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https://www.readbyqxmd.com/read/28542701/two-separate-effects-contribute-to-regulatory-t-cell-defect-in-sle-patients-and-their-unaffected-relatives
#1
Nuno Costa, Oriana Marques, Sandra I Godinho, Cláudia Carvalho, Barbara Leal, Ana M Figueiredo, Carlos Vasconcelos, António Marinho, Maria F Moraes-Fontes, António Gomes da Costa, Cristina Ponte, Raquel Campanilho-Marques, Telma Cóias, Ana R Martins, João F Viana, Margarida Lima, Berta Martins, Constantin Fesel
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#2
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28540820/theoretical-model-for-laser-ablation-outcome-predictions-in-brain-calibration-and-validation-on-clinical-mr-thermometry-images
#3
Samuel John Fahrenholtz, Reza Madankan, Shabbar Danish, John D Hazle, R Jason Stafford, David Fuentes
PURPOSE: Neurosurgical laser ablation is experiencing a renaissance. Computational tools for ablation planning aim to further improve the intervention. Here, global optimisation and inverse problems are demonstrated to train a model that predicts maximum laser ablation extent. METHODS: A closed-form steady state model is trained on and then subsequently compared to N = 20 retrospective clinical MR thermometry datasets. Dice similarity coefficient (DSC) is calculated to provide a measure of region overlap between the 57 °C isotherms of the thermometry data and the model-predicted ablation regions; 57 °C is a tissue death surrogate at thermal steady state...
May 19, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28539629/early-onset-mild-cognitive-impairment-in-parkinson-s-disease-altered-corticopetal-cholinergic-network
#4
Injoong Kim, Na-Young Shin, Yunjin Bak, Phil Hyu Lee, Seung-Koo Lee, Soo Mee Lim
Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson's disease (PD). We examined functional and structural patterns of SI degeneration in drug-naïve PD patients according to the duration of parkinsonism before mild cognitive impairment (MCI) diagnosis. Twenty PD patients with a shorter duration (PD-MCI-SD, <1 year), 18 patients with a longer duration (PD-MCI-LD, ≥1 year), and 29 patients with intact cognition (PD-IC) were included. Seed-based resting-state functional connectivity (rsFC) analysis using bilateral SI seed and region-of-interest-based volumetric analysis were performed...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28538176/tonic-lat-hdac7-signals-sustain-nur77-and-irf4-expression-to-tune-naive-cd4%C3%A2-t-cells
#5
Darienne R Myers, Tannia Lau, Evan Markegard, Hyung W Lim, Herbert Kasler, Minghua Zhu, Andrea Barczak, John P Huizar, Julie Zikherman, David J Erle, Weiguo Zhang, Eric Verdin, Jeroen P Roose
CD4(+) T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4(+) T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (TH2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537496/feeder-free-derivation-of-na%C3%A3-ve-human-pluripotent-stem-cells
#6
Emily Ward, Kirk Twaroski, Jakub Tolar
Human pluripotent stem cells (HPSCs) cultured in conditions that maintain pluripotency via FGF and TGFβ signaling have been described as being in a primed state. These cells have been shown to exhibit characteristics more closely related to mouse epiblast-derived stem cells than to so called naïve mouse PSCs said to possess a more ground state pluripotency that mimics the early mouse embryo inner cell mass. Initial attempts to create culture conditions favorable for generation of naïve HPSCs from primed HPSCs has required the use of mouse embryonic fibroblasts as a feeder layer to support this transition...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28537488/capturing-human-na%C3%A3-ve-pluripotency-in-the-embryo-and-in-the-dish
#7
Ludovic Zimmerlin, Tea Soon Park, Elias T Zambidis
Although human embryonic stem cells (hESC) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to post-implantation lineage-primed murine epiblast stem cells (EpiSC) than to naïve pre-implantation ICM-derived mouse embryonic stem cells (ESC). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESC and human induced pluripotent stem cells (hiPSC) appear to lack many of the defining hallmarks of naïve mouse ESC...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28530648/mechanism-of-human-somatic-reprogramming-to-ips-cell
#8
Rika Teshigawara, Junkwon Cho, Masahiro Kameda, Takashi Tada
Somatic reprogramming to induced pluripotent stem cells (iPSC) was realized in the year 2006 in mice, and in 2007 in humans, by transiently forced expression of a combination of exogenous transcription factors. Human and mouse iPSCs are distinctly reprogrammed into a 'primed' and a 'naïve' state, respectively. In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies...
May 22, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28529323/an-immunogenic-phenotype-in-paternal-antigen-specific-cd8-t-cells-at-embryo-implantation-elicits-later-fetal-loss-in-mice
#9
Lachlan M Moldenhauer, Kerrilyn R Diener, John D Hayball, Sarah A Robertson
Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8(+) T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8(+) T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen...
May 22, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28515300/a-novel-a-h7n2-influenza-virus-isolated-from-a-veterinarian-caring-for-cats-in-a-new-york-city-animal-shelter-causes-mild-disease-and-transmits-poorly-in-the-ferret-model
#10
Jessica A Belser, Joanna A Pulit-Penaloza, Xiangjie Sun, Nicole Brock, Claudia Pappas, Hannah M Creager, Hui Zeng, Terrence M Tumpey, Taronna R Maines
In December 2016, a low pathogenic avian influenza (LPAI) A(H7N2) virus was identified as the causative source of an outbreak in a cat shelter in New York City, which subsequently spread to multiple shelters in New York and Pennsylvania. One person with occupational exposure to infected cats became infected with the virus, representing the first LPAI H7N2 human infection in North America since 2003. Considering the close contact that frequently occurs between companion animals and humans, it was critical to assess the relative risk of this novel virus to public health...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28512473/vitamin-c-in-stem-cell-biology-impact-on-extracellular-matrix-homeostasis-and-epigenetics
#11
REVIEW
Cristina D'Aniello, Federica Cermola, Eduardo Jorge Patriarca, Gabriella Minchiotti
Transcription factors and signaling molecules are well-known regulators of stem cell identity and behavior; however, increasing evidence indicates that environmental cues contribute to this complex network of stimuli, acting as crucial determinants of stem cell fate. l-Ascorbic acid (vitamin C (VitC)) has gained growing interest for its multiple functions and mechanisms of action, contributing to the homeostasis of normal tissues and organs as well as to tissue regeneration. Here, we review the main functions of VitC and its effects on stem cells, focusing on its activity as cofactor of Fe(+2)/αKG dioxygenases, which regulate the epigenetic signatures, the redox status, and the extracellular matrix (ECM) composition, depending on the enzymes' subcellular localization...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28508054/flexible-adaptation-of-male-germ-cells-from-female-ipscs-of-endangered-tokudaia-osimensis
#12
Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Mizuho Inokuchi, Kimiko Honsho, Ah-Reum Lee, Hiroki Nabekura, Hiroshi Ohta, Tomoyuki Tsukiyama, Yasuhide Ohinata, Asato Kuroiwa, Yoshitaka Hishikawa, Mitinori Saitou, Takamichi Jogahara, Chihiro Koshimoto
In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis, it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28507921/sofosbuvir-based-regimens-with-task-shifting-is-cost-effective-in-expanding-hepatitis-c-treatment-access-in-the-united-states
#13
Channa R Jayasekera, Rachel Beckerman, Nathaniel Smith, Ryan B Perumpail, Robert J Wong, Zobair M Younossi, Aijaz Ahmed
Background and Aims: The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection (HCV) is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United States. Task shifting-whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians-achieves non-inferior treatment outcomes with second generation direct-acting antivirals (2(nd) Gen DAAs), may increase treatment capacity, and may facilitate greater treatment access...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507549/human-lung-mononuclear-phagocytes-in-health-and-disease
#14
REVIEW
Faezzah Baharom, Gregory Rankin, Anders Blomberg, Anna Smed-Sörensen
The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs)-together termed mononuclear phagocytes (MNPs)-line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28489763/naturally-occurring-drug-resistance-associated-variants-to-hepatitis-c-virus-direct-acting-antiviral-agents-in-treatment-naive-hcv-genotype-1b-infected-patients-in-china
#15
Zhanyi Li, Ying Zhang, Ying Liu, Xiaoqiong Shao, QiuMin Luo, Qingxian Cai, Zhixin Zhao
The direct-acting antiviral agents (DAAs) have drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the resistance-associated variants (RAVs) to DAAs may hamper treatment. There was a lack of data on the prevalence of pre-exist RAVs in Chinese HCV-infected patients. We performed nested PCR assays on 74 HCV genotype 1b-infected patients to amplify HCV viral regions of NS3, NS5A, and NS5B to investigate the prevalence of RAVs to DAAs in treatment-naive HCV genotype1b-infected patients in China...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28483096/electroencephalogram-alpha-to-theta-ratio-over-left-fronto-temporal-region-correlates-with-negative-symptoms-in-schizophrenia
#16
Sayantanava Mitra, Shamsul Haque Nizamie, Nishant Goyal, Sai Krishna Tikka
BACKGROUND: Negative symptoms impair outcomes on occupational functioning, social interaction and interpersonal relationships in patients with schizophrenia. Past researchers have reported reduced alpha and increased theta and delta spectral powers on quantitative EEG recordings in those with prominent negative symptoms. AIM: Present analysis aimed at exploring the relationships between lower-frequency EEG powers and negative symptoms, in schizophrenia, over a period of naturalistic antipsychotic treatment...
April 2017: Asian Journal of Psychiatry
https://www.readbyqxmd.com/read/28476336/abnormal-neural-activity-as-a-potential-biomarker-for-drug-naive-first-episode-adolescent-onset-schizophrenia-with-coherence-regional-homogeneity-and-support-vector-machine-analyses
#17
Yi Liu, Yan Zhang, Luxian Lv, Renrong Wu, Jingping Zhao, Wenbin Guo
BACKGROUND: Patients with adolescent-onset schizophrenia (AOS) hold the same but severe form of symptoms with adult-onset schizophrenia, and with worse outcome and poor treatment response to antipsychotics. Several dominant brain regions of schizophrenia patients show significantly abnormal structural and functional connectivity during resting-state scans. However, coherence regional homogeneity (Cohe-ReHo) in drug-naive first-episode patients with AOS remains unclear. METHOD: A total of 48 drug-naive first-episode AOS outpatients and 31 healthy controls underwent resting-state functional magnetic resonance scans...
May 2, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28472324/cost-effectiveness-of-palbociclib-in-hormone-receptor-positive-advanced-breast-cancer
#18
H Mamiya, R K Tahara, S M Tolaney, N Choudhry, M Najafzadeh
BACKGROUND: Palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6 for the treatment of advanced breast cancer, has demonstrated significant efficacy in prolonging progression-free survival when added to existing therapies. Considering the high cost of palbociclib, we assessed cost-effectiveness of adding palbociclib to usual care in treatment of advanced breast cancer. METHODS: We developed a discrete event simulation model to simulate time to cancer progression and to compare life time clinical benefit and cost of alternative treatment strategies for patients with metastatic disease from societal perspective...
May 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28469817/no-relationship-between-baseline-salivary-alpha-amylase-and-state-trait-anxiety-inventory-score-in-drug-na%C3%A3-ve-patients-with-short-illness-duration-first-episode-major-depressive-disorder-an-exploratory-study
#19
Joanna Szarmach, Wiesław-Jerzy Cubała, Jerzy Landowski, Anna Chrzanowska
BACKGROUND: Salivary α-amylase (sAA) activity alternations are observed in major depressive disorder (MDD) being associated with depression severity and its specific psychopathological dimensions with anxiety being attributed to distress. No data is available on sAA in MDD according to Hamilton Rating Scale for Depression (HAMD-17) and State-Trait Anxiety Inventory (STAI). The exploratory study examines whether and to what extent baseline sAA level is interrelated to the psychopathological features including severity of symptoms and specific psychopathological dimensions...
April 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28469092/transcriptional-dissection-of-melanoma-identifies-a-high-risk-subtype-underlying-tp53-family-genes-and-epigenome-deregulation
#20
Brateil Badal, Alexander Solovyov, Serena Di Cecilia, Joseph Minhow Chan, Li-Wei Chang, Ramiz Iqbal, Iraz T Aydin, Geena S Rajan, Chen Chen, Franco Abbate, Kshitij S Arora, Antoine Tanne, Stephen B Gruber, Timothy M Johnson, Douglas R Fullen, Leon Raskin, Robert Phelps, Nina Bhardwaj, Emily Bernstein, David T Ting, Georg Brunner, Eric E Schadt, Benjamin D Greenbaum, Julide Tok Celebi
BACKGROUND: Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS: We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts...
May 4, 2017: JCI Insight
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