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71.
72.
Birgitta Lindqvist Bianca B. Jütte Luca Love Wlaa Assi Julie Roux Anders Snnerborg Tugsan Tezil Eric Verdin J. Peter Svensson 《PLoS pathogens》2022,18(6)
The reservoir of latently HIV-1 infected cells is heterogeneous. To achieve an HIV-1 cure, the reservoir of activatable proviruses must be eliminated while permanently silenced proviruses may be tolerated. We have developed a method to assess the proviral nuclear microenvironment in single cells. In latently HIV-1 infected cells, a zinc finger protein tethered to the HIV-1 promoter produced a fluorescent signal as a protein of interest came in its proximity, such as the viral transactivator Tat when recruited to the nascent RNA. Tat is essential for viral replication. In these cells we assessed the proviral activation and chromatin composition. By linking Tat recruitment to proviral activity, we dissected the mechanisms of HIV-1 latency reversal and the consequences of HIV-1 production. A pulse of promoter-associated Tat was identified that contrasted to the continuous production of viral proteins. As expected, promoter H3K4me3 led to substantial expression of the provirus following T cell stimulation. However, the activation-induced cell cycle arrest and death led to a surviving cell fraction with proviruses encapsulated in repressive chromatin. Further, this cellular model was used to reveal mechanisms of action of small molecules. In a proof-of-concept study we determined the effect of modifying enhancer chromatin on HIV-1 latency reversal. Only proviruses resembling active enhancers, associated with H3K4me1 and H3K27ac and subsequentially recognized by BRD4, efficiently recruited Tat upon cell stimulation. Tat-independent HIV-1 latency reversal of unknown significance still occurred. We present a method for single cell assessment of the microenvironment of the latent HIV-1 proviruses, used here to reveal how T cell stimulation modulates the proviral activity and how the subsequent fate of the infected cell depends on the chromatin context. 相似文献
73.
Torbern Tagesson Meelis Mölder Mikhail Mastepanov Charlotte Sigsgaard Mikkel P. Tamstorf Magnus Lund Julie M. Falk Anders Lindroth Torben R. Christensen Lena Ström 《Global Change Biology》2012,18(6):1928-1940
The land‐atmosphere exchange of methane (CH4) and carbon dioxide (CO2) in a high‐Arctic wet tundra ecosystem (Rylekærene) in Zackenberg, north‐eastern Greenland, was studied over the full growing season and until early winter in 2008 and from before snow melt until early winter in 2009. The eddy covariance technique was used to estimate CO2 fluxes and a combination of the gradient and eddy covariance methods was used to estimate CH4 fluxes. Small CH4 bursts were observed during spring thawing 2009, but these existed during short periods and would not have any significant effect on the annual budget. Growing season CH4 fluxes were well correlated with soil temperature, gross primary production, and active layer thickness. The CH4 fluxes remained low during the entire autumn, and until early winter. No increase in CH4 fluxes were seen as the soil started to freeze. However, in autumn 2008 there were two CH4 burst events that were highly correlated with atmospheric turbulence. They were likely associated with the release of stored CH4 from soil and vegetation cavities. Over the measurement period, 7.6 and 6.5 g C m?2 was emitted as CH4 in 2008 and in 2009, respectively. Rylekærene acted as a C source during the warmer and wetter measurement period 2008, whereas it was a C sink for the colder and drier period of 2009. Wet tundra ecosystems, such as Rylekærene may thus play a more significant role for the climate in the future, as temperature and precipitation are predicted to increase in the high‐Arctic. 相似文献
74.
Human pluripotent stem cells (hPSCs) have shown the ability to self-organize into different types of neural organoids (e.g., whole brain organoids, cortical spheroids, midbrain organoids etc.) recently. The extrinsic and intrinsic signaling elicited by Wnt pathway, Hippo/Yes-associated protein (YAP) pathway, and extracellular microenvironment plays a critical role in brain tissue morphogenesis. This article highlights recent advances in neural tissue patterning from hPSCs, in particular the role of Wnt pathway and YAP activity in this process. Understanding the Wnt-YAP interactions should provide us the guidance to predict and modulate brain-like tissue structure through the regulation of extracellular microenvironment of hPSCs. 相似文献
75.
Yuasa HJ Hasegawa T Nakamura T Suzuki T 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,146(4):461-469
The indoleamine 2,3-dioxygenase (IDO)-like myoglobin (Mb) is a unique type of Mb isolated from the buccal mass of several archgastropod species. Here, we expressed Sulculus diversicolor IDO-like Mb as a GST-fusion protein in bacteria. The visible spectrum of GST-fusion IDO-like Mb shows characteristic α- and β-peaks, indicating that it binds oxygen. To identify residues important in heme and oxygen binding, we constructed site-directed mutants. We initially replaced each of the 7 histidines of S. diversicolor IDO-like Mb with alanine. The spectra of three mutants (H74A, H288A, and H332A) revealed a remarkable loss of absorbance around 414 nm, indicating that they cannot bind heme. His74, His288, and His332 were also replaced by arginine or tyrosine. Neither H332R nor H332Y contains heme, suggesting that His332 is the proximal ligand of IDO-like Mb. In contrast, both H74R and H288Y mutants were isolated in the heme-binding oxy-form. The autoxidation rates of these two mutants showed that they can bind oxygen as stably as wild-type. His74 and His288 might be partially associated with heme-binding, but do not act as the distal ligand. The S. diversicolor IDO-like Mb seems to stably bind oxygen in a different manner from normal myoglobins. 相似文献
76.
Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase 总被引:1,自引:0,他引:1
Tintignac LA Lagirand J Batonnet S Sirri V Leibovitch MP Leibovitch SA 《The Journal of biological chemistry》2005,280(4):2847-2856
77.
78.
Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein. 总被引:9,自引:0,他引:9 下载免费PDF全文
79.
80.
Julie Thomas Saiprasad G. Palusa Giridara‐Kumar Surabhi Asa Ben‐Hur Salah E. Abdel‐Ghany Anireddy S.N. Reddy 《The Plant journal : for cell and molecular biology》2012,72(6):935-946
In Arabidopsis, pre‐mRNAs of serine/arginine‐rich (SR) proteins undergo extensive alternative splicing (AS). However, little is known about the cis‐elements and trans‐acting proteins involved in regulating AS. Using a splicing reporter (GFP–intron–GFP), consisting of the GFP coding sequence interrupted by an alternatively spliced intron of SCL33, we investigated whether cis‐elements within this intron are sufficient for AS, and which SR proteins are necessary for regulated AS. Expression of the splicing reporter in protoplasts faithfully produced all splice variants from the intron, suggesting that cis‐elements required for AS reside within the intron. To determine which SR proteins are responsible for AS, the splicing pattern of the GFP–intron–GFP reporter was investigated in protoplasts of three single and three double mutants of SR genes. These analyses revealed that SCL33 and a closely related paralog, SCL30a, are functionally redundant in generating specific splice variants from this intron. Furthermore, SCL33 protein bound to a conserved sequence in this intron, indicating auto‐regulation of AS. Mutations in four GAAG repeats within the conserved region impaired generation of the same splice variants that are affected in the scl33 scl30a double mutant. In conclusion, we have identified the first intronic cis‐element involved in AS of a plant SR gene, and elucidated a mechanism for auto‐regulation of AS of this intron. 相似文献