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141.
Urban environments expose species to contrasting selection pressures relative to rural areas due to altered microclimatic conditions, habitat fragmentation, and changes in species interactions. To improve our understanding on how urbanization impacts selection through biotic interactions, we assessed differences in plant defense and tolerance, dispersal, and flowering phenology of a common plant species (Taraxacum officinale) along an urbanization gradient and their reaction norms in response to a biotic stressor (i.e., herbivory). We raised plants from 45 lines collected along an urbanization gradient under common garden conditions and assessed the impact of herbivory on plant growth (i.e., aboveground biomass), dispersal capacity (i.e., seed morphology), and plant phenology (i.e., early seed production) by exposing half of our plants to two events of herbivory (i.e., grazing by locusts). Independent from their genetic background, all plants consistently increased their resistance to herbivores by which the second exposure to locusts resulted in lower levels of damage suffered. Herbivory had consistent effects on seed pappus length, with seeds showing a longer pappus (and, hence, increased dispersal capacities) regardless of urbanization level. Aboveground plant biomass was neither affected by urbanization nor herbivore presence. In contrast to consistent responses in plant defenses and pappus length, plant fitness did vary between lines. Urban lines had a reduced early seed production following herbivory while rural and suburban lines did not show any plastic response. Our results show that herbivory affects plant phenotypes but more importantly that differences in herbivory reaction norms exist between urban and rural populations. 相似文献
142.
143.
Conidi A Cazzola S Beets K Coddens K Collart C Cornelis F Cox L Joke D Dobreva MP Dries R Esguerra C Francis A Ibrahimi A Kroes R Lesage F Maas E Moya I Pereira PN Stappers E Stryjewska A van den Berghe V Vermeire L Verstappen G Seuntjens E Umans L Zwijsen A Huylebroeck D 《Cytokine & growth factor reviews》2011,22(5-6):287-300
144.
145.
Xavier Hanoulle Aurélie Badillo Jean-Michel Wieruszeski Dries Verdegem Isabelle Landrieu Ralf Bartenschlager Fran?ois Penin Guy Lippens 《The Journal of biological chemistry》2009,284(20):13589-13601
We report here a biochemical and structural characterization of domain 2 of
the nonstructural 5A protein (NS5A) from the JFH1 Hepatitis C virus strain and
its interactions with cyclophilins A and B (CypA and CypB). Gel filtration
chromatography, circular dichroism spectroscopy, and finally NMR spectroscopy
all indicate the natively unfolded nature of this NS5A-D2 domain. Because
mutations in this domain have been linked to cyclosporin A resistance, we used
NMR spectroscopy to investigate potential interactions between NS5A-D2 and
cellular CypA and CypB. We observed a direct molecular interaction between
NS5A-D2 and both cyclophilins. The interaction surface on the cyclophilins
corresponds to their active site, whereas on NS5A-D2, it proved to be
distributed over the many proline residues of the domain. NMR heteronuclear
exchange spectroscopy yielded direct evidence that many proline residues in
NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl
cis/trans isomerase (PPIase) activity of CypA and CypB.Hepatitis C virus
(HCV)4 is a small,
positive strand, RNA-enveloped virus belonging to the Flaviviridae family and
the genus Hepacivirus. With 120–180 million chronically
infected individuals worldwide, hepatitis C virus infection represents a major
cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma
(1). The HCV viral genome
(∼9.6 kb) codes for a unique polyprotein of ∼3000 amino acids
(recently reviewed in Refs.
2–4).
Following processing via viral and cellular proteases, this polyprotein gives
rise to at least 10 viral proteins, divided into structural (core, E1, and E2
envelope glycoproteins) and nonstructural proteins (p7, NS2, NS3, NS4A, NS4B,
NS5A, NS5B). Nonstructural proteins are involved in polyprotein processing and
viral replication. The set composed of NS3, NS4A, NS4B, NS5A, and NS5B
constitutes the minimal protein component required for viral replication
(5).Cyclophilins are cellular proteins that have been identified first as
CsA-binding proteins (6). As
FK506-binding proteins (FKBP) and parvulins, cyclophilins are peptidyl-prolyl
cis/trans isomerases (PPIase) that catalyze the
cis/trans isomerization of the peptide linkage preceding a proline
(6,
7). Several subtypes of
cyclophilins are present in mammalian cells
(8). They share a high sequence
homology and a well conserved three-dimensional structure but display
significant differences in their primary cellular localization and in
abundance (9). CypA, the most
abundant of the cyclophilins, is primarily cytoplasmic, whereas CypB is
directed to the endoplasmic reticulum lumen or the secretory pathway. CypD, on
the other hand, is the mitochondrial cyclophilin. Cyclophilins are involved in
numerous physiological processes such as protein folding, immune response, and
apoptosis and also in the replication cycle of viruses including vaccinia
virus, vesicular stomatitis virus, severe acute respiratory syndrome
(SARS)-coronavirus, and human immunodeficiency virus (HIV) (for review see
Ref. 10). For HIV, CypA has
been shown to interact with the capsid domain of the HIV Gag precursor
polyprotein (11). CypA thereby
competes with capsid domain/TRIM5 interaction, resulting in a loss of the
antiviral protective effect of the cellular restriction factor TRIM5α
(12,
13). Moreover, it has been
shown that CypA catalyzes the cis/trans isomerization of
Gly221-Pro222 in the capsid domain and that it has
functional consequences for HIV replication efficiency
(14–16).
For HCV, Watashi et al.
(17) have described a
molecular and functional interaction between NS5B, the viral RNA-dependent RNA
polymerase (RdRp), and cyclophilin B (CypB). CypB may be a key regulator in
HCV replication by modulating the affinity of NS5B for RNA. This regulation is
abolished in the presence of cyclosporin A (CsA), an inhibitor of cyclophilins
(6). These results provided for
the first time a molecular mechanism for the early-on observed anti-HCV
activity of CsA
(18–20).
Although this initial report suggests that only CypB would be involved in the
HCV replication process (17),
a growing number of studies have recently pointed out a role for other
cyclophilins
(21–25).In vitro selection of CsA-resistant HCV mutants indicated the
importance of two HCV nonstructural proteins, NS5B and NS5A
(26), with a preponderant
effect for mutations in the C-terminal half of NS5A. NS5A is a large
phosphoprotein (49 kDa), indispensable for HCV replication and particle
assembly
(27–29),
but for which the exact function(s) in the HCV replication cycle remain to be
elucidated. This nonstructural protein is anchored to the cytoplasmic leaflet
of the endoplasmic reticulum membrane via an N-terminal amphipathic
α-helix (residues 1–27)
(30,
31). Its cytoplasmic sequence
can be divided into three domains: D1 (residues 27–213), D2 (residues
250–342), and D3 (residues 356–447), all connected by low
complexity sequences (32). D1,
a zinc-binding domain, adopts a dimeric claw-shaped structure, which is
proposed to interact with RNA
(33,
34). NS5A-D2 is essential for
HCV replication, whereas NS5A-D3 is a key determinant for virus infectious
particle assembly (27,
35). NS5A-D2 and -D3, for
which sequence conservation among HCV genotypes is significantly lower than
for D1, have been proposed to be natively unfolded domains
(28,
32). Molecular and structural
characterization of NS5A-D2 from HCV genotype 1a has confirmed the disordered
nature of this domain (36,
37).As it is still not clear which cyclophilins are cofactors for HCV
replication, and as mutations in HCV NS5A protein have been associated with
CsA resistance, we decided to examine the interaction between both CypA and
CypB and domain 2 of the HCV NS5A protein. We first characterized, at the
molecular level, NS5A-D2 from the HCV JFH1 infectious strain (genotype 2a) and
showed by NMR spectroscopy that this natively unfolded domain indeed interacts
with both cyclophilin A and cyclophilin B. Our NMR chemical shift mapping
experiments indicated that the interaction occurs at the level of the
cyclophilin active site, whereas it lacks a precise localization on NS5A-D2. A
peptide derived from the only well conserved amino acid motif in NS5A-D2 did
interact with cyclophilin A but only with a 10-fold lower affinity than the
full domain. We concluded from this that the many proline residues form
multiple anchoring points, especially when they adopt the cis
conformation. NMR exchange spectroscopy further demonstrated that NS5A-D2 is a
substrate for the PPIase activities of both CypA and CypB. Both the
NS5A/cyclophilin interaction and the PPIase activity of the cyclophilins on
NS5A-D2 were abolished by CsA, underscoring the specificity of the
interaction. 相似文献
146.
Iris?VillarrealEmail author Katleen?Vranckx Dries?Calus Frank?Pasmans Freddy?Haesebrouck Dominiek?Maes 《BMC veterinary research》2012,8(1):2
Background
Mycoplasma hyopneumoniae is the primary cause of enzootic pneumonia in pigs. Although vaccination is an important control tool, the results observed under field conditions are variable. This may be due to antigenic differences between the strains circulating in pig herds and the vaccine strain. This study compared the protective efficacy of four bacterins against challenge infection with a highly virulent field strain of M. hyopneumoniae. 相似文献147.
Caroline Fauquant Dries Verdegem Laziza Amniai Arnaud Leroy Jean‐Michel Wieruszeski Guy Lippens Isabelle Landrieu 《Proteins》2012,80(2):454-462
Phosphorylation of the neuronal Tau protein is implicated in both the regulation of its physiological function of microtubule stabilization and its pathological propensity to aggregate into the fibers that characterize Alzheimer's diseased neurons. However, how specific phosphorylation events influence both aspects of Tau biology remains largely unknown. In this study, we address the structural impact of phosphorylation of the Tau protein by Nuclear Magnetic Resonance (NMR) spectroscopy on a functional fragment of Tau (Tau[Ser208–Ser324] = TauF4). TauF4 was phosphorylated by the proline‐directed CDK2/CycA3 kinase on Thr231 (generating the AT180 epitope), Ser235, and equally on Thr212 and Thr217 in the Proline‐rich region (Tau[Ser208‐Gln244] or PRR). These modifications strongly decrease the capacity of TauF4 to polymerize tubulin into microtubules. While all the NMR parameters are consistent with a globally disordered Tau protein fragment, local clusters of structuration can be defined. The most salient result of our NMR analysis is that phosphorylation in the PRR stabilizes a short α‐helix that runs from pSer235 till the very beginning of the microtubule‐binding region (Tau[Thr245‐Ser324] or MTBR of TauF4). Phosphorylation of Thr231/Ser235 creates a N‐cap with helix stabilizing role while phosphorylation of Thr212/Thr217 does not induce modification of the local transient secondary structure, showing that the stabilizing effect is sequence specific. Using paramagnetic relaxation experiments, we additionally show a transient interaction between the PRR and the MTBR, observed in both TauF4 and phospho‐TauF4. Proteins 2012. © 2011 Wiley Periodicals, Inc. 相似文献
148.
Molecular mechanisms of feedback inhibition of protein kinase A on intracellular cAMP accumulation 总被引:1,自引:0,他引:1
The cAMP-protein kinase A (PKA) pathway is a major signalling pathway in the yeast Saccharomyces cerevisiae, but also in many other eukaryotic cell types, including mammalian cells. Since cAMP plays a crucial role as second messenger in the regulation of this pathway, its levels are strictly controlled, both in the basal condition and after induction by agonists. A major factor in the down-regulation of the cAMP level after stimulation is PKA itself. Activation of PKA triggers feedback down-regulation of the increased cAMP level, stimulating its return to the basal concentration. This is accomplished at different levels. The best documented mechanisms are: inhibition of cAMP synthesis by down-regulation of adenylate cyclase and/or its regulatory proteins, stimulation of cAMP breakdown by phosphodiesterases and spatial regulation of cAMP levels in the cell by A-Kinase Anchoring Proteins (AKAPs). In this review we describe these processes in detail for S. cerevisiae, for cells of mammals and selected other organisms, and we hint at other possible targets for feedback regulation of intracellular cAMP levels. 相似文献
149.
Dries Castermans Ils Somers Johan Kriel Wendy Louwet Stefaan Wera Matthias Versele Veerle Janssens Johan M Thevelein 《Cell research》2012,22(6):1058-1077
The protein phosphatases PP2A and PP1 are major regulators of a variety of cellular processes in yeast and other eukaryotes. Here, we reveal that both enzymes are direct targets of glucose sensing. Addition of glucose to glucose-deprived yeast cells triggered rapid posttranslational activation of both PP2A and PP1. Glucose activation of PP2A is controlled by regulatory subunits Rts1, Cdc55, Rrd1 and Rrd2. It is associated with rapid carboxymethylation of the catalytic subunits, which is necessary but not sufficient for activation. Glucose activation of PP1 was fully dependent on regulatory subunits Reg1 and Shp1. Absence of Gac1, Glc8, Reg2 or Red1 partially reduced activation while Pig1 and Pig2 inhibited activation. Full activation of PP2A and PP1 was also dependent on subunits classically considered to belong to the other phosphatase. PP2A activation was dependent on PP1 subunits Reg1 and Shp1 while PP1 activation was dependent on PP2A subunit Rts1. Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent. Reg1-Glc7 interaction is responsible for PP1 involvement in the main glucose repression pathway and we show that deletion of Shp1 also causes strong derepression of the invertase gene SUC2. Deletion of the PP2A subunits Pph21 and Pph22, Rrd1 and Rrd2, specifically enhanced the derepression level of SUC2, indicating that PP2A counteracts SUC2 derepression. Interestingly, the effect of the regulatory subunit Rts1 was consistent with its role as a subunit of both PP2A and PP1, affecting derepression and repression of SUC2, respectively. We also show that abolished phosphatase activation, except by reg1Δ, does not completely block Snf1 dephosphorylation after addition of glucose. Finally, we show that glucose activation of the cAMP-PKA (protein kinase A) pathway is required for glucose activation of both PP2A and PP1. Our results provide novel insight into the complex regulatory role of these two major protein phosphatases in glucose regulation. 相似文献
150.
We hypothesized that the contrasting soil conditions resulting from different historical land use in heathlands mediate the interactions of Calluna vulgaris with pollinators. We compared using a common garden experiment, the flowering phenology, the interaction with pollinators, and the colonization by ericoid mycorrhiza of mature C. vulgaris on three types of soils namely: (1) natural rhizospheric soil collected in a natural heath, (2) soil from an arable land recently restored into a heathland, and (3) soil of C. vulgaris from an area in which a high degree of heterospecific competition with perennial grasses occurred. The results of the experiment showed a strong effect of soil on flower phenology and synchrony. There was also an interaction with pollinators because not only did visitation rates depend on soil provenance but also the choice of plant by the pollinator, at least for honeybees, was affected by soil provenance. An a posteriori correlation analysis suggests that ericoid mycorrhizal fungi and not abiotic conditions across the different soil provenances may be involved in the interaction between plants and pollinators. The results obtained from this study highlight the importance of soil processes to understand plant–pollinator interactions and point at plant–soil feedbacks as an important mechanism for understanding heathland ecology. 相似文献