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Jing Wang, Sichen Liu, Baidong Hou, Meixiang Yang, Zhongjun Dong, Hai Qi, Wanli Liu
Class-switch recombination (CSR) and somatic hypermutation (SHM) occur during the differentiation of germinal center B cells (GCBs). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GCBs. Here, we show that ablation of PTEN through the Cγ1-Cre mediated recombination significantly influences the CSR and SHM responses. The GCs fail to produce the IgG1 B cells, the high affinity antibodies and nearly lost the dark zone (DZ) in Ptenfl/fl Cγ1Cre/+ mice after immunization, suggesting the impaired GC structure...
2018: Frontiers in Immunology
Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Xin Huang, Yingkai Li, Huiyu Feng, Pei Chen, Weibin Liu
Objectives: To describe the clinical profile, clinical outcomes and factors that may affect the outcome of juvenile myasthenia gravis (JMG) patients in southern China. Methods: We reviewed information relating to JMG patients treated and evaluated at the First Affiliated Hospital, Sun Yat-sen University, between 1998 and 2015. The study involved 327 JMG patients who had been followed up for ≥1 year. Results: Overall, 77.4% patients showed initial symptoms in the prepubertal period (<12 years)...
2018: Frontiers in Neurology
Conglei Li, Thergiory Irrazabal, Clare C So, Maribel Berru, Likun Du, Evelyn Lam, Alexanda K Ling, Jennifer L Gommerman, Qiang Pan-Hammarström, Alberto Martin
Class switch recombination (CSR) has a fundamental function during humoral immune response and involves the induction and subsequent repair of DNA breaks in the immunoglobulin (Ig) switch regions. Here we show the role of Usp22, the SAGA complex deubiquitinase that removes ubiquitin from H2B-K120, in the repair of programmed DNA breaks in vivo. Ablation of Usp22 in primary B cells results in defects in γH2AX and impairs the classical non-homologous end joining (c-NHEJ), affecting both V(D)J recombination and CSR...
March 8, 2018: Nature Communications
Alisa Dewan, Mengtan Xing, Marie Benner Lundbæk, Raquel Gago-Fuentes, Carole Beck, Per Arne Aas, Nina-Beate Liabakk, Siri Sæterstad, Khac Thanh Phong Chau, Bodil Merete Kavli, Valentyn Oksenych
To ensure genome stability, mammalian cells employ several DNA repair pathways. Nonhomologous DNA end joining (NHEJ) is the DNA repair process that fixes double-strand breaks throughout the cell cycle. NHEJ is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (CSR). NHEJ consists of several core and accessory factors, including Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, Artemis, and XLF. Paralog of XRCC4 and XLF (PAXX) is the recently described accessory NHEJ factor that structurally resembles XRCC4 and XLF and interacts with Ku70/Ku80...
March 2018: FEBS Open Bio
Raquel Gago-Fuentes, Mengtan Xing, Siri Sæterstad, Antonio Sarno, Alisa Dewan, Carole Beck, Stefano Bradamante, Magnar Bjørås, Valentyn Oksenych
DNA repair consists of several cellular pathways which recognize and repair damaged DNA. The classical nonhomologous DNA end-joining (NHEJ) pathway repairs double-strand breaks in DNA. It is required for maturation of both B and T lymphocytes by supporting V(D)J recombination as well as B-cell differentiation during class switch recombination (CSR). Inactivation of NHEJ factors Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, and Artemis impairs V(D)J recombination and blocks lymphocyte development. Paralogue of XRCC4 and XLF (PAXX) is an accessory NHEJ factor that has a significant impact on the repair of DNA lesions induced by ionizing radiation in human, murine, and chicken cells...
March 2018: FEBS Open Bio
Sang-Hoon Lee, Seok-Rae Park
Interaction between pathogen-associated molecular patterns and pattern recognition receptors triggers innate and adaptive immune responses. Several studies have reported that toll-like receptors (TLRs) are involved in B cell proliferation, differentiation, and Ig class switch recombination (CSR). However, roles of TLRs in B cell activation and differentiation are not completely understood. In this study, we investigated the direct effect of stimulation of TLR1/2 agonist Pam3CSK4 on mouse B cell viability, proliferation, activation, Ig production, and Ig CSR in vitro ...
February 2018: Immune Network
O K Spaans, K A Macdonald, J A S Lancaster, A M Bryant, J R Roche
Economic optimum stocking rates for grazing dairy systems have been defined by accounting for the pasture production potential of the farm [t of dry matter (DM)/ha], the amount of feed imported from outside the farm (t of DM/ha), and the size of the cow (kg). These variables were combined into the comparative stocking rate [CSR; kg of body weight (BW)/t of feed DM available] measure. However, CSR assumes no effect of cow genetics beyond BW, and there is increasing evidence of within-breed differences in residual feed intake and between-breed differences in the gross efficiency with which cows use metabolizable energy for milk production...
February 28, 2018: Journal of Dairy Science
Fatma Gargouri, Fathi Kallel, Sebastien Delphine, Ahmed Ben Hamida, Stéphane Lehéricy, Romain Valabregue
Resting state functional MRI (rs-fMRI) is an imaging technique that allows the spontaneous activity of the brain to be measured. Measures of functional connectivity highly depend on the quality of the BOLD signal data processing. In this study, our aim was to study the influence of preprocessing steps and their order of application on small-world topology and their efficiency in resting state fMRI data analysis using graph theory. We applied the most standard preprocessing steps: slice-timing, realign, smoothing, filtering, and the tCompCor method...
2018: Frontiers in Computational Neuroscience
Erich Michel, Olivier Duss, Frédéric H-T Allain
Posttranscriptional regulation of gene expression by small noncoding RNAs (sRNAs) is an important control mechanism that modulates bacterial metabolism, motility, and pathogenesis. Using the bacterial carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) system, we here describe an E. coli-based cell-free translation assay that allows a quantitative analysis of translation regulation by ncRNAs and their corresponding translation repressor proteins. The assay quantifies the translation of chloramphenicol acetyltransferase in cell-free expression reactions that contain defined amounts of ncRNA and repressor protein...
2018: Methods in Molecular Biology
Jennifer L Wood, Caixian Tang, Ashley E Franks
Understanding how biotic and abiotic factors govern the assembly of rhizosphere-microbial communities is a long-standing goal in microbial ecology. In phytoremediation research, where plants are used to remediate heavy metal-contaminated soils, a deeper understanding of rhizosphere-microbial ecology is needed to fully exploit the potential of microbial-assisted phytoremediation. This study investigated whether Grime's competitor/stress-tolerator/ruderal (CSR) theory could be used to describe the impact of cadmium (Cd) and the presence of a Cd-accumulating plant, Carpobrotus rossii (Haw...
2018: Frontiers in Microbiology
Seda Keklik, Derya Gultekin-Karakas
BACKGROUND: Transnational tobacco companies (TTCs) penetrated the Turkish cigarette market due to trade and investment liberalization in the post-1980 period and eventually secured full control. Despite tobacco control policies put in place in reaction to accelerating consumption, TTCs reinforced their market power through a variety of strategies. This paper explores industry strategies that counteract tobacco control policies in Turkey. METHODS: The study employs both qualitative and quantitative analyses to explore industry strategies in Turkey...
February 26, 2018: BMC Public Health
Laurel Raffington, John Prindle, Attila Keresztes, Julia Binder, Christine Heim, Yee Lee Shing
Lower socioeconomic status (SES) environments are marked by higher stress that is hypothesized to alter cortisol secretion in children, thereby damaging hippocampal volume and memory performance. However, empirical evidence demonstrating these putative links is lacking. We assessed the diurnal cortisol awakening response (CAR) on two mornings and cortisol stress reactivity (CSR) with the Trier Social Stress Test for Children in 102 healthy, socio-demographically diverse 6-to-7-year-old children (46% female)...
February 7, 2018: Psychoneuroendocrinology
Micah Landon-Lane
This paper explores the governance characteristics of marine plastic debris, some of the factors underpinning its severity, and examines the possibility of harnessing corporate social responsibility (CSR) to manage plastic use within the contextual attitudes of a contemporary global society. It argues that international and domestic law alone are insufficient to resolve the "wicked problem" of marine plastic debris, and investigates the potential of the private sector, through the philosophy of CSR, to assist in reducing the amount and impacts of marine plastic debris...
February 2018: Marine Pollution Bulletin
Alexanda K Ling, Clare C So, Michael X Le, Audrey Y Chen, Lisa Hung, Alberto Martin
Activation-induced cytidine deaminase (AID) inflicts DNA damage at Ig genes to initiate class switch recombination (CSR) and chromosomal translocations. However, the DNA lesions formed during these processes retain an element of randomness, and thus knowledge of the relationship between specific DNA lesions and AID-mediated processes remains incomplete. To identify necessary and sufficient DNA lesions in CSR, the Cas9 endonuclease and nickase variants were used to program DNA lesions at a greater degree of predictability than is achievable with conventional induction of CSR...
February 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mukesh Dube, Ajoy Sodani, Dinesh Chouksey
PURPOSE: Myasthenia gravis (MG) is treated with many disease modifying therapies, namely corticosteroids, thymectomy and immunosuppressants, alone or in various combinations. But still, till today no consensus over the optimum therapy for MG has been made. METHODS: Out of total 101 patients with MG, 37 patients fulfilled the inclusion criteria and in them we ambispectively studied factors affecting the outcome in MG treated, to induce leukopenia, with prednisolone (PSL) plus azathioprine(AZA), from January 1993 through July 2014...
September 15, 2017: Acta Neurologica Taiwanica
En-Zhi Shen, Hao Chen, Ahmet R Ozturk, Shikui Tu, Masaki Shirayama, Wen Tang, Yue-He Ding, Si-Yuan Dai, Zhiping Weng, Craig C Mello
piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting...
February 10, 2018: Cell
Ali Noorafshan, Fatemeh Karimi, Ali-Mohammad Kamali, Saied Karbalay-Doust, Mohammad Nami
BACKGROUND AND OBJECTIVE: This study evaluated the effect of chronic sleep restriction (CSR) with or without curcumin (CUR) treatment on dendritic lengths and spines of the CA1 hippocampus using the virtual space-ball method. MATERIALS AND METHODS: Male rats were randomly submitted to nine groups, including distilled water, CUR (100 mg/kg/day), olive oil, CSR plus distilled water, CSR plus CUR, CSR plus olive oil, grid-floor plus distilled water, grid-floor plus CUR, and grid-floor plus olive oil groups...
February 15, 2018: Life Sciences
Maria C Ow, Kirill Borziak, Alexandra M Nichitean, Steve Dorus, Sarah E Hall
Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown...
February 15, 2018: PLoS Genetics
Lars Kayser, Astrid Karnoe, Dorthe Furstrand, Roy Batterham, Karl Bang Christensen, Gerald Elsworth, Richard H Osborne
BACKGROUND: For people to be able to access, understand, and benefit from the increasing digitalization of health services, it is critical that services are provided in a way that meets the user's needs, resources, and competence. OBJECTIVE: The objective of the study was to develop a questionnaire that captures the 7-dimensional eHealth Literacy Framework (eHLF). METHODS: Draft items were created in parallel in English and Danish. The items were generated from 450 statements collected during the conceptual development of eHLF...
February 12, 2018: Journal of Medical Internet Research
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