Séquences tripeptidiques typiques du collagène: étude conformationnelle quantique

Theoretical and experimental investigations on the conformations of synthetic polytripeptides, with Gly-R₂-R₃ general repetitive sequence, are of great interest for the comprehension of the factors wich contribute to the triple helix stabilization.Using appropriate molecules as models, we have investigated by the PCILO method the intrinsic conformational possibilities of each « in situresidue for the following cases: Gly-imino-imino, Gly-amino-imino and Gly-imino-amino which represent the most important sequences occuring in the primary structure of collagen. The computations were carried out taking into account the two pyrrolidine ring puckerings and the preferential side-chains orientations.Extending our previous work concerning the isomeric polytripeptides Gly-X-Pro and Gly-Pro-X with X {Pro, Phe} we have studied the cases of X {Ala, Ser}. In this brief communication, we present a preliminary synthesis of these recent results.     

Food dependent color patterns inThamnocephalus platyurus Packard (Branchiopoda: Anostraca); a laboratory study

Coloration of phyllopods varies from place to place and from one life stage to another. It ranges from translucent or whitish through gray, blue, green, orange, and reddish. Here, we present experimental evidence for a food- dependent color pattern inThamnocephalus platyurus Packard. The presence or absence of the synthetic pigment trans — — carotene in a baker's yeast diet was the controlling factor. All the 24 old larvae used in the experiment were whitish in color. From day 6 until the end the experiment (day 11), 100% of the shrimps under a diet with synthetic trans — — carotene (treatment 1) exhibited a characteristic color pattern which consisted of an orange color in the cercopods, and in all theracopods; the rest of the body exhibited no particular color. In comparison, 100% of the shrimps under a diet without synthetic trans — — carotene (treatment 2) were whitish throughout the body. In females from treatment 1, the ovaries and oocytes were green-bluish, while in females from treatment 2 the ovaries and oocytes were whitish. No significant differences in survival and growth were found, except that at day 9, there was a significant difference in growth, the females with the synthetic trans — — carotene group growing faster.     

Topological classification of RNA structures

We present a novel topological classification of RNA secondary structures with pseudoknots. It is based on the topological genus of the circular diagram associated to the RNA base-pair structure. The genus is a positive integer number whose value quantifies the topological complexity of the folded RNA structure. In such a representation, planar diagrams correspond to pure RNA secondary structures and have zero genus, whereas non-planar diagrams correspond to pseudoknotted structures and have higher genus. The topological genus allows for the definition of topological folding motifs, similar in spirit to those introduced and commonly used in protein folding. We analyze real RNA structures from the databases Worldwide Protein Data Bank and Pseudobase and classify them according to their topological genus. For simplicity, we limit our analysis by considering only Watson-Crick complementary base pairs and G-U wobble base pairs. We compare the results of our statistical survey with existing theoretical and numerical models. We also discuss possible applications of this classification and show how it can be used for identifying new RNA structural motifs.     

Chirality in Distorted Square Planar Pd(O,N)2 Compounds

Salicylidenimine palladium(II) complexes trans‐Pd(O,N)₂ adopt step and bowl arrangements. A stereochemical analysis subdivides 52 compounds into 41 step and 11 bowl types. Step complexes with chiral N‐substituents and all the bowl complexes induce chiral distortions in the square planar system, resulting in Δ/Λ configuration of the Pd(O,N)₂ unit. In complexes 1 , 2 , 3 , 4 , 5 , 6 with enantiomerically pure N‐substituents ligand chirality entails a specific square chirality and only one diastereomer assembles in the lattice. Dimeric Pd(O,N)₂ complexes with bridging N‐substituents in trans‐arrangement are inherently chiral. For dimers 7 , 8 , 9 , 10 , 11 different chirality patterns for the Pd(O,N)₂ square are observed. The crystals contain racemates of enantiomers. In complex 12 two independent molecules form a tight pair. The (R_C) configuration of the ligand induces the same Δ chirality in the Pd(O,N)₂ units of both molecules with varying square chirality due to the different crystallographic location of the independent molecules. In complexes 13 and 14 atrop isomerism induces specific configurations in the Pd(O,N)₂ bowl systems. The square chirality is largest for complex 15 [(Diop)Rh(PPh₃)Cl)], a catalyst for enantioselective hydrogenation. In the lattice of 15 two diastereomers with the same (R_C,R_C) configuration in the ligand Diop but opposite Δ and Λ square configurations co‐crystallize, a rare phenomenon in stereochemistry. Chirality 25:663–667, 2013. © 2013 Wiley Periodicals, Inc.     

Socioeconomic and Sociodemographic Factors Associated with Asthma Related Outcomes in Early Childhood: The Generation R Study

Rationale

Few studies have analyzed the association of socioeconomic and sociodemographic factors with asthma related outcomes in early childhood, including Fraction of exhaled Nitric Oxide (FeNO) and airway resistance (Rint). We examined the association of socioeconomic and sociodemographic factors with wheezing, asthma, FeNO and Rint at age 6 years. Additionally, the role of potential mediating factors was studied.

Methods

The study included 6717 children participating in The Generation R Study, a prospective population-based cohort study. Data on socioeconomic and sociodemographic factors, wheezing and asthma were obtained by questionnaires. FeNO and Rint were measured at the research center. Statistical analyses were performed using logistic and linear regression models.

Results

At age 6 years, 9% (456/5084) of the children had wheezing symptoms and 7% (328/4953) had asthma. Children from parents with financial difficulties had an increased risk of wheezing (adjusted Odds Ratio (aOR) = 1.63, 95% Confidence Interval (CI):1.18–2.24). Parental low education, paternal unemployment and child''s male sex were associated with asthma, independent of other socioeconomic or sociodemographic factors (aOR = 1.63, 95% CI:1.24–2.15, aOR = 1.85, 95% CI:1.11–3.09, aOR = 1.58, 95% CI:1.24–2.01, respectively). No socioeconomic or gender differences in FeNO were found. The risks of wheezing, asthma, FeNO and Rint measurements differed between ethnic groups (p<0.05). Associations between paternal unemployment, child''s sex, ethnicity and asthma related outcomes remained largely unexplained.

Conclusions

This study showed differences between the socioeconomic and sociodemographic correlates of wheezing and asthma compared to the correlates of FeNO and Rint at age 6 years. Several socioeconomic and sociodemographic factors were independently associated with wheezing and asthma. Child''s ethnicity was the only factor independently associated with FeNO. We encourage further studies on underlying pathways and public health intervention programs, focusing on reducing socioeconomic or sociodemographic inequalities in asthma.     

The Mauthner cell half a century later: a neurobiological model for decision-making?

The Mauthner (M) cell is a critical element in a vital escape "reflex" triggered by abrupt or threatening events. Its properties at the molecular and synaptic levels, their various forms of plasticity, and the design of its networks, are all well adapted for this survival function. They guarantee that this behavior is appropriately unilateral, variable, and unpredictable. The M cell sets the behavioral threshold, and, acting in concert with other elements of the brainstem escape network, determines when, where, and how the escape is executed.     

Anti-Cancer Potential of MAPK Pathway Inhibition in Paragangliomas–Effect of Different Statins on Mouse Pheochromocytoma Cells

To date, malignant pheochromocytomas and paragangliomas (PHEOs/PGLs) cannot be effectively cured and thus novel treatment strategies are urgently needed. Lovastatin has been shown to effectively induce apoptosis in mouse PHEO cells (MPC) and the more aggressive mouse tumor tissue-derived cells (MTT), which was accompanied by decreased phosphorylation of mitogen-activated kinase (MAPK) pathway players. The MAPK pathway plays a role in numerous aggressive tumors and has been associated with a subgroup of PHEOs/PGLs, including K-RAS-, RET-, and NF1-mutated tumors. Our aim was to establish whether MAPK signaling may also play a role in aggressive, succinate dehydrogenase (SDH) B mutation-derived PHEOs/PGLs. Expression profiling and western blot analysis indicated that specific aspects of MAPK-signaling are active in SDHB PHEOs/PGLs, suggesting that inhibition by statin treatment could be beneficial. Moreover, we aimed to assess whether the anti-proliferative effect of lovastatin on MPC and MTT differed from that exerted by fluvastatin, simvastatin, atorvastatin, pravastatin, or rosuvastatin. Simvastatin and fluvastatin decreased cell proliferation most effectively and the more aggressive MTT cells appeared more sensitive in this respect. Inhibition of MAPK1 and 3 phosphorylation following treatment with fluvastatin, simvastatin, and lovastatin was confirmed by western blot. Increased levels of CASP-3 and PARP cleavage confirmed induction of apoptosis following the treatment. At a concentration low enough not to affect cell proliferation, spontaneous migration of MPC and MTT was significantly inhibited within 24 hours of treatment. In conclusion, lipophilic statins may present a promising therapeutic option for treatment of aggressive human paragangliomas by inducing apoptosis and inhibiting tumor spread.     

Criteria for Viability Assessment of Discarded Human Donor Livers during Ex Vivo Normothermic Machine Perfusion

Although normothermic machine perfusion of donor livers may allow assessment of graft viability prior to transplantation, there are currently no data on what would be a good parameter of graft viability. To determine whether bile production is a suitable biomarker that can be used to discriminate viable from non-viable livers we have studied functional performance as well as biochemical and histological evidence of hepatobiliary injury during ex vivo normothermic machine perfusion of human donor livers. After a median duration of cold storage of 6.5 h, twelve extended criteria human donor livers that were declined for transplantation were ex vivo perfused for 6 h at 37°C with an oxygenated solution based on red blood cells and plasma, using pressure controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion. During perfusion, two patterns of bile flow were identified: (1) steadily increasing bile production, resulting in a cumulative output of ≥30 g after 6 h (high bile output group), and (2) a cumulative bile production <20 g in 6 h (low bile output group). Concentrations of transaminases and potassium in the perfusion fluid were significantly higher in the low bile output group, compared to the high bile output group. Biliary concentrations of bilirubin and bicarbonate were respectively 4 times and 2 times higher in the high bile output group. Livers in the low bile output group displayed more signs of hepatic necrosis and venous congestion, compared to the high bile output group. In conclusion, bile production could be an easily assessable biomarker of hepatic viability during ex vivo machine perfusion of human donor livers. It could potentially be used to identify extended criteria livers that are suitable for transplantation. These ex vivo findings need to be confirmed in a transplant experiment or a clinical trial.