Bio-availability of three formulations of glibenclamide

Eighteen healthy men participated in a double-blind, randomised, crossover study to compare the bio-availability of three 5 mg formulations of glibenclamide. The products compared were Daonil (Hoechst), Glycomin (Lennon) and Melix (Lagamed). Volunteers received a continuous intravenous infusion of glucose at a rate of 0,25 g/kg/h for 10 hours. Two hours after commencement of this infusion medication was given orally with 200 ml of a 10% (m/v) glucose solution. The subjects also drank 200 ml of the glucose solution hourly for 5 hours after medication. Blood samples were taken up to 22 hours after medication for radio-immunoassay of glibenclamide as well as for measurement of glucose concentrations. The following kinetic variables were calculated; maximum concentration, time to maximum concentration, terminal halflife, areas under the serum concentration-time curves, relative total clearance, total mean time and relative volume of distribution. Daonil and Glycomin were bio-equivalent, but important differences were demonstrated between these two formulations and Melix. This study method necessitates close surveillance of volunteers in order to detect and treat hypoglycaemia.S Afr Med J 1989; 76: 146-14

Влияние магнитомеханического резонанса на амплитудно- и фазочастотные зависимости переменных составляющих эффекта Фарадея

В рамках модели продольных колебаний тонкого стержня из магнитооптического кристалла в условиях магнитомеханического резонанса показано, что вынужденные колебания могут создавать не только амплитудные, но и фазочастотные зависимости переменных составляющих эффекта Фарадея.У рамках моделі поздовжніх коливань тонкого стрижня із магнітооптичного кристала в умовах магнітомеханічного резонансу показано, що вимушені коливання можуть створювати не тільки амплітудні, але й фазочастотні залежності змінних складових ефекту Фарадея.In the framework of a model of longitudinal vibrations of a thin rod fabricated of the magneto-optical crystal under a magnetomechanical resonance, it is shown that the forced oscillations can create not only the amplitude but also phase-frequency dependences of the variable components of the Faraday effect

Architecture and modular assembly of Sulfolobus S-layers revealed by electron cryotomography

This is the final version. Available from the National Academy of Sciences of the United States of America via the DOI in this record. Surface protein layers (S-layers) often form the only structural component of the archaeal cell wall and are therefore important for cell survival. S-layers have a plethora of cellular functions including maintenance of cell shape, osmotic, and mechanical stability, the formation of a semipermeable protective barrier around the cell, and cell-cell interaction, as well as surface adhesion. Despite the central importance of S-layers for archaeal life, their 3-dimensional (3D) architecture is still poorly understood. Here we present detailed 3D electron cryomicroscopy maps of archaeal S-layers from 3 different Sulfolobus strains. We were able to pinpoint the positions and determine the structure of the 2 subunits SlaA and SlaB. We also present a model describing the assembly of the mature S-layer.ER

Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates

AglH, a thermophilic UDP‑<i>N</i>‑acetylglucosamine‑1‑phosphate:dolichyl phosphate GlcNAc‑1‑phosphotransferase initiating protein<i> N</i>‑glycosylation pathway in <i>Sulfolobus acidocaldarius</i>, is capable of complementing the eukaryal Alg7

AglH, a predicted UDP-GlcNAc-1-phosphate:dolichyl phosphate GlcNAc-1-phosphotransferase, is initiating the protein N-glycosylation pathway in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. AglH successfully replaced the endogenous GlcNAc-1-phosphotransferase activity of Alg7 in a conditional lethal Saccharomyces cerevisiae strain, in which the first step of the eukaryal protein N-glycosylation process was repressed. This study is one of the few examples of cross-domain complementation demonstrating a conserved polyprenyl phosphate transferase reaction within the eukaryal and archaeal domain like it was demonstrated for Methanococcus voltae (Shams-Eldin et al. 2008). The topology prediction and the alignment of the AglH membrane protein with GlcNAc-1-phosphotransferases from the three domains of life show significant conservation of amino acids within the different proposed cytoplasmic loops. Alanine mutations of selected conserved amino acids in the putative cytoplasmic loops II (D(100)), IV (F(220)) and V (F(264)) demonstrated the importance of these amino acids for cross-domain AlgH activity in in vitro complementation assays in S. cerevisiae. Furthermore, antibiotic treatment interfering directly with the activity of dolichyl phosphate GlcNAc-1-phosphotransferases confirmed the essentiality of N-glycosylation for cell survival

Future landscapes: managing within complexity

A regional landscape is a complex social–ecological system comprising a dynamic mosaic of land uses. Management at this scale requires an understanding of the myriad interacting human and natural processes operating on the landscape over a continuum of spatial and temporal scales.Complexity science, which is not part of traditional management approaches, provides a valuable conceptual framework and quantitative tools for dealing with cross-scale interactions and non-linear dynamics in social–ecological systems. Here, we identify concepts and actions arising from complexity science that can be learned and applied by ecosystem managers and discuss how they might be implemented to achieve sustainable future landscapes.Lael Parrott and Wayne S Meye

A fusion of salient and convolutional features applying healthy templates for MRI brain tumor segmentation

This paper proposes an improved brain tumor segmentation method based on visual saliency features on MRI image volumes. The proposed method introduces a novel combination of multiple MRI modalities used as pseudo-color channels for highlighting the potential tumors. The novel pseudo-color model incorporates healthy templates generated from the MRI slices without tumors. The constructed healthy templates are also used during the training of neural network models. Based on a saliency map built using the pseudo-color templates, combination models are proposed, fusing the saliency map with convolutional neural networks’ prediction maps to improve predictions and to reduce the networks’ eventual overfitting which may result in weaker predictions for previously unseen cases. By introducing the combination technique for deep learning techniques and saliency-based, handcrafted feature models, the fusion approach shows good abstraction capabilities and it is able to handle diverse cases that the networks were less trained for. The proposed methods were tested on the BRATS2015 and BRATS2018 databases, and the quantitative results show that hybrid models (including both trained and handcrafted features) can be promising alternatives for reaching higher segmentation performance. Moreover, healthy templates can provide additional information for the training process, enhancing the prediction performance of neural network models

Effects of N-Glycosylation Site Removal in Archaellins on the Assembly and Function of Archaella in Methanococcus maripaludis

In Methanococcus maripaludis S2, the swimming organelle, the archaellum, is composed of three archaellins, FlaB1S2, FlaB2S2 and FlaB3S2. All three are modified with an N-linked tetrasaccharide at multiple sites. Disruption of the N-linked glycosylation pathway is known to cause defects in archaella assembly or function. Here, we explored the potential requirement of N-glycosylation of archaellins on archaellation by investigating the effects of eliminating the 4 N-glycosylation sites in the wildtype FlaB2S2 protein in all possible combinations either by Asn to Glu (N to Q) substitution or Asn to Asp (N to D) substitutions of the N-glycosylation sequon asparagine. The ability of these mutant derivatives to complement a non-archaellated ΔflaB2S2 strain was examined by electron microscopy (for archaella assembly) and swarm plates (for analysis of swimming). Western blot results showed that all mutated FlaB2S2 proteins were expressed and of smaller apparent molecular mass compared to wildtype FlaB2S2, consistent with the loss of glycosylation sites. In the 8 single-site mutant complements, archaella were observed on the surface of Q2, D2 and D4 (numbers after N or Q refer to the 1st to 4th glycosylation site). Of the 6 double-site mutation complementations all were archaellated except D1,3. Of the 4 triple-site mutation complements, only D2,3,4 was archaellated. Elimination of all 4 N-glycosylation sites resulted in non-archaellated cells, indicating some minimum amount of archaellin glycosylation was necessary for their incorporation into stable archaella. All complementations that led to a return of archaella also resulted in motile cells with the exception of the D4 version. In addition, a series of FlaB2S2 scanning deletions each missing 10 amino acids was also generated and tested for their ability to complement the ΔflaB2S2 strain. While most variants were expressed, none of them restored archaellation, although FlaB2S2 harbouring a smaller 3-amino acid deletion was able to partially restore archaellation

Prefrontal dopamine and the dynamic control of human long-term memory

Dopaminergic projections to the prefrontal cortex support higher-order cognitive functions, and are critically involved in many psychiatric disorders that involve memory deficits, including schizophrenia. The role of prefrontal dopamine in long-term memory, however, is still unclear. We used an imaging genetics approach to examine the hypothesis that dopamine availability in the prefrontal cortex selectively affects the ability to suppress interfering memories. Human participants were scanned via functional magnetic resonance imaging while practicing retrieval of previously studied target information in the face of interference from previously studied non-target information. This retrieval practice (RP) rendered the non-target information less retrievable on a later final test—a phenomenon known as retrieval-induced forgetting (RIF). In total, 54 participants were genotyped for the catechol-O-methyltransferase (COMT) Val108/158Met polymorphism. The COMT Val108/158Met genotype showed a selective and linear gene-dose effect on RIF, with the Met allele, which leads to higher prefrontal dopamine availability, being associated with greater RIF. Mirroring the behavioral pattern, the functional magnetic resonance imaging data revealed that Met allele carriers, compared with Val allele carriers, showed a greater response reduction in inhibitory control areas of the right inferior frontal cortex during RP, suggesting that they more efficiently reduced interference. These data support the hypothesis that the cortical dopaminergic system is centrally involved in the dynamic control of human long-term memory, supporting efficient remembering via the adaptive suppression of interfering memories