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persister cell

Rui Santos, Catarina Costa, Dalila Mil-Homens, Daniela Romão, Carla C C R de Carvalho, Pedro Pais, Nuno P Mira, Arsénio M Fialho, Miguel C Teixeira
The mechanisms of persistence and virulence associated to Candida glabrata infections are poorly understood, limiting the ability to fight this fungal pathogen. In this study, the multidrug resistance transporters CgTpo1_1 and CgTpo1_2 are shown to play a role in C. glabrata virulence. The survival of the infection model Galleria mellonella, infected with C. glabrata, was found to increase upon the deletion of either CgTPO1_1 or CgTPO1_2. The underlying mechanisms were further explored. In the case of CgTpo1_1, this phenotype was found to be consistent with the observation that it confers resistance to antimicrobial peptides (AMP), such as the human AMP histatin-5...
October 25, 2016: Cellular Microbiology
Jürgen Dieker, Jo H Berden, Marinka Bakker, Jean-Paul Briand, Sylviane Muller, Reinhard Voll, Christopher Sjöwall, Martin Herrmann, Luuk B Hilbrands, Johan van der Vlag
Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features...
2016: PloS One
Ying Chen, Shuyan Cao, Pingping Xu, Wei Han, Tiankai Shan, Jingying Pan, Weiwei Lin, Xue Chen, Xiaodong Wang
BACKGROUND Results from DNA microarray experiments have shown that the expression of miR-34s undergoes significant changes following spinal cord injury (SCI). The present study was designed to detect changes in the expression of miR-34s and its target genes during the acute and sub-acute stages of SCI. MATERIAL AND METHODS Luxol fast blue (LFB) staining for myelin was used to observe the differences in the general morphology of the spinal cord after SCI in a contusion model in rats. qPCR was carried out to determine the expression variation of miR-34s and its target genes during the acute and sub-acute stages of SCI...
October 25, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Armando Arias, Lucy Thorne, Elsa Ghurburrun, Dalan Bailey, Ian Goodfellow
Intrahost genetic diversity and replication error rates are intricately linked to RNA virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. We have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. Given the role of replication fidelity and genetic diversity in pathogenesis, we have now investigated whether polymerase fidelity can also impact virus transmission between susceptible hosts...
September 2016: MSphere
Danielle Ahn, Hernán Peñaloza, Zheng Wang, Matthew Wickersham, Dane Parker, Purvi Patel, Antonius Koller, Emily I Chen, Susan M Bueno, Anne-Catrin Uhlemann, Alice Prince
Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6C(hi) monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers...
October 20, 2016: JCI Insight
Hobia Gole, Raymond Chuk, David Coman
Kabuki syndrome is a clinically and genetically heterogeneous congenital malformation syndrome with protean clinical manifestations. This reflects the important epigenetic role in embryonic development of the two genes currently known to be associated with Kabuki syndrome i.e., KMT2D and KDM6A, which are responsible for Kabuki syndrome 1 and Kabuki syndrome 2, respectively. Hypoglycemia is thought to be a rare manifestation of Kabuki syndrome; however it may be under diagnosed. Herein we describe the case of a 5-year-old girl with Kabuki syndrome 2 in whom persistent hyperinsulinism was diagnosed at 4 years of age...
August 8, 2016: Clinics and Practice
Satomi Miwa, Rafal Czapiewski, Tengfei Wan, Amy Bell, Kirsten N Hill, Thomas von Zglinicki, Gabriele Saretzki
Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased...
October 22, 2016: Aging
Yiqun Chen, Pengchao Xie, Zongping Wang, Ran Shang, Songlin Wang
The performance of UV-activated persulfate (UV/PS) technology as preoxidation process to enhance Microcystis aeruginosa removal by subsequent coagulation-sedimentation was firstly evaluated. The results demonstrate that UV/PS preoxidation could successfully promote coagulation of algae cells through the effective neutralization of zeta potential, which was caused by the changes of cell morphology, size distribution and surface properties after simultaneous UV irradiation and formed reactive species (i.e. SO4(-) and HO) oxidation...
October 11, 2016: Journal of Hazardous Materials
Louis J Imbriano, Joseph Mattana, James Drakakis, John K Maesaka
BACKGROUND: There is controversy over the prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral or renal salt wasting (RSW), 2 syndromes with identical common clinical and laboratory parameters but different therapies. The traditional approach to the hyponatremic patient relies on volume assessment, but there are limitations to this method. METHODS: We used an algorithm that relies on fractional excretion of urate (FEurate) to evaluate patients with hyponatremia and present 4 illustrative cases...
October 2016: American Journal of the Medical Sciences
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint...
October 24, 2016: Nature Immunology
Alexander Leithner, Alexander Eichner, Jan Müller, Anne Reversat, Markus Brown, Jan Schwarz, Jack Merrin, David J J de Gorter, Florian Schur, Jonathan Bayerl, Ingrid de Vries, Stefan Wieser, Robert Hauschild, Frank P L Lai, Markus Moser, Dontscho Kerjaschki, Klemens Rottner, J Victor Small, Theresia E B Stradal, Michael Sixt
Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation...
October 24, 2016: Nature Cell Biology
Brennan S Dirk, Logan R Van Nynatten, Jimmy D Dikeakos
Viruses must continuously evolve to hijack the host cell machinery in order to successfully replicate and orchestrate key interactions that support their persistence. The type-1 human immunodeficiency virus (HIV-1) is a prime example of viral persistence within the host, having plagued the human population for decades. In recent years, advances in cellular imaging and molecular biology have aided the elucidation of key steps mediating the HIV-1 lifecycle and viral pathogenesis. Super-resolution imaging techniques such as stimulated emission depletion (STED) and photoactivation and localization microscopy (PALM) have been instrumental in studying viral assembly and release through both cell-cell transmission and cell-free viral transmission...
October 19, 2016: Viruses
Cameron Browne
This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
M Ortega Escudero, J M Gutiérrez Dueñas, C Hernández Díaz, C Ruiz Hierro, R Chamorro Juárez, E Ardela Díaz
OBJECIVES: The aim of this study is to assess the outcome of surgery (Lynn's myectomy) in patients with chronic persistent constipation and failure of medical treatment. MATERIAL AND METHODS: Descriptive study of patients with severe chronic constipation treated by posterior anorectal myectomy (Lynn's technique). We report data from the last 15 years, with a minimum postoperative follow-up of one year. Patients included in the study suffered from a long-term constipation refractory to medical management...
October 10, 2016: Cirugía Pediátrica: Organo Oficial de la Sociedad Española de Cirugía Pediátrica
Takashi Dejima, Kenjiro Imada, Ario Takeuchi, Masaki Shiota, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Ladan Fazli, Seiji Naito, Martin E Gleave, Christopher J Ong
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy...
October 24, 2016: Prostate
Daria Matyushkina, Olga Pobeguts, Ivan Butenko, Anna Vanyushkina, Nicolay Anikanov, Olga Bukato, Daria Evsyutina, Alexandra Bogomazova, Maria Lagarkova, Tatiana Semashko, Irina Garanina, Vladislav Babenko, Maria Vakhitova, Valentina Ladygina, Gleb Fisunov, Vadim Govorun
What strategies do bacteria employ for adaptation to their hosts and are these strategies different for varied hosts? To date, many studies on the interaction of the bacterium and its host have been published. However, global changes in the bacterial cell in the process of invasion and persistence, remain poorly understood. In this study, we demonstrated phase transition of the avian pathogen Mycoplasma gallisepticum upon invasion of the various types of eukaryotic cells (human, chicken, and mouse) which was stable during several passages after isolation of intracellular clones and recultivation in a culture medium...
October 24, 2016: Scientific Reports
Yunes Panahi, Danial Roshandel, Mohammad Mehdi Sadoughi, Mostafa Ghanei, Amirhossein Sahebkar
Sulfur mustard (SM; mustard gas) is a classic chemical warfare agent that has been used in several wars and is still a potential threat especially in the Middle-East region. Victims experience acute symptoms in air-exposed organs including skin, respiratory tract and the eyes. Survivors of the acute stage might develop chronic or delayed-onset complications in the exposed organs. The exact mechanism(s) of SM-induced tissue damage is still unknown, however DNA alkylation and oxidative damage are the most relevant mechanisms...
October 21, 2016: Current Pharmaceutical Design
Sandugash Dyussenova, Bibigul Tukbekova, Saule Kizatova, V Tattigul, Karlygash Zhubanysheva, Kulzia Zhaktaeva, Saida Sadvakassova, Gulmira Serikova, V Nazym, Aiman Issayeva
Purpose was to assess the status of protein and lipid oxidative metabolism as a pathogenic link of acute rheumatic fever by measuring markers of early lesion. The analysis of lipid peroxidation and antioxidant protection indicators revealed unidirectional changes that confirm significant cellular membrane lesion. In addition, the determined changes correlated with the activity level of the pathological process while comparing the indicators of ill children in remission and during exacerbation. It was found that despite the active traditional treatment in hospitals for in-patients, a number of studied indicators did not return to normal in remission...
October 19, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
Anke Theil, Carmen Wilhelm, Matthias Kuhn, Andreas Petzold, Sebastian Tuve, Uta Oelschlägel, Andreas Dahl, Martin Bornhäuser, Ezio Bonifacio, Anne Eugster
T regulatory cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GvHD). However, our knowledge on in vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire and or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCRα-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer...
October 24, 2016: Clinical and Experimental Immunology
Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J Elrod, Khalidur Rahman, Chris C Ibegbu, Joseph F Magliocca, Andrew B Adams, Frank Anania, Arash Grakoui
: Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to non-functional intrahepatic CD8+ T cell responses. In light of dampened CD8+ T cell responses, liver disease often manifests systemically as Ig-related syndromes due to aberrant B cell functions. These two opposing yet co-existing phenomena implicate the potential of altered CD4+ T cell help. Elevated CD4+ Foxp3+ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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