Re-entrant Nematic Phase Established for Several Homologous Biaromatic Liquid Crystals by Investigation of Binary Mixed Systems

Several homologous series of biaromatic liquid crystals with structure type CnH2n+1O • C6H4 • M•C6H4-CN are investigated. By studying the phase transition temperatures in binary mixed systems a "re-entrant" nematic phase N(re) is established for all compounds exhibiting smectic A phases. The virtual transition temperatures N(re) - SA are found to decrease with increasing chain length of the alkyloxy group. The influence of the middle group M on the re-entrant behaviour can be attributed mainly to its dipole moment. The temperature range of the smectic A phase decreases when the middle group dipole moment is additive to that of the nitrile group. To summarize it can be said that the "re-entrant" behaviour of biaromatic liquid crystals is found to be very similar to that of triaromatic systems reported recently

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

BACKGROUND: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. METHODS: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. RESULTS: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1–6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality. CONCLUSIONS: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event

A target-protection mechanism of antibiotic resistance at atomic resolution: insights into FusB-type fusidic acid resistance

Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance

Temperature independent threshold voltage for an electrooptic effect

The threshold voltage of the cholesteric-nematic phase change effect in general decreases considerably with increasing temperature. The temperature dependence for the threshold voltage can be compensated by using an induced cholesteric phase with a helix pitch decreasing sufficiently with increasing temperature. The appropriate temperature dependence of the pitch can be obtained if the nematic phase is doped with two chiral compounds which induce opposite sign of the helix screw sense when used separately. The efficacy of this method was investigated for the two nematic mixtures E 8 and S 1132 to which the two chiral compounds CB 15 and S 811 had been added, the induced pitch values being 3-5 μm. The threshold voltage measured in samples of 23.5 μm and 13 μm thickness using homeotropic boundary conditions are found to be constant within ± 3 % over a temperature range of 50 K.Normalement la tension seuil de l'effet de transition cholestérique-nématique se réduit considérablement si la température monte. Cette dépendance de la température peut être compensée en utilisant des phases cholestériques induites dont le pas hélicoïdal diminue suffisamment si la température monte. La dépendance souhaitée du pas de l'hélice en fonction de la température est obtenue en mélangeant à la phase nématique deux composés chiraux de signe contraire. Nous présentons ici des résultats obtenus sur des mélanges nématiques E 8 et S 1132 dopés avec les composés chiraux CB 15 et S 811, les valeurs de pas obtenues étant 3-5 μm. La tension seuil mesurée pour des épaisseurs de couches de 23,5 μm et 13 μm respectivement et pour des alignements homéotropes se révèle être constante à ± 3 % dans une gamme de température de 50 K

Long-range allosteric signaling in red light-regulated diguanylyl cyclases.

Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light-sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate-producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine. We anticipate that consideration of molecular principles of sensor-effector coupling, going beyond the length of the characteristic linker, and the appreciation of dynamically driven allostery will open up new directions for the design of novel red light-regulated optogenetic tools

Glucagon-like peptide 1 (GLP-1) drives postprandial hyperinsulinemic hypoglycemia in pregnant women with a history of roux-en-Y gastric bypass operation

BACKGROUND: The influential role of incretin hormones on glucose metabolism in patients with a history of Roux-en-Y gastric bypass (RYGB) has been investigated thoroughly, but there has been little examination of the effect of incretins and ectopic lipids on altered glucose profiles, especially severe hypoglycemia in pregnant women with RYGB. METHODS: In this prospective clinical study, an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and continuous glucose monitoring (CGM) were conducted in 25 women with RYGB during pregnancy, 19 of normal weight (NW) and 19 with obesity (OB) between the 24th and the 28th weeks of pregnancy, and 3 to 6 months post-partum. Post-partum, the ectopic lipid content in the liver, heart, and skeletal muscle was analyzed using 1H-magnetic resonance spectroscopy (1H-MRS). RESULTS: RYGB patients presented with major fluctuations in glucose profiles, including a high occurrence of postprandial hyperglycemic spikes and hypoglycemic events during the day, as well as a high risk of hypoglycemic periods during the night (2.9 ± 1.1% vs. 0.1 ± 0.2% in the OB and vs. 0.8 ± 0.6% in the NW groups, p < 0.001). During the extended OGTT, RYGB patients presented with exaggerated expression of GLP-1, which was the main driver of the exaggerated risk of postprandial hypoglycemia in a time-lagged correlation analysis. Basal and dynamic GLP-1 levels were not related to insulin sensitivity, insulin secretion, or beta cell function and did not differ between pregnant women with and without GDM. A lower amount of liver fat (2.34 ± 5.22% vs.5.68 ± 4.42%, p = 0.015), which was positively related to insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR: rho = 0.61, p = 0.002) and beta-cell function (insulinogenic index: rho = 0.65, p = 0.001), was observed in the RYGB group after delivery in comparison to the OB group. CONCLUSION: GLP-1 is mainly involved in the regulation of postprandial glucose metabolism and therefore especially in the development of postprandial hypoglycemia in pregnant RYGB patients, who are characterized by major alterations in glucose profiles, and thus in long-term regulation, multiple organ-related mechanisms, such as the lipid content in the liver, must be involved. Clinical Trials Registration Number: NCT03190148