbeth Demuyser1,2,†, Zhiqiang Zhang1,2, Ines Cottignie1,2 and Johan M. Thevelein1,2

The herein presented work supports a model, in which nutrient transceptors are evolutionary ancestors of GPCRs, employing a more primitive direct signaling mechanism compared to the indirect cAMP second-messenger signaling mechanism used by GPCRs for activation of PKA.

Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts

Rintaro Tsuchikado1,#, Satoshi Kami1,#, Sawako Takahashi1 and Hiromi Nishida1

In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.

Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast

Alissa D. Clear1,2,3, Glenn M. Manthey1,2, Olivia Lewis4,5, Isabelle Y. Lopez4,6, Rossana Rico4,7, Shannon Owens8,9, M. Cristina Negritto10, Elise W. Wolf10,11, Jason Xu10,12, Nikola Kenjić13, J. Jefferson P. Perry13, Aaron W. Adamson14, Susan L. Neuhausen14, Adam M. Bailis1,2,15

RAD52 is a key protein in DNA repair and suppresses DNA damage in yeast; however, certain variants affecting BRCA2 mutations fail to correct HRR defects. This suggests that HsRAD52 aids multiple DNA repair mechanisms and could be targeted for use in treating BRCA2-deficient cancers.

Systematic analysis of nuclear gene function in respiratory growth and expression of the mitochondrial genome in S. cerevisiae

Maria Stenger1, Duc Tung Le1, Till Klecker1 and Benedikt Westermann1

Using yeast Saccharomyces cerevisiae, the authors identified 254 nuclear genes essential for respiratory growth and 12 required for viability without mtDNA. They also found 176 genes involved in mitochondrial protein synthesis and mtDNA maintenance, offering a comprehensive view of the processes supporting oxidative phosphorylation.

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage

Pedro Ortega1, Desiré García-Pichardo1, Marta San Martin-Alonso1, Ana G. Rondón1, Belén Gómez-González1 and Andrés Aguilera1

This study reveals that conserved residues H3E73 and H4E53 in histones H3 and H4 play a crucial role in maintaining genome stability. Mutations at these sites increase recombinogenic DNA damage, likely due to replication-associated issues rather than transcriptional activity, highlighting their importance in DNA damage prevention and repair.

Sulforaphane alters the acidification of the yeast vacuole

Alexander Wilcox1,#, Michael Murphy1,#, Douglass Tucker1,#, David Laprade1, Breton Roussel1, Christopher Chin2, Victoria Hallisey1, Noah Kozub1, Abraham Brass2 and Nicanor Austriaco1

This study identifies vacuolar pH regulation as a key factor in sulforaphane (SFN) sensitivity, showing that SFN-induced cell death in yeast - and potentially in human cancer cells - is linked to its ability to raise vacuolar or lysosomal pH.

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids

Edruce Edouarzin1, Connor Horn2, Anuja Paudyal2, Cunli Zhang1, Jianyu Lu1, Zongbo Tong1, Guri Giaever3, Corey Nislow3, Raja Veerapandian2, Duy H. Hua1 and Govindsamy Vediyappan2

This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.

Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae

Jutta Diessl1, Arpita Nandy1, Christina Schug1, Lukas Habernig1 and Sabrina Büttner1,2

This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.

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An adenine model of inborn metabolism errors alters TDP-43 aggregation and reduces its toxicity in yeast revealing insights into protein misfolding diseases

May 22, 2025

This work offers new insights into the potential interactions between me-tabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.

Microbiota and metabolome dynamics induced by Shiga toxin-producing E. coli in an in vitro model of an infant’s colon

April 14, 2025

This study provides new evidence of the impact of EHEC in the microbiota and metabolome dynamics in an in vitro gut model that could be useful in understanding their physiopathology in this at-risk population, considering inter-individual variabilities in gut microbiota.

Ampicillin treatment in persister cell studies may cause non-physiological artifacts

March 20, 2025

This study shows at the example of L2 how insufficient purification of ampicillin persister cells can lead to the generation of non-physiological artifacts and provides a novel tool to improve the removal of residual cell debris.

Clostridium scindens promotes gallstone formation by inducing intrahepatic neutrophil extracellular traps through CXCL1 produced by colonic epithelial cells

March 19, 2025

Through in vivo and in vitro experiments, we validated the reliability of C. scindens stimulating colonic epithelial cells to produce TLR2, activating the NF-κB signaling pathway, promoting CXCL1 expres-sion, and inducing intrahepatic neutrophil NETosis, which may be associated with gallstone formation.

Integrative Omics reveals changes in the cellular landscape of peroxisome-deficient pex3 yeast cells

February 20, 2025

To uncover the consequences of peroxisome deficiency, we compared Saccharomyces cerevisiae wild-type with pex3 cells, which lack peroxisomes, employing quantitative proteomics and transcriptomics technologies.

Microwave-assisted preparation of yeast cells for ultrastructural analysis by electron microscopy

November 18, 2024

Budding yeast Saccharomyces cerevisiae is widely used as a model organism to study the biogenesis and architecture of organellar membranes, which can be visualized by transmission electron microscopy (TEM).

A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines

October 8, 2024

Given the common tropism of SARS-CoV-2 and RSV, and the unclear consequences of their mutual influence, we developed an in vitro lung epithelial cell model to study the molecular mechanisms and cellular pathways modulated in viral co-infection.

RidA proteins contribute to fitness of S. enterica and E. coli by reducing 2AA stress and moderating flux to isoleucine biosynthesis

October 4, 2024

This study solidifies the established role of RidA in removing 2AA, while also presenting evidence for a role of RidA in enhancing flux towards isoleucine biosynthesis in E. coli. Overall, these data emphasize that metabolic networks can generate distinct responses to perturbation, even when the individual components are conserved.

Fecal gelatinase does not predict mortality in patients with alcohol-associated hepatitis

August 26, 2024

This study aimed to investigate the significance of fecal gelatinase on clinical outcomes in patients with alcohol-associated hepatitis. In conclusion, in our cohort, fecal gelatinase does not predict mortality and does not indicate higher disease severity in patients with alcohol-associated hepatitis.

Direct detection of stringent alarmones (pp)pGpp using malachite green

August 5, 2024

In this study, we demonstrate the surprising discovery of a commercially available, low-cost malachite green (MG) detection kit, originally designed for orthophosphate (Pi) detection, for detecting (p)ppGpp and its analogues, especially pGpp

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