Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation

To identify rate-limiting steps in T cell-independent type 2 (TI-2) antibody production against polysaccharide antigens, we performed a genome-wide screen by immunizing several hundred pedigrees of C57BL/6 mice segregating ENU-induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were isolated that semi-dominantly diminished antibody against polysaccharide but not protein antigens. Both mutations resulted from single amino acid substitutions within the kinase domain of Protein Kinase C Beta (PKCβ). In Tilcara, a Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulting in almost complete loss of active, autophosphorylated PKCβI whereas the amount of alternatively spliced PKCβII protein was not markedly reduced. Circulating B cell subsets were normal and acute responses to BCR-stimulation such as CD25 induction and initiation of DNA synthesis were only measurably diminished in Tilcara homozygotes, whereas the fraction of cells that had divided multiple times was decreased to an intermediate degree in heterozygotes. These results, coupled with evidence of numerous mis-sense PRKCB mutations in the human genome, identify Prkcb as a genetically sensitive step likely to contribute substantially to population variability in anti-polysaccharide antibody levels

Development of physical and mathematical models for the Porous Ceramic Tube Plant Nutrification System (PCTPNS)

A physical model of the Porous Ceramic Tube Plant Nutrification System (PCTPNS) was developed through microscopic observations of the tube surface under various operational conditions. In addition, a mathematical model of this system was developed which incorporated the effects of the applied suction pressure, surface tension, and gravitational forces as well as the porosity and physical dimensions of the tubes. The flow of liquid through the PCTPNS was thus characterized for non-biological situations. One of the key factors in the verification of these models is the accurate and rapid measurement of the 'wetness' or holding capacity of the ceramic tubes. This study evaluated a thermistor based moisture sensor device and recommendations for future research on alternative sensing devices are proposed. In addition, extensions of the physical and mathematical models to include the effects of plant physiology and growth are also discussed for future research

RasGRP1 Transduces Low-Grade TCR Signals which Are Critical for T Cell Development, Homeostasis, and Differentiation

AbstractTwo important Ras-guanyl nucleotide exchange factors, Sos and RasGRP1, control Ras activation in thymocytes. However, the relative contribution of these two exchange factors to Ras/ERK activation and their resulting impact on positive and negative selection is unclear. We have produced two lines of RasGRP1−/− TCR transgenic mice to determine the effect of RasGRP1 in T cell development under conditions of defined TCR signaling. Our results demonstrate that RasGRP1 is crucial for thymocytes expressing weakly selecting TCRs whereas those that express stronger selecting TCRs are more effective at utilizing RasGRP1-independent mechanisms for ERK activation and positive selection. Analysis of RasGRP1−/− peripheral T cells also revealed hitherto unidentified functions of RasGRP1 in regulating T cell homeostasis and sustaining antigen-induced developmental programming

Numerical analysis of spray-dic modeling for fruit concentration drying process into powder based on computational fluid dynamic

The drying process is most popular preservation methods. It is important in producing the powder and natural dye by concentration fruit drying. Spray-DIC is one of the concentration techniques for drying process using the nozzle flow application in computational fluid dynamic. The mathematical modeling for drying process in this paper includes mass conservation and energy conservation of fruit concentration based on partial differential equation. The discretization of mathematical model will use the finite difference method with the initial and boundary conditions of nozzle flow application. The mathematical modeling computes numerical in sequential algorithm. Jacobi and Gauss-Seidel scheme will use to solve the linear system of mathematical modeling. The execution time, no of iteration, accuracy, root mean square error and maximum error are measured for investigating the numerical analysis. The results show the Gauss Seidel method is the alternative method compared to Jacobi method for solving the Spray-DIC modeling

Real-time information processing of environmental sensor network data using Bayesian Gaussian processes

In this article, we consider the problem faced by a sensor network operator who must infer, in real time, the value of some environmental parameter that is being monitored at discrete points in space and time by a sensor network. We describe a powerful and generic approach built upon an efficient multi-output Gaussian process that facilitates this information acquisition and processing. Our algorithm allows effective inference even with minimal domain knowledge, and we further introduce a formulation of Bayesian Monte Carlo to permit the principled management of the hyperparameters introduced by our flexible models. We demonstrate how our methods can be applied in cases where the data is delayed, intermittently missing, censored, and/or correlated. We validate our approach using data collected from three networks of weather sensors and show that it yields better inference performance than both conventional independent Gaussian processes and the Kalman filter. Finally, we show that our formalism efficiently reuses previous computations by following an online update procedure as new data sequentially arrives, and that this results in a four-fold increase in computational speed in the largest cases considered

Synthetic gene design - The rationale for codon optimization and implications for molecular pharming in plants.

Degeneracy in the genetic code allows multiple codon sequences to encode the same protein. Codon usage bias in genes is the term given to the preferred use of particular synonymous codons. Synonymous codon substitutions had been regarded as "silent" as the primary structure of the protein was not affected; however, it is now accepted that synonymous substitutions can have a significant effect on heterologous protein expression. Codon optimization, the process of altering codons within the gene sequence to improve recombinant protein expression, has become widely practised. Multiple inter-linked factors affecting protein expression need to be taken into consideration when optimizing a gene sequence. Over the years, various computer programmes have been developed to aid in the gene sequence optimization process. However, as the rulebook for altering codon usage to affect protein expression is still not completely understood, it is difficult to predict which strategy, if any, will design the 'optimal' gene sequence. In this review, codon usage bias and factors affecting codon selection will be discussed and the evidence for codon optimization impact will be reviewed for recombinant protein expression using plants as a case study. These developments will be relevant to all recombinant expression systems, however, molecular pharming in plants is an area which has consistently encountered difficulties with low levels of recombinant protein expression, and should benefit from an evidence based rational approach to synthetic gene design

2′,3,4,4′-Tetra­meth­oxy­chalcone

In the title compound [systematic name: 1-(2,4-dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one], C19H20O5, the dihedral angle between the benzene rings is 26.88 (5)°. One of the meth­oxy groups is twisted slightly away from the plane [C—O—C—C torsion angle = −12.8 (3)°] while the others are almost co-planer [C—O—C—C torsion angles = −3.2 (3), 2.6 (3) and −3.6 (3)°]. The crystal packing is stabilized by inter­molecular C—H⋯O inter­actions. A weak intra­molecular C—H⋯O inter­action occurs

Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene

The possible relationship of selenium to immunological function which has been suggested for decades was investigated in studies on selenuim metabolism in human T cells. One of the major 75Se-labeled selenoproteins detected was purified to homogeneity and shown to be a homodimer of 55-kDa subunits. Each subunit contained about 1 FAD and at least 0.74 Se. This protein proved to be thioredoxin reductase (TR) on the basis of its catalytic activities, cross-reactivity with anti-rat liver TR antibodies, and sequence identities of several tryptic peptides with the published deduced sequence of human placental TR. Physicochemical characteristics of T-cell TR were similar to those of a selenocysteine (Secys)- containing TR recently isolated from human lung adenocarcinoma cells. The sequence of a 12-residue 75Se-labeled tryptic peptide from T-cell TR was identical with a C-terminaldeduced sequence of human placental TR except that Secys was present in the position corresponding to TGA, previously thought to be the termination codon, and this was followed by Gly-499, the actual C-terminal amino acid. The presence of the unusual conserved Cys-Secys-Gly sequence at the C terminus of TR in addition to the redox active cysteines of the Cys-Val- Asn-Val-Gly-Cys motif in the FAD-binding region may account for the peroxidase activity and the relatively low substrate specificity of mammalian TRs. The finding that T-cell TR is a selenoenzyme that contains Se in a conserved Cterminal region provides another example of the role of selenium in a major antioxidant enzyme system (i.e., thioredoxin- thioredoxin reductase), in addition to the well-known glutathione peroxidase enzyme system