In many biological materials with a hierarchical structure there is an intriguing and unique mechanism responsible for the 'propagation' of order from the molecular to the nano-or micro-scale level. Here we present a much simpler molecular system built of achiral mesogenic dimeric molecules that shows a similar complexity with four levels of structural chirality (i) layer chirality, (ii) helicity of a basic 4-layer repeating unit, (iii) a helix with a pitch of several layers and (iv) mesoscopic helical filaments. As seen in many biological systems, there is a coupling between chirality at different levels. The structures were identified by a combination of hard and soft x-ray diffraction measurements, optical studies and theoretical modelling.One Sentence Summary: Simple molecular system exhibits complex hierarchical structure with chirality coupling between different structural levels.

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OBJECTIVE -To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) Ͼ50 ml/min.RESEARCH DESIGN AND METHODS -FGF21 was determined by enzyme-linked immunosorbent assay in control (n ϭ 60) and CD (n ϭ 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.RESULTS -Median serum FGF21 levels were Ͼ15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR Ͼ50 ml/min (201.9 ng/l) (P Ͻ 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P Ͻ 0.05).CONCLUSIONS -FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects. Diabetes Care 32:126-128, 2009R ecently, fibroblast growth factor 21 (FGF21) was introduced as a novel adipokine with potent antidiabetic properties (1-4). In contrast to extensive experiments in animals, only one study to date has determined regulation and function of FGF21 in humans in vivo (5), and no data have been published about the relation of this adipokine to renal function. RESEARCH DESIGN AND METHODS -The design of the study has been described in detail recently (6 -8). Briefly, 120 Caucasian men (n ϭ 62) and women (n ϭ 58) were recruited with 60 patients having a glomerular filtration rate (GFR) Ͼ50 ml/min (control subjects) as assessed by the original Modification of Diet in Renal Disease formula (9) and 60 patients being on chronic hemodialysis (CD). A total of 30 control subjects and 32 CD patients had type 2 diabetes. The study was approved by the local ethics committee, and all subjects gave written informed consent before taking part in the study. AssaysBlood samples were taken after an overnight fast. In CD patients, blood was drawn just before hemodialysis started. FGF21 (Biovendor, Modrice, Czech Republic), adiponectin (Mediagnost, Reutlingen, Germany), and leptin (Mediagnost) were determined with enzyme-linked immunosorbent assays according to the manufacturer's instructions. Statistical analysisStatistical analyses are specified in RESULTS and in the Table 1 legend. Table 1 summarizes clinical characteristics of the subgroups studied (control, CD) further divided into nondiabetic and diabetic subjects. Median circulating FGF21 was Ͼ15-fold higher in CD patients (3,710.6 Ϯ 5,541.3 ng/l) compared with control subjects (201.9 Ϯ 275.5 ng/l) (P Ͻ 0.001) ( Table 1). Furthermore, FGF21 serum levels were significantly higher in men (1,959.0 Ϯ 4,505.5 ng/l) compared with women (446.9 Ϯ 1,609.0 ng/l) (P Ͻ 0.05) but did not depend on type 2 diabetes. RESULTS FGF21 serum levels are increased in CD patients Univariate correlationsUsing the Spearman's rank correlation method, serum FGF21 concentrations positively correlated with BMI (r ϭ 0.33, 95% CI 0.08 -0.54, P ϭ ...

crux of the issue, the specific manner in which the trans double bonds are positioned within the taxane framework, was deduced through the combined adaptation of one-bond *H/13C COSY correlation and NOE experiments.13 Several of the more diagnostic measurements are given in the illustrations.Molecular mechanics calculations (MODEL version KS 2.96)14 provided indication that 9 might be as much as 3 kcal/mol more thermodynamically stable than 10. Indeed, heating 10 in C6D6 at 67 °C resulted in its unidirectional conversion to 9, k¡ = 2.58 X 10"4 s'1, / j ^2 = 45 min. The relative ease of this diastereomeric interconversion places 10 closer to franr-cyclononene (t[/2 = 4 min at 0 eC)3 23than to frans-cyclooctene (f1/2 = 122 h at 132.7 °C)lc in the intrinsic ability of these molecules to overcome their internal rotational barriers. The thermal stability of 10 is, however, more than adequate to allow for its individual utilization in synthesis, thus providing a new dimension to this area of chemistry.Both 9 and 10 undergo osmylation to give diols 11a (60%) and 12a (84%), respectively, by electrophilic attack from the only available direction external to the ring. Subsequent acetylation provided lib and 12b efficiently.In summary, this study has established the feasibility of controlling stereochemistry by means of rotationally restrictive nonbonded interactions and laid the groundwork for possible entry to various taxanes including 1 by this useful tactic. Our current efforts are focused on these applications.Acknowledgment. We are grateful to the Bristol-Myers Squibb Company for their financial support, to Dr. Dirk Friedrich for his assistance with the NMR experiments, and to Eugene Hickey for the molecular modeling studies. (12) (a) Chapman, O. L.

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