Type I collagen is the major structural component of lung stroma. Because of its long half-life, type I collagen undergoes post-translational modifications such as glycation during aging process. ...These modifications have been shown to impact the structural organization of type I collagen fibers. In the present work we evaluated the impact of collagen aging on lung carcinoma cells response to erlotinib-induced cytotoxicity and apoptosis, and on Epidermal Growth Factor Receptor (EGFR) expression and phosphorylation. To this end, experiments were performed in 2D and 3D matrix models established from type I collagen extracted from adult (10 weeks-old) and old (100 weeks-old) rat's tail tendons. Our results show that old collagen induces a significant increase in EGFR expression and phosphorylation when compared to adult collagen in 3D matrix but not in 2D coating. Such modification was associated to an increase in the IC
50
of erlotinib in the presence of old collagen and a lower sensitivity to drug-induced apoptosis. These data suggest that collagen aging confers resistance to the cytotoxic and apoptotic effects of therapies targeting EGFR kinase function in lung carcinoma. Moreover, our data underline the importance of the 3D matrix environment in this process.
The first families of alkaline-earth stannylides Ae(SnPh
3
)
2
·(thf)
x
(Ae = Ca,
x
= 3,
1
; Sr,
x
= 3,
2
; Ba,
x
= 4,
3
) and Ae{Sn(SiMe
3
)
3
}
2
·(thf)
x
(Ae = Ca,
x
= 4,
4
; Sr,
x
= 4,
5
; Ba,
...x
= 4,
6
), where Ae is a large alkaline earth with direct Ae-Sn bonds, are presented. All complexes have been characterised by high-resolution solution NMR spectroscopy, including
119
Sn NMR, and by X-ray diffraction crystallography. The molecular structures of Ca(SnPh
3
)
2
·(thf)
4
(
1′
), Sr(SnPh
3
)
2
·(thf)
4
(
2′
), Ba(SnPh
3
)
2
·(thf)
5
(
3′
),
4
,
5
and Ba{Sn(SiMe
3
)
3
}
2
·(thf)
5
(
6′
), most of which crystallised as higher thf solvates than their parents
1-6
, were established by XRD analysis; the experimentally determined Sn-Ae-Sn′ angles lie in the range 158.10(3)-179.33(4)°. In a given series, the
119
Sn NMR chemical shifts are slightly deshielded upon descending group 2 from Ca to Ba, while the silyl-substituted stannyls are much more shielded than the phenyl ones (
δ
119
Sn/ppm:
1′
, −133.4;
2′
, −123.6;
3′
, −95.5;
4
, −856.8;
5
, −848.2;
6′
, −792.7). The bonding and electronic properties of these complexes were also analysed by DFT calculations. The combined spectroscopic, crystallographic and computational analysis of these complexes provide some insight into the main features of these unique families of homoleptic complexes. A comprehensive DFT study (Wiberg bond index, QTAIM and energy decomposition analysis) points at a primarily ionic Ae-Sn bonding, with a small covalent contribution, in these series of complexes; the Sn-Ae-Sn′ angle is associated with a flat energy potential surface around its minimum, consistent with the broad range of values determined by experimental and computational methods.
The complete series of heterobimetallic alkaline-earth distannyls Ae{SnR
3
}
2
·(thf)
x
(Ae = Ca, Sr, Ba) have been prepared for R = Ph and SiMe
3
, and their bonding and electronic properties have been comprehensively investigated.
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IJS, KILJ, NUK, UL, UM, UPUK
Residues 16–20 of the β-amyloid peptide (Aβ) function as a self-recognition element during Aβ assembly into fibers. Peptides containing this motif retain the ability to interact with Aβ and, in some ...cases, potently inhibit its assembly. Replacing l- with d-amino acids could stabilize such peptides and permit their evaluation as therapeutic agents for Alzheimer's disease. Here we have assessed the effect that such a chiral reversal has on inhibitory potency. d-enantiomers of five peptides, KLVFFA, KKLVFFA, KFVFFA, KIVFFA, and KVVFFA, were unexpectedly more active as inhibitors in an in vitro fibrillogenesis assay. Circular dichroism showed that d-KLVFFA more effectively prevented Aβ adopting the β-sheet secondary structure correlated with fibrillogenesis. Electron microscopy showed that fiber formation was also more strongly inhibited by d-KLVFFA. Heterochiral inhibition was confirmed using d-Aβ, on the principle that enantiomeric proteins exhibit reciprocal chiral biochemical interactions. With d-Aβ, l-KLVFFA was the more potent inhibitor, rather than d-KLVFFA. Most significantly, d-peptides were more potent at reducing the toxicity of both Aβ1–40 and Aβ1–42 toward neuronal cells in culture. This unforeseen heterochiral stereoselectivity of Aβ for d-peptide inhibitors should be considered during future design of peptide-based inhibitors of Aβ neurotoxicity and fibrillogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Therapeutic patient education (TPE) allows elderly as well as young adults to evaluate patient's self-care and adaptation skills to their own clinical condition. Falling is a symptom present in ...various chronic diseases, which leads to loss of autonomy, fear of recidivism and frequent admissions into institutions. Study objective was to evaluate at 3 and 6 months the impact of TPE on fall recurrence, perceived quality of life and fear of falling, in elderly over 75 living at home.
We performed a prospective study comparing two groups: a group participating in day hospital (group "TPE") and a control group (group "Hospitalized") of elderly patient not receiving TPE recruited in short geriatric stays following a fall at home.
28 patients in the "TPE" group and 20 patients in the "Hospitalized" group were included. The "TPE" group reported significantly better perceived quality of life at 3 months and 6 months. At 6 months, fear of falling was twice as high in the "Hospitalized" group than in the "TPE" group.
The group of subjects who was able to benefit from therapeutic education at home had an improved quality of life at 3 and 6 months and a decrease in the fear of falling at 6 months.
Dynamic cationic polymers were generated in aqueous media from functionally complementary monomers bearing nucleobase groups. 1H NMR spectroscopy was used to follow the polycondensation reaction of ...the nucleobase‐appended dihydrazides 1 and 2 with the dialdehydes B and C. The reversibility of these polymers was established by proton NMR spectroscopy through exchange of the dihydrazide 2 with polymer 1 B. The polymers 1 B, 2 B, 1 C, and 2 C represent dynamic biopolymers of nucleic acid type, DyNAs. Electrostatic interaction of these polymers with polyanionic entities, such as polyphosphates, polynucleotides, and polyaspartic acid, was shown to take place. It induces a change in size of the dynamic polymer, as it responds by an increase in degree of polymerization to an increase of the overall anionic charge introduced, that is, to the total electrostatic interaction.
Nucleic acid analogues get dynamic! Components bearing functional groups capable of undergoing reversible connections and appended with nucleobase groups generate reversible covalent polymers that represent dynamic biopolymers, “biodynamers” (see scheme). Such entities display component exchange and undergo modification upon binding of external effectors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In order to further document the relation between redox conditions and the sedimentary record of Mn, U and Mo in a transitory anoxic water basin, their distribution has been studied along two ...profiles in the Thau lagoon (France). Sediments and pore-water have been sampled at two contrasting sites located, respectively, in the shellfish-farming area and in the centre of the lagoon. In the shellfish-farming area, the particulate organic carbon (POC) data indicate a more rapid organic matter mineralisation compared to the centre of the lagoon. This results in a sharper redox gradient characterized by the appearance of H
2S in pore-water a few millimetres below the sediment–water interface. In the centre of the lagoon, H
2S appears at a depth of 35 cm.
In both cores, sedimentary Mn is relatively depleted through out the whole sedimentary column and varies with the proportion of clay minerals. After an initial release into solution at the sediment–water interface in relation to Mn-oxide reductive dissolution, authigenic U is immobilized when sulphides appear. Despite the occurrence of anoxic conditions at the sediment–water interface at the site influenced by shellfish farming, the burial of U is reduced by bioturbation, which raises reducing sediments to the surface. In the centre of the lagoon, Mo profiles reflect continuous diffusion into pore water and immobilization at 15 cm probably in anoxic microenvironments. At shellfish farms, dissolved Mo undergoes removal with sulphides but contrary to U, sedimentary Mo does not appear to be strongly affected by bioturbation. The profile indicates an increase in the frequency of anoxia crises during the second half of the 20th century.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Predictive clinical scores, diagnostic as well as prognostic, are considered to be useful tools for making decisions under conditions of uncertainty. They are not intended to replace clinical ...judgment or medical experience, but to help physicians in the interpretation of clinical information. The general practitioner (GP), the gateway to care in the French health system, should be the main beneficiary of their utilization. However, there is no information on the prevalence of their use in general practice in France.
A national, transversal epidemiological survey was conducted by electronic mail among GPs belonging to the French Sentinelles network. GPs were asked about their use of scores, the context of their utilization and the expected benefit. A qualitative study (focus groups) was also carried out with three groups of GPs within the context of continuous medical education.
The study consisted of 358 GPs. They were questioned on their use of seven predictive clinical scores (six diagnostic and one prognostic). Clinical scores were used by 75% of GPs, with no statistical difference with regard to their age or sex. The most often used were: the Mini Mental Status Examination (MMSE) (95%), Fagerström test (90%), Hamilton scale (65%), McIsaac scores (61%), DETA/CAGE (45%), Simple Calculated Osteoporosis Risk Estimation (SCORE) for osteoporosis (33%), and the only prognostic score CHADS2 (28%). Clinical scores were especially used when elderly people were involved (77%) and when the diagnosis was uncertain (63%). The qualitative study gave additional information on the barriers and obstacles to the use of predictive clinical scores.
This study, the first one in France, gives information on the perception of clinical scores and on the rationale for their use by GPs. Suggestions to improve the situation (availability and rate of utilization of clinical scores) are provided.
Reported here is a readily available bis(imino)carbazole‐based proligand that constitutes a convenient entry point into the challenging synthetic molecular chemistry of barium. It enables the ...preparation of rare or even, up to now, unknown, solution‐stable heteroleptic barium complexes. The syntheses and structural features for the first molecular barium fluoride and the first barium stannylide, with an unsupported Ba−Sn bond, are described, along with other carbazolate barium species: an amide (both a remarkably stable starting material and an excellent hydrophosphination precatalyst), iodide, and silanylide. DFT analysis of bonding patterns in the barium stannylide and barium silanylide highlights a prevailingly ionic barium–tetrelide bond with a small covalent contribution.
Barium rockt! Eine neuer Carbazol‐basierter Ligand, der leicht in großen Mengen erhalten werden kann, ermöglicht die Synthese von bislang unbekannten lösungsstabilen Bariumkomplexen. Beispiele sind Bariumfluorid‐ und Bariumstannylid‐Spezies, die ungewöhnliche Bindungsmuster aufweisen.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
AlInN/AlN/GaN based HEMTs were fabricated on SiC substrate to demonstrate the high potentiality of these heterostructures. The presented results confirm the high performances reachable by AlInN based ...technology with an output power of 6.8W/mm at 10GHz with a gate length of 0.25mum. A good extrinsic transconductance value of 400mS/mm was also measured on these transistors. The results are believed to be the best power results published about AlInN/GaN HEMTs.
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