Research, Research Articles
Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma
Shuo Shi1, Yuwen Chu2,3, Haiyan Liu4,5, Lan Yu6,7,8, Dejun Sun8,9, Jialiang Yang2,3,5, Geng Tian2,3, Lei Ji2,3, Cong Zhang10 and Xinxin Lu11
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
Two TonB-dependent outer membrane transporters involved in heme uptake in Anabaena sp. PCC 7120
Julia Graf1, Martin Schöpperle1,2, Rafael Pernil1 and Enrico Schleiff1,3,4
Low availability of micronutrients such as iron has enforced the evolution of uptake systems in all kingdoms of life. In our study, we conclude that heme transport might not be restricted to Anabaena, but at the same time is not specific to a cyanobacterial order and thus might be related to the habitat of origin, a notion which needs to be challenged in the future.
The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit
Yiannis Pyrris1, Georgia F. Papadaki1, Emmanuel Mikros2 and George Diallinas1,3
FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.
Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation
Elisabetta de Alteriis1, Guido Incerti2, Fabrizio Cartenì3, Maria Luisa Chiusano3, Chiara Colantuono3, Emanuela Palomba4, Pasquale Termolino4, Francesco Monticolo3,5, Alfonso Esposito3, Giuliano Bonanomi3,6, Rosanna Capparelli3, Marco Iannaccone3,7, Alessandro Foscari2, Carmine Landi8, Palma Parascandola8, Massimo Sanchez9, Valentina Tirelli9, Bruna de Falco3, Virginia Lanzotti3 and Stefano Mazzoleni3,6
Our study demonstrates that extracellular DNA released by living cells can impact the growth rate of Saccharomyces cerevisiae cultures, showing similarities to extrachromosomal circular DNA and leading to cell cycle arrest in the S phase, suggesting potential new functional roles of exDNA.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
Paulina Katarzyna Grucela1 and Yong Everett Zhang1
The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.
Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues
Nitu Saha1, Swati Swagatika1 and Raghuvir Singh Tomar1
Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants
The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella
Lahiru Malalasekara1 and Jorge C. Escalante-Semerena1,*
Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.
Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2
Meike Arend1, Koray Ütkür1, Harmen Hawer1, Klaus Mayer2, Namit Ranjan3, Lorenz Adrian4, Ulrich Brinkmann2 and Raffael Schaffrath1
We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.
Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates
Steve Brunette1,#, Anupam Sharma1,2,#, Ryan Bell1, Lawrence Puente1 and Lynn A Megeney1,2,3,*
Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.
Impact of histone H4K16 acetylation on the meiotic recombination checkpoint in Saccharomyces cerevisiae
December 4, 2016
In meiotic cells, the pachytene checkpoint or meiotic recombination checkpoint is a surveillance mechanism that monitors critical processes, such as recombination and chromosome synapsis, which are essential for proper distribution of chromosomes to the meiotic progeny. We report here that Sas2-mediated acetylation of histone H4 at lysine 16 (H4K16ac) modulates meiotic checkpoint activity in response to synaptonemal complex defects. Our results reveal that proper levels of H4K16ac orchestrate this meiotic quality control mechanism and that Sir2 impinges on additional targets to fully activate the checkpoint.
The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription
November 5, 2016
The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.
Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets
August 30, 2016
In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.
VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
August 25, 2016
Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.
Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging
July 26, 2016
Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.
Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis
June 30, 2016
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.
Construction and evaluation of yeast expression networks by database-guided predictions
May 10, 2016
DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.
Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii
May 1, 2016
Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.
Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells
April 13, 2016
Actin filaments form cortical patches and emanating cables in fermenting cells of Saccharomyces cerevisiae. We assume that stability of actin cables reflects the metabolic status of the cell. Based on comparison of live and formaldehyde-fixed cells, our data suggest that formaldehyde affects respiration before fixation and this uneven signaling results in destabilization of actin cables in glucose-deprived cells.
Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1
March 22, 2016
The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. This study aimed to use the dynamin-like protein Vps1 of Saccharomyces cerevisiae as a model to gain insights into the mechanistic defects caused by specific dynamin mutations considered to underlie a number of diseases.