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Found 34081 matches. Displaying 1-10
Wu HW, Deng SL, Xu HY, Mao HZ, Liu J, Niu QW, Wang H, Chua NH
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A noncoding RNA transcribed from the AGAMOUS (AG) second intron binds to CURLY LEAF and represses AG expression in leaves

NEW PHYTOLOGIST 2018 SEP; 219(4):1480-1491
Dispersed H3K27 trimethylation (H3K27me3) of the AGAMOUS (AG) genomic locus is mediated by CURLY LEAF (CLF), a component of the Polycomb Repressive Complex (PRC) 2. Previous reports have shown that the AG second intron, which confers AG tissue-specific expression, harbors sequences targeted by several positive and negative regulators. Using RACE reverse transcription polymerase chain reaction, we found that the AG intron 2 encodes several noncoding RNAs. RNAi experiment showed that incRNA4 is needed for CLF repressive activity. AG-incRNA4RNAi lines showed increased leaf AGmRNA levels associated with a decrease of H3K27me3 levels; these plants displayed AG overexpression phenotypes. Genetic and biochemical analyses demonstrated that the AG-incRNA4 can associate with CLF to repress AG expression in leaf tissues through H3K27me3-mediated repression and to autoregulate its own expression level. The mechanism of AG-incRNA4-mediated repression may be relevant to investigations on tissue-specific expression of Arabidopsis MADS-box genes.
Galea S, Vaughan RD
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Making the Invisible Causes of Population Health Visible: A Public Health of Consequence, August 2018

Li J, Guo A, Wang QY, Li YY, Zhao J, Lu J, Pei G
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NF-kappa B directly regulates -arrestin-1 expression and forms a negative feedback circuit in TNF-alpha-induced cell death

FASEB JOURNAL 2018 AUG; 32(8):4096-4106
beta-Arrestins (beta-arrestin-1 and -2) are multifunctional proteins that play important roles in the regulation of inflammation and cell survival that need to be tightly controlled; however, the mechanism that underlies their gene expression is largely unclear. Here, we demonstrate that -arrestin-1 is a transcriptional target of NF-B. mRNA and protein levels of -arrestin-1 were up-regulated by NF-B inducers. Inhibition of NF-B prevented the up-regulation of -arrestin-1 mRNA, whereas activation of NF-B led to increased -arrestin-1 expression. -Arrestin-1 promoter activity was consistently enhanced upon NF-B activation as a result of the presence of a highly conserved B site. -Arrestin-1, in turn, suppressed the transcriptional activity of NF-B by interfering with the interaction between p65 and p50. -Arrestin-1-deficient mice displayed reduced TNF--induced cell death and increased expression of antiapoptotic genes. Reintroduction of -arrestin-1, but not its mutant, which is unable to interfere with the p65-p50 interaction, into -arrestin-deficient mouse embryonic fibroblasts partially restored sensitivity to TNF--induced cell death. These findings reveal NF-B and -arrestin-1 to be key components of a negative feedback circuit that is necessary to regulate cell death.Li, J., Guo, A., Wang, Q., Li, Y., Zhao, J., Lu, J., Pei, G. NF-B directly regulates beta-arrestin-1 expression and forms a negative feedback circuit in TNF-alpha-induced cell death.
Plawecki MH, Windisch KA, Wetherill L, Kosobud AEK, Dzemidzic M, Kareken DA, O'Connor SJ
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Alcohol affects the P3 component of an adaptive stop signal task ERP

ALCOHOL 2018 AUG; 70(?):1-10
Background: The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol-use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduce P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). Methods: One hundred forty-eight non-dependent moderate to heavy social drinkers, ages 21 to 27, participated in two single-blind, alcohol or placebo, counterbalanced sessions approximately 1 week apart. During each session, subjects performed an adaptive stop signal task (aSST) at 1) baseline, 2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and 3) approximately 135 min later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial, based on the subject's performance. Results: The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring "going" over "stopping", and SLOW SSD favoring "stopping" over "going". Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to the FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to the SLOW SSD group. Conclusions: The aSST is a robust and sensitive task for detecting alcohol-induced changes in inhibition behavior as measured by the P3 component in a within-subject design. Alcohol was associated with P3 component changes, which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response related AUD risk. (C) 2017 Elsevier Inc. All rights reserved.
Gleicher N, Kushnir VA, Darmon S, Albertini DF, Barad DH
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Older women using their own eggs? Issue framed with two oldest reported IVF pregnancies and a live birth

Research question: What level of IVF pregnancy success is currently possible in women of extremely advanced age? Design: This study reports on outcomes in women aged 43-51 years at the Centre for Human Reproduction, an academically affiliated private clinical fertility and research centre in New York City. Results: During the study years of 2014-2016, 16 pregnancies were established, all through day 3 transfers. Based on 'intent to treat' (cycle start). clinical pregnancy rates were 4/190 (2.1%), 5/234 (2.1%) and 7/304 (2.3%) and live birth rates were 2/190 (1.1%), 1/234 (0.43%) and 4/304 (1.3%) in 2014, 2015 and 2016, respectively. With reference to embryo transfer, clinical pregnancy rates were 4/140 (2.9%), 5/159 (3.1%) and 7/167 (4.2%) and live birth rates were 2/140 (1.4%), 1/159 (0.63%) and 4/167 (2.4%) for the same years. The results for 2016 also included what are probably the two oldest autologous IVF pregnancies ever reported in the literature. These results were obtained with patient ages, percentage of cycle cancellations and other adverse outcome parameters steadily increasing year by year. Conclusions: Female age above 42 is widely viewed as the ultimate barrier to conception with IVF. Data reported here, although small and preliminary, demonstrate that potential outcomes are better than widely perceived, while pregnancy and live birth rates remain significantly inferior to donor egg recipient cycles. However, for selected women at very advanced ages, especially with higher egg/embryo numbers, autologous oocyte IVF offers a better option than widely acknowledged, if they are given individualized age-specific care. (C) 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Etoc F, Balloul E, Vicario C, Normanno D, Lisse D, Sittner A, Piehler J, Dahan M, Coppey M
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Non-specific interactions govern cytosolic diffusion of nanosized objects in mammalian cells

NATURE MATERIALS 2018 AUG; 17(8):740-746
The diffusivity of macromolecules in the cytoplasm of eukaryotic cells varies over orders of magnitude and dictates the kinetics of cellular processes. However, a general description that associates the Brownian or anomalous nature of intracellular diffusion to the architectural and biochemical properties of the cytoplasm has not been achieved. Here we measure the mobility of individual fluorescent nanoparticles in living mammalian cells to obtain a comprehensive analysis of cytoplasmic diffusion. We identify a correlation between tracer size, its biochemical nature and its mobility. Inert particles with size equal or below 50 nm behave as Brownian particles diffusing in a medium of low viscosity with negligible effects of molecular crowding. Increasing the strength of non-specific interactions of the nanoparticles within the cytoplasm gradually reduces their mobility and leads to subdiffusive behaviour. These experimental observations and the transition from Brownian to subdiffusive motion can be captured in a minimal phenomenological model.
Kane M, Deiss F, Chervonsky A, Golovkina TV
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A Single Locus Controls Interferon Gamma-Independent Antiretroviral Neutralizing Antibody Responses

JOURNAL OF VIROLOGY 2018 AUG; 92(16):? Article e00725-18
An essential step in the development of effective antiviral humoral responses is cytokine-triggered class switch recombination resulting in the production of antibodies of a specific isotype. Most viral and parasitic infections in mice induce predominantly IgG2a-specific antibody responses that are stimulated by interferon gamma (IFN-gamma). However, in some mice deficient in IFN-gamma, class switching to IgG2a antibodies is relatively unaffected, indicating that another signal(s) can be generated upon viral or parasitic infections that trigger this response. Here, we found that a single recessive locus, provisionally called IFN-gamma-independent IgG2a (Igii), confers the ability to produce IFN-gamma-independent production of IgG2a antibodies upon retroviral infection. The Igii locus was mapped to chromosome 9 and was found to function in the radiation-resistant compartment. Thus, our data implicate nonhematopoietic cells in activation of antiviral antibody responses in the absence of IFN-gamma. IMPORTANCE Understanding the signals that stimulate antibody production and class switch recombination to specific antibody isotypes is crucial for the development of novel vaccines and adjuvants. While an interferon gamma-mediated switch to the IgG2a isotype upon viral infection in mice has been well established, this investigation reveals a noncanonical, interferon gamma-independent pathway for anti-retroviral antibody production and IgG2a class switch recombination that is controlled by a single recessive locus. Furthermore, this study indicates that the radiation-resistant compartment can direct antiviral antibody responses, suggesting that detection of infection by nonhematopoietic cells is involved is stimulating adaptive immunity.
Gleicher N, Kushnir VA, Barad DH
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How PGS/PGT-A laboratories succeeded in losing all credibility

Ule J, Hwang HW, Darnell RB
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The Future of Cross-Linking and Immunoprecipitation (CLIP)

To understand the assembly and functional outcomes of protein-RNA regulation, it is crucial to precisely identify the positions of such interactions. Cross-linking and immunoprecipitation (CLIP) serves this purpose by exploiting covalent protein-RNA cross-linking and RNA fragmentation, along with a series of stringent purification and quality control steps to prepare complementary DNA (cDNA) libraries for sequencing. Here we describe the core steps of CLIP, its primary variations, and the approaches to data analysis. We present the application of CLIP to studies of specific cell types in genetically engineered mice and discuss the mechanistic and physiologic insights that have already been gained from studies using CLIP. We conclude by discussing the future opportunities for CLIP, including studies of human postmortem tissues from disease patients and controls, RNA epigenetic modifications, and RNA structure. These and other applications of CLIP will continue to unravel fundamental gene regulatory mechanisms while providing important biologic and clinically relevant insights.
Hawks RM, McGinn AP, Bernstein PS, Tobin JN
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Exploring Preconception Care: Insurance Status, Race/Ethnicity, and Health in the Pre-pregnancy Period

Objective To measure the association of preconception health insurance status with preconception health among women in New York City, and examine whether this association is modified by race/ethnicity. Methods Using data from the New York City Pregnancy Risk Assessment Monitoring System 2009-2011 (n = 3929), we created a "Preconception Health Score" (PHS) capturing modifiable behaviors, healthcare services utilization, pregnancy intention, and timely entry into prenatal care. We then built multivariable logistic regression models to measure the association of PHS with health insurance status and race/ethnicity. Results We found PHS to be higher among women with private insurance (7.3 +/- 0.07) or public insurance (6.3 +/- 0.08) before pregnancy than no insurance (5.9 +/- 0.09) (p < .001). However, when stratified by race/ethnicity, the positive association of PHS with insurance was absent in the non-white population. Conclusions for Practice Having health insurance during the pre-pregnancy period is associated with greater health among white women, but not among black or Hispanic women in NYC.