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排序方式: 共有110条查询结果,搜索用时 15 毫秒
81.
82.
Robert D. Murphy Tiantian Chen Jianping Lin Rongjun He Li Wu Caden R. Pearson Savita Sharma Carl D. Vander Kooi Anthony P. Sinai Zhong-Yin Zhang Craig W. Vander Kooi Matthew S. Gentry 《The Journal of biological chemistry》2022,298(7)
Toxoplasma gondii is an intracellular parasite that generates amylopectin granules (AGs), a polysaccharide associated with bradyzoites that define chronic T. gondii infection. AGs are postulated to act as an essential energy storage molecule that enable bradyzoite persistence, transmission, and reactivation. Importantly, reactivation can result in the life-threatening symptoms of toxoplasmosis. T. gondii encodes glucan dikinase and glucan phosphatase enzymes that are homologous to the plant and animal enzymes involved in reversible glucan phosphorylation and which are required for efficient polysaccharide degradation and utilization. However, the structural determinants that regulate reversible glucan phosphorylation in T. gondii are unclear. Herein, we define key functional aspects of the T. gondii glucan phosphatase TgLaforin (TGME49_205290). We demonstrate that TgLaforin possesses an atypical split carbohydrate-binding-module domain. AlphaFold2 modeling combined with hydrogen–deuterium exchange mass spectrometry and differential scanning fluorimetry also demonstrate the unique structural dynamics of TgLaforin with regard to glucan binding. Moreover, we show that TgLaforin forms a dual specificity phosphatase domain–mediated dimer. Finally, the distinct properties of the glucan phosphatase catalytic domain were exploited to identify a small molecule inhibitor of TgLaforin catalytic activity. Together, these studies define a distinct mechanism of TgLaforin activity, opening up a new avenue of T. gondii bradyzoite biology as a therapeutic target. 相似文献
83.
Conditional Access Agreements could improve replicability of research and enhance Open Science without jeopardizing intellectual property rights. Subject Categories: Economics, Law & Politics, Science Policy & PublishingReplicability is a cornerstone of the scientific enterprise. Validating published scientific findings enhances their credibility and helps to build a self‐correcting cumulative knowledge base. It also increases public trust in science (Wingen et al 2020). Unfortunately, the scientific community has been facing a considerable problem for at least two decades: the replication crisis (Ioannidis, 2005). Scientists in various disciplines have significant difficulties trying to verify published scientific findings (Baker, 2016). One prominent factor accounting for non‐replicability is diminished access to research materials required for replication (replication materials).
Scientists in various disciplines have significant difficulties trying to verify published scientific findings.This problem is particularly noticeable in computational studies: research that utilizes computational models, often with an immense amount of data. With the rise of powerful computers, machine learning and big data, computational studies are increasingly used in a variety of disciplines. This trend is evident in biology as well, including in systems biology, genomics, proteomics, and other areas (Markowetz, 2017). A famous example that demonstrates the importance of computational biology is the Human Genome Project. Developments in computational biology are crucial in advancing promising research prospects in areas such as vaccine antigen design and structural bioinformatics.
The problem of diminished access to replication materials has been reported as a major stumbling block impeding the replicability of computational biology studies.A scientific paper alone would not typically enable others to replicate the study described therein (Merali, 2010). Replicating a computational study generally requires access to the code, software documentation, datasets, workflows, and other information regarding the methodology (Easterbrook, 2014). In most cases, however, authors do not publicly share these elements, which renders such studies impossible to replicate (Merali, 2010; Stodden et al, 2018). The problem of diminished access to replication materials has been reported as a major stumbling block impeding the replicability of computational biology studies (Crook et al, 2013; Miłkowski et al, 2018). 相似文献
84.
85.
Lysine is catabolized via the saccharopine pathway in plants and mammals. In this pathway, lysine is converted to α-aminoadipic-δ-semialdehyde (AASA) by lysine-ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH); thereafter, AASA is converted to aminoadipic acid (AAA) by α-aminoadipic-δ-semialdehyde dehydrogenase (AASADH). Here, we investigate the occurrence, genomic organization and functional role of lysine catabolic pathways among prokaryotes. Surprisingly, only 27 species of the 1478 analyzed contain the lkr and sdh genes, whereas 323 species contain aasadh orthologs. A sdh-related gene, identified in 159 organisms, was frequently found contiguously to an aasadh gene. This gene, annotated as lysine dehydrogenase (lysdh), encodes LYSDH an enzyme that directly converts lysine to AASA. Pipecolate oxidase (PIPOX) and lysine-6-aminotransferase (LAT), that converts lysine to AASA, were also found associated with aasadh. Interestingly, many lysdh–aasadh–containing organisms live under hyperosmotic stress. To test the role of the lysine-to-AASA pathways in the bacterial stress response, we subjected Silicibacter pomeroyi to salt stress. All but lkr, sdh, lysdh and aasadh were upregulated under salt stress conditions. In addition, lysine-supplemented culture medium increased the growth rate of S. pomeroyi under high-salt conditions and induced high-level expression of the lysdh–aasadh operon. Finally, transformation of Escherichia coli with the S. pomeroyi lysdh–aasadh operon resulted in increased salt tolerance. The transformed E. coli accumulated high levels of the compatible solute pipecolate, which may account for the salt resistance. These findings suggest that the lysine-to-AASA pathways identified in this work may have a broad evolutionary importance in osmotic stress resistance. 相似文献
86.
Phylogenetic analysis of slippage-like sequence variation in the V4 rRNA expansion segment in tiger beetles (Cicindelidae) 总被引:1,自引:1,他引:0
Sequence variation in the middle part of the small-subunit rRNA was studied
for representatives of the major groups in the family Cicindelidae
(Coleoptera). All taxa exhibited a much expanded segment in variable region
V4 compared to D. melanogaster. This expanded segment was not found in
other groups of beetles, including three taxa in the closely related
Carabidae. Secondary structure predictions indicate that the expanded
segment folds into a single stem-loop structure in all taxa. Despite its
structural conservation, the fragment differs strongly in primary sequence,
even between closely related sister taxa. Several features of these
sequences are consistent with slippage replication as the mechanism that
has generated this sequence variation: the level of internal sequence
repetition as measured by the relative simplicity factor (RSF), its
variation in length between close relatives, and the strong nucleotide bias
compared to the remainder of the gene. With few exceptions, there was also
a correlation between sequence length and the level of sequence repetition,
frequently interpreted as the result of slippage. Phylogenies inferred from
the expansion segment were not consistent with existing hypotheses from
other molecular data for the group. This indicates that DNA sequences in
this region are not homologous throughout the entire Cicindelidae, but it
leaves open the possibility that this expansion segment can be used for
phylogeny reconstruction within subgroups. The implications of a
phylogenetic approach to the understanding of slippage-like evolution are
discussed.
相似文献
87.
88.
Bruges G Borges A Sánchez de Villarroel S Lippo de Bécemberg I Francis de Toba G Pláceres F González de Alfonzo R Alfonzo MJ 《Journal of receptor and signal transduction research》2007,27(2-3):189-216
Muscarinic activation of tracheal smooth muscle (TSM) involves a M(3)AChR/heterotrimeric-G protein/NPR-GC coupling mechanism. G protein activators Mastoparan (MAS) and Mastoparan-7 stimulated 4- and 10-fold the NPR-GC respectively, being insensitive to PTX and antibodies against Galpha(i/o) subfamily. Muscarinic and MAS stimulation of NPR-GC was blocked by antibodies against C-terminal of Galpha(q16), whose expression was confirmed by RT-PCR. However, synthetic peptides from C-terminal of Galpha(q15/16) stimulated the NPR-GC. Coupling of alpha(q16) to M(3)AChR is supported by MAS decreased [(3)H]QNB binding, being abolished after M(3)AChR-4-DAMP-alkylation. Anti-i(3)M(3)AChR antibodies blocked the muscarinic activation of NPR-GC, and synthetic peptide from i(3)M(3)AChR (M(3)P) was more potent than MAS increasing GTPgamma [(35)S] and decreasing the [(3)H]QNB activities. Coupling between NPR-GC and Galpha(q16) was evaluated by using trypsin-solubilized-fraction from TSM membranes, which displayed a MAS-sensitive-NPR-GC activity, being immunoprecipitated with anti-Galpha(q16), also showing an immunoreactive heterotrimeric-G-beta-subunit. These data support the existence of a novel transducing cascade, involving Galpha(q16)beta gamma coupling M(3)AChR to NPR-GC. 相似文献
89.
Sinai P Berg RE Haynie JM Egorin MJ Ilaria RL Forman J 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(4):2028-2037
Imatinib mesylate (IM) is effective at inducing complete cytogenetic remission in patients with chronic myelogenous leukemia. Because its influence on CD8 T cell responsiveness in vivo is unknown, we investigated the effects of IM by analyzing the response of OT-1 CD8 T cells to Listeria monocytogenes (LM) that express the cognate epitope OVA(257-264) (LM-OVA). In vitro, IM had no effect on Ag-specific expansion, cell division, cell cycle progression, or IFN-gamma expression in naive or memory OT-1 T cells. However, IM induced apoptosis of naive and memory OT-1 T cells at doses of >5 microM. At 15 microM IM, OT-1 T cells did not survive in in vitro cultures. The primary response of OT-1 T cells in vivo to LM-OVA infection was unaltered. In contrast, continuous IM treatment resulted in a diminished memory OT-1 response. The expression of IL-7Ralpha, a receptor required for memory cell survival, was lower (on OT-1 cells) in animals receiving IM. These results indicate that IM treatment affects the ability of the CD8 memory pool to respond to Ag and has the potential to increase susceptibility to infection. 相似文献
90.
Nimmy Mohan Sudheesh AP Nimmy Francis Richard Anderson Rakesh S. Laishram 《Nucleic acids research》2015,43(14):7005-7020
Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing. 相似文献