Species-specific regulation of fibrinogen synthesis with implications for porcine hepatocyte xenotransplantation

2014 ◽  
Vol 21 (5) ◽  
pp. 444-453 ◽  
Author(s):  
Wolf Ramackers ◽  
Johannes Klose ◽  
Florian W. R. Vondran ◽  
Harald Schrem ◽  
Alexander Kaltenborn ◽  
...  
2021 ◽  
Vol 22 (9) ◽  
pp. 4637
Author(s):  
Daniel Barth ◽  
Andreas Lückhoff ◽  
Frank J. P. Kühn

The human apoptosis channel TRPM2 is stimulated by intracellular ADR-ribose and calcium. Recent studies show pronounced species-specific activation mechanisms. Our aim was to analyse the functional effect of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), commonly referred to as PIP2, on different TRPM2 orthologues. Moreover, we wished to identify the interaction site between TRPM2 and PIP2. We demonstrate a crucial role of PIP2, in the activation of TRPM2 orthologues of man, zebrafish, and sea anemone. Utilizing inside-out patch clamp recordings of HEK-293 cells transfected with TRPM2, differential effects of PIP2 that were dependent on the species variant became apparent. While depletion of PIP2 via polylysine uniformly caused complete inactivation of TRPM2, restoration of channel activity by artificial PIP2 differed widely. Human TRPM2 was the least sensitive species variant, making it the most susceptible one for regulation by changes in intramembranous PIP2 content. Furthermore, mutations of highly conserved positively charged amino acid residues in the membrane interfacial cavity reduced the PIP2 sensitivity in all three TRPM2 orthologues to varying degrees. We conclude that the membrane interfacial cavity acts as a uniform PIP2 binding site of TRPM2, facilitating channel activation in the presence of ADPR and Ca2+ in a species-specific manner.


2003 ◽  
Vol 278 (24) ◽  
pp. 21502-21509 ◽  
Author(s):  
Sven Heinz ◽  
Viola Haehnel ◽  
Marina Karaghiosoff ◽  
Lucia Schwarzfischer ◽  
Mathias Müller ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Michelle M. Halstead ◽  
Xin Ma ◽  
Chuan Zhou ◽  
Richard M. Schultz ◽  
Pablo J. Ross

Abstract The shift from maternal to embryonic control is a critical developmental milestone in preimplantation development. Widespread transcriptomic and epigenetic remodeling facilitate this transition from terminally differentiated gametes to totipotent blastomeres, but the identity of transcription factors (TF) and genomic elements regulating embryonic genome activation (EGA) are poorly defined. The timing of EGA is species-specific, e.g., the timing of murine and human EGA differ significantly. To deepen our understanding of mammalian EGA, here we profile changes in open chromatin during bovine preimplantation development. Before EGA, open chromatin is enriched for maternal TF binding, similar to that observed in humans and mice. During EGA, homeobox factor binding becomes more prevalent and requires embryonic transcription. A cross-species comparison of open chromatin during preimplantation development reveals strong similarity in the regulatory circuitry underlying bovine and human EGA compared to mouse. Moreover, TFs associated with murine EGA are not enriched in cattle or humans, indicating that cattle may be a more informative model for human preimplantation development than mice.


2001 ◽  
Vol 69 (4) ◽  
pp. 2502-2511 ◽  
Author(s):  
Yih-Ling Tzeng ◽  
John S. Swartley ◽  
Yoon K. Miller ◽  
Rachel E. Nisbet ◽  
Li-Jun Liu ◽  
...  

ABSTRACT The clinically important serogroups B, C, Y, and W-135 ofNeisseria meningitidis produce sialic acid capsules that are critical in pathogenesis. In each of these serogroups, the capsule transport (ctrABCD) and capsule biosynthesis (synABCD) operons are divergently transcribed from putative promoters located in a 134-bp intergenic region (J. S. Swartley, J. H. Ahn, L. J. Liu, C. M. Kahler, and D. S. Stephens, J. Bacteriol. 178:4052–4059, 1996). In this study we further assessed the role of the intergenic sequence in the transcriptional regulation of the sialic acid capsules of N. meningitidis. Insertional mutagenesis or deletions of the 134-bp sequence in the serogroup B meningococcal strain NMB resulted in a marked reduction or elimination of ctrABCD and synABCDtranscription, with a concomitant loss of encapsulation. Chromosomal transcriptional lacZ-ermC reporter fusions ofsyn and ctr promoters were constructed through allelic exchange. Using these constructs, both operons were found to be constitutively transcribed in meningococci, the biosynthesis operon about fourfold higher than the transport operon. Both promoters showed increased activity during stationary-phase growth. In addition to the promoters, a 70-bp 5′ untranslated region (UTR) upstream ofsynA was found to have a direct repeat and an inverted repeat that overlapped three putative integration host factor binding sites. Mutation of this 70-bp UTR and of the direct repeat upregulated both syn and ctr transcription. Regulation through the synA UTR was absent in a K1 Escherichia coli strain that produces identical capsular polysaccharide, implicating species-specific regulation. Meningococcal sialic acid capsule expression is initiated by divergent promoters in a 134-bp intergenic region, is repressed at the transcriptional level by the 5′ UTR of synA, is increased during stationary-phase growth, and shows species-specific regulation. Transcriptional regulation is another important control point for sialic capsule expression inN. meningitidis.


PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192746 ◽  
Author(s):  
Ruth Morgan ◽  
John Keen ◽  
Daniel Halligan ◽  
Alan O’Callaghan ◽  
Ruth Andrew ◽  
...  

1997 ◽  
Vol 272 (6) ◽  
pp. 3583-3589 ◽  
Author(s):  
Andrew P. Waters ◽  
Rosalina M. L. van Spaendonk ◽  
Jai Ramesar ◽  
Richard A. W. Vervenne ◽  
Roeland W. Dirks ◽  
...  

IUBMB Life ◽  
2005 ◽  
Vol 57 (4-5) ◽  
pp. 363-370 ◽  
Author(s):  
Virna Leaner ◽  
Agatha Masemola ◽  
Iqbal Parker

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Cheng Shi ◽  
Alexi M Runnels ◽  
Coleen T Murphy

Differences in longevity between sexes is a mysterious yet general phenomenon across great evolutionary distances. To test the roles of responses to environmental cues and sexual behaviors in longevity regulation, we examined Caenorhabditis male lifespan under solitary, grouped, and mated conditions. We find that neurons and the germline are required for male pheromone-dependent male death. Hermaphrodites with a masculinized nervous system secrete male pheromone and are susceptible to male pheromone killing. Male pheromone-mediated killing is unique to androdioecious Caenorhabditis, and may reduce the number of males in hermaphroditic populations; neither males nor females of gonochoristic species are susceptible to male pheromone killing. By contrast, mating-induced death, which is characterized by germline-dependent shrinking, glycogen loss, and ectopic vitellogenin expression, utilizes distinct molecular pathways and is shared between the sexes and across species. The study of sex- and species-specific regulation of aging reveals deeply conserved mechanisms of longevity and population structure regulation.


2014 ◽  
Vol 385 (2) ◽  
pp. 380-395 ◽  
Author(s):  
Jane Hall ◽  
Andrew H. Jheon ◽  
Erin L. Ealba ◽  
B. Frank Eames ◽  
Kristin D. Butcher ◽  
...  

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