Mgat1-dependent N-glycans are essential for the normal development of both vertebrate and invertebrate metazoans

UDP-GlcNAc:α3-d-mannoside β1,2-N-acetylglucosaminyltransferase I (GnTI, encoded by Mgat1) first appeared in evolution at about the same time as metazoa suggesting that GnTI-dependent glycans are essential for the development of multicellular organisms. This review describes the effects of mutations in the Mgat1 gene on the development of Caenorhabditis elegans, Drosophila melanogaster and mice.     

Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation

We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state-dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations—such as glucose overbatching and insufficient aeration—on growth, metabolism, and titer.     

Neuromolecular computing: a new approach to human brain evolution

Evolutionary approaches in human cognitive neurobiology traditionally emphasize macroscopic structures. It may soon be possible to supplement these studies with models of human information-processing of the molecular level. Thin-film, simulation, fluorescence microscopy, and high-resolution X-ray crystallographic studies provide evidence for transiently organized neural membrane molecular systems with possible computational properties. This review article examines evidence for hydrophobic-mismatch molecular interactions within phospholipid microdomains of a neural membrane bilayer. It is proposed that these interactions are a massively parallel algorithm which can rapidly compute near-optimal solutions to complex cognitive and physiological problems. Coupling of microdomain activity to permenant ion movements at ligand-gated and voltage-gated channels permits the conversion of molecular computations into neuron frequency codes. Evidence for microdomain transport of proteins to specific locations within the bilayer suggests that neuromolecular computation may be under some genetic control and thus modifiable by natural selection. A possible experimental approach for examining evolutionary changes in neuromolecular computation is briefly discussed. Received: 2 October 1998 / Accepted in revised form: 19 March 1999     

The effect of tetrathiomolybdate on the metabolism of copper by hepatocytes and fibroblasts

Tetrathiomolybdate (TTM) has been examined for its effect on copper metabolism in mouse hepatocytes in primary culture and human fibroblasts. It decreased the amount of copper inside hepatocytes, decreased the rate of copper uptake by hepatocytes in a concentration dependent manner, and increased the copper efflux from the cells. TTM appeared to remove copper preferentially from the labile pool, but with a lower affinity than cage chelators. In fibroblasts, TTM only had a marginal effect on copper levels below a concentration of 100 microM and had no clear effect on the rate of copper uptake. TTM was not toxic to human fibroblasts, but in some preparations, a concentration of more than 50 microM was toxic to hepatocytes.     

A linear function for the melting behavior of lipids

The melting behavior of a variety of saturated long chain compounds is shown to be related to hydrocarbon chain length by the equation TN = C₀ + T_∞N where T is the absolute melting temperature, and N is the number of long chain carbon atoms. The constants C₀ and T_∞ are determined graphically or analytically from TN vs. N data. The linear relationship, derived from fundamental thermodynamic principles, is empirically satisfied. For each homologous series considered, coefficients of the equation provide a rational means for correlation and comparison with other polymorphs and indicate the relative importance of chain length, chain parity (even or odd), and headgroup polarity to melting behavior.     

The Dialectics of Contrast and Continuity in the Films of Humphrey Bogart

In this article I have the following principle aims: first to demonstrate the intertextuality of the film roles of Humphrey Bogart during the decades of the 1930s to the 1950s; second, to show how the transformation of persona in film roles relates to changes in the social and cultural environment of that period; and finally, as an outcome of this examination, I consider the dialectic of contrast and continuity in terms of how it provides an understanding of “otherness.”     

Oogenesis: From Oogonia to Ovulation in the Flagfish,Jordanella floridae Goode and Bean, 1879 (Teleostei: Cyprinodontidae)

We provide histological details of the development of oocytes in the cyprinodontid flagfish, Jordanella floridae. There are six stages of oogenesis: Oogonial proliferation, chromatin nucleolus, primary growth (previtellogenesis [PG]), secondary growth (vitellogenesis), oocyte maturation and ovulation. The ovarian lamellae are lined by a germinal epithelium composed of epithelial cells and scattered oogonia. During primary growth, the development of cortical alveoli and oil droplets, are initiated simultaneously. During secondary growth, yolk globules coalesce into a fluid mass. The full‐grown oocyte contains a large globule of fluid yolk. The germinal vesicle is at the animal pole, and the cortical alveoli and oil droplets are located at the periphery. The disposition of oil droplets at the vegetal pole of the germinal vesicle during late secondary growth stage is a unique characteristic. The follicular cell layer is composed initially of a single layer of squamous cells during early PG which become columnar during early vitellogenesis. During primary and secondary growth stages, filaments develop among the follicular cells and also around the micropyle. The filaments are seen extending from the zona pellucida after ovulation. During ovulation, a space is evident between the oocyte and the zona pellucida. Asynchronous spawning activity is confirmed by the observation that, after ovulation, the ovarian lamellae contain follicles in both primary and secondary growth stages; in contrast, when the seasonal activity of oogenesis and spawning ends, after ovulation, the ovarian lamellae contain only follicles in the primary growth stage. J. Morphol. 277:1339–1354, 2016. © 2016 Wiley Periodicals, Inc.     

Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer’s disease agents

The design, synthesis and assessment of β-carboline core-based compounds as potential multifunctional agents against several processes that are believed to play a significant role in Alzheimer’s disease (AD) pathology, are described. The activity of the compounds was determined in Aβ self-assembly (fibril and oligomer formation) and cholinesterase (AChE, BuChE) activity inhibition, and their antioxidant properties were also assessed. To obtain insight into the mode of action of the compounds, HR-MS studies were carried out on the inhibitor-Aβ complex formation and molecular docking was performed on inhibitor-BuChE interactions. While several compounds exhibited strong activities in individual assays, compound 14 emerged as a promising multi-target lead for the further structure-activity relationship studies.     

Identification of non-catalytic conserved regions in xylanases encoded by the xynB and xynD genes of the cellulolytic rumen anaerobe Ruminococcus flavefaciens

xynB is one of at least four genes from the cellulolytic rumen anaerobe Ruminococcus flavefaciens 17 that encode xylanase activity. The xynB gene is predicted to encode a 781-amino acid product starting with a signal peptide, followed by an amino-terminal xylanase domain which is identical at 89% and 78% of residues, respectively, to the amino-terminal xylanase domains of the bifunctional XynD and XynA enzymes from the same organism. Two separate regions within the carboxy-terminal 537 amino acids of XynB also show close similarities with domain B of XynD. These regions show no significant homology with cellulose- or xylan-binding domains from other species, or with any other sequences, and their functions are unknown. In addition a 30 to 32-residue threonine-rich region is present in both XynD and XynB. Codon usage shows a consistent pattern of bias in the three xylanase genes from R. flavefaciens that have been sequenced.