Research, Research Articles
Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis
Yen-Han Tseng1,2, Sheng-Wei Pan1,2,3, Jhong-Ru Huang2,4, Chang-Ching Lee1, Jung-Jyh Hung2,5, Po-Kuei Hsu2,5, Nien-Jung Chen6, Wei-Juin Su2,7, Yuh-Min Chen1,2 and Jia-Yih Feng1,2,8
The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of tuberculosis. Here we show that PD-L1 expression is increased in patients with active tuberculosis and is correlated with treatment outcomes.
Quantification methods of Candida albicans are independent irrespective of fungal morphology
Amanda B Soares1, Maria C de Albuquerque1, Leticia M Rosa1, Marlise I Klein 2, Ana C Paravina1, Paula A Barbugli1, Livia N Dovigo3 and Ewerton G de O Mima1
Our study demonstrated that the quantification methods of C. albicans (cells/mL, CFU/mL, and vPCR) did not agree, regardless of the fungal morphology/growth, even though a significant and strong correlation is observed.
Pathogenic Escherichia coli change the adhesion between neutrophils and endotheliocytes in the experimental bacteremia model
Svetlana N Pleskova1,2,*, Nikolay A Bezrukov1, Sergey Z Bobyk1, Ekaterina N Gorshkova1 and Dimitri V Novikov3
In this work, we have demonstrated that in the model of experimental septicemia there is a disruption of adhesion contacts between neutrophils and endothelial cells, manifested by a decrease in adhesion force and work upon exposure to E. coli.
Arsenite treatment induces Hsp90 aggregates distinct from conventional stress granules in fission yeast
Naofumi Tomimotoa, Teruaki Takasakia and Reiko Sugiura
Given the conserved role of Hsp90 as a molecular chaperone protein, our findings presented in this study may suggest a novel type of arsenite-induced biological condensates, wherein Hsp90 plays a key role in maintaining its integrity.
Unresolved mystery of cyclic nucleotide second messengers, periplasmic acid phosphatases and bacterial natural competence
Kristina Kronborg and Yong Everett Zhang
In this study we aimed to identify the promotors responsible for the expression of the non-specific acid phosphatase AphA during different starvation conditions, to confirm the requirement of the cAMP-dependent CRP regulon for aphA expression, and to finally identify regulators of its expression.
Expansion of metabolically labelled endocytic organelles and cytoskeletal cell structures in Giardia lamblia using optimised U- ExM protocols
Clirim Jetishi1,2,a, Erina A. Balmer1,2,a, Bianca M. Berger1,2,a, Carmen Faso1,3,4 and Torsten Ochsenreiter1
Understanding cellular ultrastructure is tightly bound to microscopic resolution and the ability to identify individual components at that resolution. In this study we demonstrate mostly isotropic 4.5-fold expansion of several different compartments in Giardia cells and present an optimised, shortened, and modular protocol that can be swiftly adjusted to the investigators needs.
Polyadenylated versions of small non-coding RNAs in Saccharomyces cerevisiae are degraded by Rrp6p/Rrp47p independent of the core nuclear exosome
Anusha Chaudhuri1,#, Soumita Paul2,#, Mayukh Banerjea2 and Biswadip Das2
In this investigation, we unveiled a novel functional role of the major nuclear 3′→5′ exoribonuclease, Rrp6p, and its cofactor Rrp47p in the degradation of polyadenylated versions of several mature sncRNAs, including 5S, 5.8S rRNAs, all sn- and some select snoRNAs in the baker’s yeast S. cerevisiae.
Exploring carbon source related localization and phosphorylation in the Snf1/Mig1 network using population and single cell-based approaches
Svenja Braam1, Farida Tripodi2, Linnea Österberg1,3, Sebastian Persson1, Niek Welkenhuysen1, Paola Coccetti2 and Marija Cvijovic1
In this work we set out to explore the relationship between the subcellular localization and regulation of kinases in the context of carbon source signaling. The data presented in this paper reinforce the notion that not only the activation/inactivation of kinases but also their subcellular localization and that of their targets influence fate decisions in response to environmental changes.
A Modular Cloning Toolkit for the production of recombinant proteins in Leishmania tarentolae
Katrin Hieronimus1,2,#, Tabea Donauer1,2,#, Jonas Klein1,#, Bastian Hinkel1,#, Julia Vanessa Spänle1,#, Anna Probst1,#, Justus Niemeyer1,#, Salina Kibrom1, Anna Maria Kiefer1, Luzia Schneider2, Britta Husemann2, Eileen Bischoff2, Sophie Möhring2, Nicolas Bayer1, Dorothée Klein1, Adrian Engels1, Benjamin Gustav Ziehmer2, Julian Stieß3, Pavlo Moroka1, Michael Schroda1, and Marcel Deponte2
Modular Cloning (MoClo) is based on libraries of standardized genetic parts that can be directionally assembled via Golden Gate cloning in one-pot reactions into transcription units and multigene constructs. We established a MoClo toolkit and exemplified its application for the production of recombinant proteins in L. tarentolae.
Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging
March 3, 2016
Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. The authors show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Their results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures.
Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity
February 19, 2016
Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.
Mitochondrial proteomics of the acetic acid – induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii – derived hybrid strain
January 22, 2016
Very high concentrations of acetic acid at low pH induce programmed cell death (PCD) in both the experimental model Saccharomyces cerevisiae and in Zygosaccharomyces bailii, the latter being considered the most problematic acidic food spoilage yeast due to its remarkable intrinsic resistance to this food preservative. This study offers insights into the mechanisms involved in acetic acid - induced PCD in the Z. bailii-derived hybrid strain ISA1307 by analyzing the yeast mitochondrial protein expression profile of cells challenged by acetic acid.
The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae
January 18, 2016
Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.
Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs
January 18, 2016
The formation of small Aβ42 oligomers has been implicated as a toxic species in Alzheimer disease (AD). Here, we show that the mechanism of the PICALM, human AD risk factor, is likely to reduce the level of Aβ42 oligomers in cells. We screened FDA-approved drugs to identify candidates that prevent the formation of Aβ42 small oligomers using the yeast Aβ42-RF reporter system. We also showed that each of the drug hits counteract yeast and mammalian cell toxicity associated with Aβ42 small aggregates.
Global translational impacts of the loss of the tRNA modification t6A in yeast
December 18, 2015
The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. Analysis of codon occupancy rates suggests that one of the major roles of t6A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I34:C3 pairs while increasing the elongation rate of rare tRNAs and G34:U3 pairs. This work reveals that the consequences of t6A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.
Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes
December 11, 2015
The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
November 13, 2015
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
November 11, 2015
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.