We investigate an inverse (
I
) dithienylethene, the bis(3,5-dimethyl-2-thienyl) perfluorocyclopentene, using absorption, emission and NMR spectroscopies as well as state-of-art first-principles ...(TDDFT) calculations. First, we find in addition to the expected antiparallel
AP1
and parallel
P2
conformers, a new stable antiparallel conformer
AP3
, but its energy is too high to be significantly populated at working temperature. More importantly, we demonstrate that, instead of an equal proportion of an AP and a P conformer as in normal (N) diarylethenes, the AP conformer is present in large excess. This result is confirmed by both DFT thermodynamical analysis and temperature-dependent NMR experiments modelized with an
AP1
↔
P2
fast interconversion model. With the latter, the relative populations are estimated to be
ca.
3/1 for
AP1
/
P2
. Furthermore, the 0-0 energies simulated with a model that accounts for both vibrational and state-specific media effects of the ground and the excited states indicate that
AP1
and
P2
have very similar absorption signatures while only the
P2
conformer should give rise to emission. Eventually, within excited state manifold, important topological points along the ring-closure reaction coordinate, and more specifically the unprecedented S1(opt) of the closed isomer, have been identified.
Inverse dithienylethenes cannot be considered as a simple generalization of normal dithienylethenes, as demonstrated in this joint experimental-theoretical study.
This work deals with the photophysics of novel pyridinium betaine based on 2-pyridin-1-yl-1
H
-benzimidazole (SBPa) substituted symmetrically by mono- (Th
2
SBPa) and bi-thiophene fragments (Th
4
...SBPa). The study is based on a combination of steady-state, femtosecond transient absorption spectroscopic measurements supported by PCM-(TD)DFT calculations. It is found that the two step ICT process (S
0
→ S
2
excitation followed by S
2
(CT) → S
1
(CT) internal conversion) occurring for the parent molecule remains unaffected for Th
2
SBPa while the situation is less clear for Th
4
SBPa. Actually, for both molecules, a new decay route involving the π-electron system localized in thiophenic groups is responsible for the production of triplet states. Involvement of this new route in the parallel production of S
1
(CT) is strongly suspected.
Investigation by femtosecond transient absorption of the excited-state dynamics and photophysical processes of two SBPa molecules substituted symmetrically on the betaine phenylene ring by two thiophene (Th
2
SBPa) or bi-thiophene (Th
4
SBPa) units.
The photophysical and nonlinear absorption properties of an oligo(phenylenethienylene)s series (
nTBT
) are investigated in this article. The length of the chromophore is gradually increased from one ...to four phenylenethienylene repeating units in order to evaluate the effects of the electronic delocalization on the two-photon absorption cross sections (
δ
). According to the excitation anisotropy measurements and quantum chemical calculations, two electronic transitions with distinctive symmetries, 1A
g
→ 1B
u
and 1A
g
→ 2A
g
, are present in the low energy region of the linear absorption spectrum. The lowest-energy transition 1A
g
→ 1B
u
is one-photon allowed but two-photon forbidden and implies an electronic charge delocalization all along the oligomer segment whereas the weakly-allowed 1A
g
→ 2A
g
transition exhibits a transition moment perpendicular to the average plane of the chromophore. The latter transition mainly contributes to the two-photon absorption ability of the oligomers. All derivatives are poorly solvatochromic and the breakdown of the mirror symmetry rule observed between absorption and fluorescence spectra at room temperature has been attributed to a photoinduced geometrical relaxation leading to a very efficient planarization process of the oligomer irrespective of its size. Increasing the oligomer length results in a slight shift of the two-photon absorption band (∼1300 cm
−1
) and in a drastic increase of
δ
from 2 ± 1 GM up to 802 ± 160 GM for
1TBT
and
4TBT
respectively. Based on a three-level model, it was found that main contributions to the strong increase of
δ
stem from the transition moments
M
ge
and
M
ee′
which are multiplied by a factor of 2.8 and 5 when going from
1TBT
to
4TBT
.
Insight into the main factors impacting the two-photon absorption properties of a linear oligo(phenylenethienylene)s series.
eskimo1-5 (esk1-5) is a dwarf Arabidopsis (Arabidopsis thaliana) mutant that has a constitutive drought syndrome and collapsed xylem vessels, along with low acetylation levels in xylan and mannan. ...ESK1 has xylan O-acetyltransferase activity in vitro. We used a suppressor strategy on esk1-5 to screen for variants with wild-type growth and low acetylation levels, a favorable combination for ethanol production. We found a recessive mutation in the KAKTUS (KAK) gene that suppressed dwarfism and the collapsed xylem character, the cause of decreased hydraulic conductivity in the esk1-5 mutant. Backcrosses between esk1-5 and two independent knockout kak mutants confirmed suppression of the esk1-5 effect. kak single mutants showed larger stem diameters than the wild type. The KAK promoter fused with a reporter gene showed activity in the vascular cambium, phloem, and primary xylem in the stem and hypocotyl. However, suppression of the collapsed xylem phenotype in esk1 kak double mutants was not associated with the recovery of cell wall O-acetylation or any major cell wall modifications. Therefore, our results indicate that, in addition to its described activity as a repressor of endoreduplication, KAK may play a role in vascular development. Furthermore, orthologous esk1 kak double mutants may hold promise for ethanol production in crop plants.
Gynodioecy, the coexistence of hermaphrodites and females (i.e. male-sterile plants) in natural plant populations, most often results from polymorphism at genetic loci involved in a particular ...interaction between the nuclear and cytoplasmic genetic compartments (cytonuclear epistasis): cytoplasmic male sterility (CMS). Although CMS clearly contributes to the coevolution of involved nuclear loci and cytoplasmic genomes in gynodioecious species, the occurrence of CMS genetic factors in the absence of sexual polymorphism (cryptic CMS) is not easily detected and rarely taken in consideration. We found cryptic CMS in the model plant Arabidopsis thaliana after crossing distantly related accessions, Sha and Mr-0. Male sterility resulted from an interaction between the Sha cytoplasm and two Mr-0 genomic regions located on chromosome 1 and chromosome 3. Additional accessions with either nuclear sterility maintainers or sterilizing cytoplasms were identified from crosses with either Sha or Mr-0. By comparing two very closely related cytoplasms with different male-sterility inducing abilities, we identified a novel mitochondrial ORF, named orf117Sha, that is most likely the sterilizing factor of the Sha cytoplasm. The presence of orf117Sha was investigated in worldwide natural accessions. It was found mainly associated with a single chlorotype in accessions belonging to a clade predominantly originating from Central Asia. More than one-third of accessions from this clade carried orf117Sha, indicating that the sterilizing-inducing cytoplasm had spread in this lineage. We also report the coexistence of the sterilizing cytoplasm with a non-sterilizing cytoplasm at a small, local scale in a natural population; in addition a correlation between cytotype and nuclear haplotype was detected in this population. Our results suggest that this CMS system induced sexual polymorphism in A. thaliana populations, at the time when the species was mainly outcrossing.
To investigate whether P-glycoprotein (P-gp) and multidrug resistance proteins (MRPs), which limit the bioavailability of HIV protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors ...(NRTIs), modulate the anti-HIV activity of NRTIs, non-NRTIs and PIs in vitro.
We used primary cultures of major HIV target cells: human monocyte-derived macrophages (MDMs) and lymphocytes.
P-gp and MRP expression in response to long-term zidovudine (3'-azido-3'-deoxythymidine; AZT) or indinavir treatment was quantified by RT-PCR. MDM and lymphocytes were infected in vitro with HIV-1/Ba-L and HIV-1-LAI, respectively, and treated with antiretroviral drugs. We evaluated the activity of these drugs in combination with PSC833, a P-gp inhibitor, and/or probenecid, an MRP1 inhibitor. Intracellular AZT triphosphate derivative (AZT-TP) was quantified by HPLC-MSMS. P-gp ATPase activity was measured with inside-out native membrane vesicles enriched in P-gp.
Levels of MDR1, mrp4 and mrp5 mRNA were high following AZT treatment. In infected MDM, PSC833 and probenecid increased the anti-HIV activity of AZT and indinavir. AZT (5 nM) decreased HIV replication by 34% alone and by 72% in combination with P-gp/MRP inhibitors. Indinavir (10 nM) gave 14% inhibition alone and 81% in combination. The increase in anti-HIV activity of AZT was correlated with an increase in intracellular AZT-TP concentration. However, unlike PIs, neither AZT nor its metabolites interacted with P-gp.
AZT increases the expression of multidrug transporters, thereby decreasing its pharmacological activity. The cellular efflux of AZT probably involves MRP4 or MRP5. In contrast, increases in indinavir anti-HIV activity require the inhibition of both P-gp and MRP1.
Objective: To assess whether a demented patient with urinary incontinence (UI) could learn to use an adapted version of timed voiding (i.e., instead of being led by a caregiver, the patient learns to ...perform timed voiding by herself). Indeed, UI affects a large number of patients with dementia and creates a substantial burden to the caregiver. UI is the most common complaint at the time of institutionalization and it is often the cause of premature institutionalization. Timed voiding is a promising intervention, but one whose effectiveness remains to be demonstrated. Additionally, timed voiding has the disadvantage of being constraining for caregivers, requiring them to be present to stimulate the patient to urinate at each of the scheduled occasions. Method: The present intervention required the patient to learn (1) to associate an auditory signal from a timer to the action of urination, (2) to reprogram the timer, using the spaced retrieval technique. An ABAB paradigm was used to assess the effectiveness of this program to eliminate urinary accidents. Results: The results of the intervention showed that the use of the timer was effective in helping the patient to reduce her urinary leaks from 1.5 diurnal accidents per week to zero during four months. Conclusion: UI in patients with dementia seems treatable. Such intervention could contribute to delay institutionalization of patients with dementia through maintaining their autonomy and reducing the burden of caregivers.
The growing array of in vitro models of the blood–brain barrier (BBB) which have been used makes it difficult to draw firm conclusions concerning the BBB penetration of HIV-1 protease inhibitors. ...What is needed is a combined in vivo and in vitro study on biological models that mimic as closely as possible the normal human BBB, to establish whether and how indinavir crosses the BBB. We developed a new human BBB model using primary endothelial cells and astrocytes. The biological relevance of this model was checked with respect on the one hand, to the close relationship between the log of drug permeability coefficient normalized to molecular weight and the log of the 1-octanol/water partition coefficient, and on the other hand to the functional P-glycoprotein (P-gp) expression. We employed this model to perform transport studies with indinavir and showed that the rate of in vitro indinavir transport from the basal to apical compartment was higher than the rate of apical to basal transport. Pretreatment of the BBB model with the P-gp inhibitor, quinidine, significantly increased apical to basal transport. Intracellular indinavir accumulation was increased in BBB as a result of inhibition of active transport. These data were correlated with the indinavir-mediated P-gp ATPase modulation showing that indinavir specifically interacted with a binding site on P-gp. Moreover, the activation of P-gp ATPase by indinavir was inhibited by quinidine. In addition, the in vivo brain to plasma concentration ratio of indinavir into mice showed that indinavir concentration was up to five times higher in the brain of
mdr1a(−/−) mice than in the brain of
mdr1a(+/+) mice. All these results confirm the role of P-gp in preventing the passage of indinavir across BBB and thus its entry into the central nervous system (CNS). Our human BBB model represents a useful tool for the evaluation of drug penetration into the CNS.
eskimo1-5 (esk1-5)is a dwarf Arabidopsis (Arabidopsis thaliana) mutant that has a constitutive drought syndrome and collapsed xylem vessels, along with low acetylation levels in xylan andmannan. ESK1 ...has xylanO-acetyltransferase activity in vitro. We used a suppressor strategy onesk1-5to screen for variants with wild-type growth and low acetylation levels, a favorable combination for ethanol production. We found a recessive mutation in theKAKTUS (KAK)gene that suppressed dwarfism and the collapsed xylem character, the cause of decreased hydraulic conductivity in theesk1-5mutant. Backcrosses betweenesk1-5and two independent knockoutkakmutants confirmed suppression of theesk1-5effect.kaksingle mutants showed larger stem diameters than the wild type. TheKAKpromoter fused with a reporter gene showed activity in the vascular cambium, phloem, and primary xylem in the stem and hypocotyl. However, suppression of the collapsed xylem phenotype inesk1 kakdouble mutants was not associated with the recovery of cell wallO-acetylation or any major cell wall modifications. Therefore, our results indicate that, in addition to its described activity as a repressor of endoreduplication, KAK may play a role in vascular development. Furthermore, orthologousesk1 kakdouble mutants may hold promise for ethanol production in crop plants.
Inactivation of ubiquitin-ligase3 suppresses dwarfism and irregular xylem in an Arabidopsis mutant, generating a line with low acetylated biomass and high glucose release after cellulolysis.
eskimo1
...-5
(
esk1-5
) is a dwarf Arabidopsis (
Arabidopsis thaliana
) mutant that has a constitutive drought syndrome and collapsed xylem vessels, along with low acetylation levels in xylan and mannan. ESK1 has xylan
O
-acetyltransferase activity in vitro. We used a suppressor strategy on
esk1-5
to screen for variants with wild-type growth and low acetylation levels, a favorable combination for ethanol production. We found a recessive mutation in the
KAKTUS
(
KAK
) gene that suppressed dwarfism and the collapsed xylem character, the cause of decreased hydraulic conductivity in the
esk1-5
mutant. Backcrosses between
esk1-5
and two independent knockout
kak
mutants confirmed suppression of the
esk1-5
effect.
kak
single mutants showed larger stem diameters than the wild type. The
KAK
promoter fused with a reporter gene showed activity in the vascular cambium, phloem, and primary xylem in the stem and hypocotyl. However, suppression of the collapsed xylem phenotype in
esk1 kak
double mutants was not associated with the recovery of cell wall
O
-acetylation or any major cell wall modifications. Therefore, our results indicate that, in addition to its described activity as a repressor of endoreduplication, KAK may play a role in vascular development. Furthermore, orthologous
esk1 kak
double mutants may hold promise for ethanol production in crop plants.
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