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Fernando Grigera, Robert Wuerffel, Amy L Kenter
Immunoglobulin heavy chain class switch recombination (CSR) requires targeted formation of DNA double strand breaks (DSBs) in repetitive switch region elements followed by ligation between distal breaks. The introduction of DSBs is initiated by activation induced cytidine deaminase (AID) and requires base excision repair (BER) and mismatch repair (MMR). The BER enzyme, methyl CpG binding domain protein 4 (MBD4) has been linked to the MMR pathway through its interaction with MutL homologue 1 (MLH1). We find that when the Mbd4 exons 6-8 are deleted in a switching B cell line DSB formation is severely reduced and CSR frequency is impaired...
October 24, 2016: Molecular and Cellular Biology
Cuixia Gao, Bingxian Yang, Dandan Zhang, Meng Chen, Jingkui Tian
BACKGROUND: Indole alkaloids, which characteristically contain an indole nucleus, have pharmaceutical potential in a diverse range of applications. UV-B can elicit the accumulation of indole alkaloids. The indole alkaloid (6-hydroxyl-1H-indol-3-yl) carboxylic acid methyl ester with cytotoxic activity was found to accumulate in Clematis terniflora DC. leaves after exposure to high level of UV-B irradiation and the dark. However, a more in-depth analysis of the process behind this response has not yet been performed...
October 24, 2016: BMC Plant Biology
Yongcheng Pan, Lusi Zhang, Qiong Liu, Ying Li, Hui Guo, Yu Peng, Hexiang Peng, Beisha Tang, Zhengmao Hu, Jingping Zhao, Kun Xia, Jia-Da Li
AMPD1 is an adenosine monophosphate deaminase that catalyzes the deamination of AMP to IMP. To understand the physiological function of AMPD1, we obtained a strain of Ampd1 mutant mice from KOMP repository, which was generated by a knockout-first strategy. An elevated AMP level and almost complete lack of IMP was detected in the skeletal muscle of E18.5 Ampd1(tm1a/tm1a) mice. However, Ampd1(tm1a/tm1a) mice died in 2 days postnatally, which was contradicting to previous reports. After removal of the knockout-first cassette and critical exon, mice homozygous for the Ampd1(tm1c/tm1c) and Ampd1(tm1d/tm1d) alleles survived to adulthood...
October 24, 2016: Scientific Reports
Amy E DeZern, Amer M Zeidan, John Barnard, Wesley Hand, Najla Al Ali, Francis Brown, Cassie Zimmerman, Gail J Roboz, Guillermo Garcia-Manero, David P Steensma, Rami S Komrokji, Mikkael A Sekeres
First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex...
October 24, 2016: Leukemia & Lymphoma
Chandrashekhar Patil, Rahul Suryawanshi, Sunil Koli, Satish Patil
Aminocyclopropane-1-carboxylate deaminase (ACCD) producing microorganisms support plant growth under a variety of biotic and abiotic stress conditions such as drought, soil salinity, flooding, heavy metal pollution and phyto-pathogen attack. Available screening methods for ACCD give idea only about its primary microbial ACCD activity than the actual potential. In the present investigation, we have simply improved screening method by incorporating pH indicator dyes (phenol red and bromothymol blue) in ACC containing medium...
October 18, 2016: Journal of Microbiological Methods
Vahid Davoudi, Kiandokht Keyhanian, Riley M Bove, Tanuja Chitnis
Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Pushpa Raj Joshi, Thekla Apitz, Stephan Zierz
During physical activity in McArdle patients, little or no lactate is released in the skeletal muscle. However, excessive ammonia production has frequently been reported in these patients. Production of ammonia is catalysed by AMP deaminase (AMPD) and adenylate kinase (AK). The activities of AMPD and AK along with housekeeping enzyme phosphoglucoisomerase (PGI) were measured in 11 genetically confirmed McArdle patients and compared with 27 healthy controls. The AMPD and AK activities were not significantly different in patients and controls...
October 20, 2016: Neurological Research
Lucas J Albano, Sheila M Macfie
A typical plant response to any biotic or abiotic stress, including cadmium (Cd), involves increased ethylene synthesis, which causes senescence of the affected plant part. Stressed plants can experience reduced ethylene and improved growth if they are inoculated with bacteria that have the enzyme ACC deaminase, which metabolizes the ethylene precursor ACC (1-aminocyclopropane-1-carboxylate). We investigated whether one such bacterium, Pseudomonas fluorescens UW4, reduces the production of ethylene and improves the growth of lettuce (Lactuca sativa) sown in Cd-contaminated potting material (PRO-MIX® BX)...
July 22, 2016: Canadian Journal of Microbiology
Biswajit Biswas, Sudershan Kumar Sharma, Rameshwar Singh Negi, Neelam Gupta, Virender Mohan Singh Jaswal, Narsimhalu Niranjan
OBJECTIVE: The present study is designed to evaluate the role of pleural fluid analysis in diagnosing pleural diseases and to study the advantages and disadvantages of thoracocentasis and pleural biopsy. MATERIALS AND METHODS: We prospectively included 66 consecutive indoor patients over a duration of 1 year. Pleural fluid was collected and cytological smears were made from the fluid. Plural biopsy was done in the same patient by Cope needle. Adequate pleural biopsy tissue yielding specific diagnosis was obtained in 47 (71...
July 2016: Journal of Cytology
Marina Cavazzana, Jean-Antoine Ribeil, Chantal Lagresle-Peyrou, Isabelle André-Schmutz
When considering inherited diseases that can be treated by gene transfer into Hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and ALD. In all other settings (X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency, Wiskott-Aldrich syndrome and β-hemoglobinopathies), the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics...
October 17, 2016: Stem Cells and Development
Sheldon Greer, Tieran Han, Cristina Dieguez, Nicola McLean, Rafael Saer, Isildinha Reis, Joe Levi, Victor E Marquez
Enzymatic activity from tumor and adjacent normal tissue of 200 patients involving deoxycytidine kinase (dCK), uridine/cytidine kinase (U/CK), cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD) was quantified. . Patients with brain (17), colon (24), and breast (30) tumors, 53, 67, and 73%, respectively, had an elevated T/N value (Specific Activity of tumor/ Specific Activity of normal tissue) involving dCK and dCMPD suggesting chemo therapy with 5-fluorodeoxycytidine (5-FdC) alone or in combination with thymidine plus deoxytetrahydrouridine, or with the radiosensitizer, 5-chlorodeoxycytidine (5-CldC) plus tetrahydrouridine (H4U)...
October 13, 2016: Anti-cancer Agents in Medicinal Chemistry
Wenjin Liu, Jeff M Snell, William R Jeck, Katherine A Hoadley, Matthew D Wilkerson, Joel S Parker, Nirali Patel, Yohannie B Mlombe, Gift Mulima, N George Liomba, Lindsey L Wolf, Carol G Shores, Satish Gopal, Norman E Sharpless
Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens...
October 6, 2016: JCI Insight
Cristina J Wittkopp, Madison B Adolph, Lily I Wu, Linda Chelico, Michael Emerman
Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution...
October 2016: PLoS Pathogens
Emily K Law, Anieta M Sieuwerts, Kelly LaPara, Brandon Leonard, Gabriel J Starrett, Amy M Molan, Nuri A Temiz, Rachel Isaksson Vogel, Marion E Meijer-van Gelder, Fred C G J Sweep, Paul N Span, John A Foekens, John W M Martens, Douglas Yee, Reuben S Harris
Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail...
October 2016: Science Advances
Lemin Li, Guanghui Qian, Yibo Zuo, Yukang Yuan, Qiao Cheng, Tingting Guo, Jin Liu, Chang Liu, Liting Zhang, Hui Zheng
Adenosine deaminase acting on RNA 1 (ADAR1) catalyzes RNA editing of cellular and viral RNAs. Besides RNA editing, ADAR1 has recently been shown to play important roles in maintaining the body balance including tissue homoeostasis, organ development and autoimmune regulations, by inhibiting both IFN production and subsequent IFN activated pathways. Accordingly, the question was raised how IFN signaling induced by viral infections overcomes the inhibitory effect of constitutively expressed ADAR1 (ADAR1-P110) to execute efficient antiviral activity...
October 11, 2016: Journal of Biological Chemistry
Tirthankar Roy, Kallol Bhattacharjee, Dwijen Das, A K Kalwar
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
A N Aggarwal, R Agarwal, I S Sehgal, S Dhooria, D Behera
OBJECTIVE: To determine the diagnostic accuracy of pleural fluid adenosine deaminase (ADA) in diagnosing tuberculous pleural effusion (TPE) among Indian patients using systematic review and meta-analysis. DESIGN: The PubMed, Embase, IndMED and Cochrane databases and other relevant publications were searched to identify Indian studies evaluating the sensitivity and specificity of ADA in diagnosing TPE. Pooled diagnostic accuracy measures and 95% confidence intervals (95%CI) were generated using a bivariate random-effects model, and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves...
October 2016: International Journal of Tuberculosis and Lung Disease
Yunqing Ma, Jiayuan Zhang, Weijie Yin, Zhenchao Zhang, Yan Song, Xing Chang
A large number of genetic variants have been associated with human diseases. However, the lack of a genetic diversification approach has impeded our ability to interrogate functions of genetic variants in mammalian cells. Current screening methods can only be used to disrupt a gene or alter its expression. Here we report the fusion of activation-induced cytidine deaminase (AID) with nuclease-inactive clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (dCas9) for efficient genetic diversification, which enabled high-throughput screening of functional variants...
October 10, 2016: Nature Methods
Ravendra Garg, Michael Theaker, Elisa C Martinez, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice...
October 6, 2016: Virology
Miriam Kaltenbach, Stephane Emond, Florian Hollfelder, Nobuhiko Tokuriki
The extent to which an emerging new function trades off with the original function is a key characteristic of the dynamics of enzyme evolution. Various cases of laboratory evolution have unveiled a characteristic trend; a large increase in a new, promiscuous activity is often accompanied by only a mild reduction of the native, original activity. A model that associates weak trade-offs with "evolvability" was put forward, which proposed that enzymes possess mutational robustness in the native activity and plasticity in promiscuous activities...
October 2016: PLoS Genetics
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