High-resolution genomic analysis: the tumor-immune interface comes into focus

A genomic analysis of heterogeneous colorectal tumor samples has uncovered interactions between immunophenotype and various aspects of tumor biology, with implications for informing the choice of immunotherapies for specific patients and guiding the design of personalized neoantigen-based vaccines.Please see related article: http://dx.doi.org/10.1186/s13059-015-0620-6Immunotherapy is a promising new approach for treating human malignancies. Approximately 20% of melanoma and lung cancer patients receiving immune checkpoint inhibitors show responses [1,2]. Current major challenges include identification of patients most likely to respond to specific therapies and elucidation of novel targets to treat those who do not. To address these problems, a detailed understanding of the dynamic interactions between tumors and the immune system is required. In a new study, Zlatko Trajanoski and colleagues [3] describe a powerful approach to dissecting these issues through high-resolution analysis of patient genomic data. This study represents a significant advance over previous work from this group, which defined 28 immune-cell-type gene expression signatures and identified specific cell types as prognostic indicators in colorectal cancer (CRC) patients [4]. Here, the authors [3] integrate genomic analyses of CRC tumor molecular phenotypes, predicted antigenicity (called the ‘antigenome’), and immune-cell infiltration derived from multiple independent cohorts to gain refined insights into tumor-immune system interactions.     

Comparison of genetic algorithms for experimental multi-objective optimization on the example of medium design for cyanobacteria

In this work, two different genetic algorithms were applied to improve culture media composition for the autotrophic cyanobacteria Synechococcus PCC 7942. Biomass yield and conversion of the asymmetric reduction of 2', 3', 4', 5', 6'-pentafluoroacetophenone were considered as simultaneous objectives, resulting in a multi-objective optimization problem. Even when similar performances of both algorithms were observed, it could be shown that a novel strength pareto approach was able to achieve remarkable results with a reduced number of experiments (160 instead of 320). Handling a high number of media components (13), their concentrations were adjusted, delivering high improvements in comparison to the standard BG 11 culture media. The quality of the Synechococcus biocatalyst could be increased up to fivefold compared to the initial state of the optimization.     

Computational experience with an algorithm for tetrangle inequality bound smoothing

An important component of computer programs for determining the solution conformation of proteins and other flexible molecules from nuclear magnetic resonance data are the so-called “bound smoothing algorithms”, which compute lower and upper limits on the values of all the interatomic distances from the relatively sparse set which can usually be measured experimentally. To date, the only methods efficient enough for use in large problems take account of only the triangle inequality, but an appreciable improvement in the precision of the limits is possible if the algebraic relations between the distances among each quadruple of atoms are also considered. The goal of this paper is to use a recently improved algorithm for computing these “tetrangle inequality limits” to determine just how much improvement really is possible, given the types of experimental data that are usually available.     

Cofactor regeneration in phototrophic cyanobacteria applied for asymmetric reduction of ketones

The obligate photoautotrophic cyanobacterium Synechococcus PCC7942 and the photoheterotrophic heterocystous cyanobacterium Noctoc muscorum are able to reduce prochiral ketones asymmetrically to optical pure chiral alcohols without light. An example is the synthesis of S-pentafluoro(phenyl-)ethanol with an enantiomeric excess >99% if 2′-3′-4′-5′-6′-pentafluoroacetophenone is used as substrate. If no light is available for regeneration of the cofactor nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH), glucose is used as cosubstrate. Membrane disintegration during asymmetric reduction promotes cytosolic energy generating metabolic pathways. Observed regulatory effects depicted by an adenosine triphosphate (ATP) to nicotinamide adenine dinucleotide phosphate (oxidized form) (NADP⁺) ratio of 3:1 for efficient cofactor recycling indicate a metabolization via glycolisis. The stoichiometric formation of the by-product acetate (1 mol acetate/1 mol chiral alcohol) indicates homoacetic acid fermentation for cofactor regeneration including the obligate photoautotrophic cyanobacterium Synechococcus PCC7942.     

Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal

We have developed a new approach to the measurement of phylogenetic signal in character state matrices called relative apparent synapomorphy analysis (RASA). RASA provides a deterministic, statistical measure of natural cladistic hierarchy (phylogenetic signal) in character state matrices. The method works by determining whether a measure of the rate of increase of cladistic similarity among pairs of taxa as a function of phenetic similarity is greater than a null equiprobable rate of increase. Our investigation of the utility and limitations of RASA using simulated and bacteriophage T7 data sets indicates that the method has numerous advantages over existing measures of signal. A first advantage is computational efficiency. A second advantage is that RASA employs known methods of statistical inference, providing measurable sensitivity and power. The performance of RASA is examined under various conditions of branching evolution as the number of characters, character states per character, and mutations per branch length are varied. RASA appears to provide an unbiased and reliable measure of phylogenetic signal, and the general approach promises to be useful in the development of new techniques that should increase the rigor and reliability of phylogenetic estimates.      

RT-qPCR reveals opsin gene upregulation associated with age and sex in guppies (Poecilia reticulata) - a species with color-based sexual selection and 11 visual-opsin genes

Background  

PCR-based surveys have shown that guppies (Poecilia reticulata) have an unusually large visual-opsin gene repertoire. This has led to speculation that opsin duplication and divergence has enhanced the evolution of elaborate male coloration because it improves spectral sensitivity and/or discrimination in females. However, this conjecture on evolutionary connections between opsin repertoire, vision, mate choice, and male coloration was generated with little data on gene expression. Here, we used RT-qPCR to survey visual-opsin gene expression in the eyes of males, females, and juveniles in order to further understand color-based sexual selection from the perspective of the visual system.     

Milk Fever Control Principles: A Review

Three main preventive principles against milk fever were evaluated in this literature review, and the efficacy of each principle was estimated from the results of controlled investigations. Oral calcium drenching around calving apparently has a mean efficacy of 50%–60% in terms of milk fever prevention as well as prevention of milk fever relapse after intravenous treatment with calcium solutions. However, some drenches have been shown to cause lesions in the forestomacs. When using the DCAD (dietary cation-anion difference) principle, feeding rations with a negative DCAD (measured as (Na + K) – (Cl + S)) significantly reduce the milk fever incidence. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a mean RR between 0.19 and 0.35 when rations with a negative versus positive DCAD are compared. The main drawback from the DCAD principle is a palatability problem. The principle of feeding rations low in calcium is highly efficient in milk fever prevention provided the calcium intake in the dry period is kept below 20 g per day. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a very low mean RR (between 0 and 0.20) (daily calcium intake below versus above 20 g/d). The main problem in implementing the low-Ca principle is difficulties in formulating rations sufficiently low in calcium when using commonly available feeds. The use of large doses of vitamin D metabolites and analogues for milk fever prevention is controversial. Due to toxicity problems and an almost total lack of recent studies on the subject this principle is not described in detail. A few management related issues were discussed briefly, and the following conclusions were made: It is important to supply the periparturient cow with sufficient magnesium to fulfil its needs, and to prevent the dry cows from being too fat. Available information on the influence of carbohydrate intake, and on the effect of the length of the dry period and prepartum milking, is at present insufficient to include these factors in control programmes.     

Genesis of fatty liver and hyperlipemia in the fetal guinea pig.

10 to 20% of [1-14C] palmitate injected into pregnant guinea pigs was recovered in lipids of their fetuses. From these data and the rate of transport of palmitate in maternal blood, it appears that placental transport of free fatty acids can account for the accumulation of lipids in late gestational fetuses. About 80% of the labeled palmitate in the fetus appeared initially in lipids of the liver. 14C appeared in plasma triglyceride fatty acids after a few minutes and subsequently accumulated in lipids of white and brown adipose tissue, suggesting that much of the palmitate deposited in adipose tissue were derived from hepatogenous triglyceride fatty acids. By contrast, 14C was usually maximal in heart and carcass lipids before it appeared in plasma triglyceride fatty acids. Lipoprotein lipase activity in fetal adipose tissue was low, and activity of cofactor protein of lipoprotein lipase in fetal blood plasma was much lower than that observed in other mammalian species. On the basis of these and earlier observations, it is concluded that the accumulation of triglycerides in liver and blood plasma of fetal guinea pigs during late gestation is at least partly the result of the large uptake of maternally derived free fatty acids by the fetal liver accompanied by rapid synthesis and secretion of triglyceride-rich very low density lipoproteins into the blood. However, limited uptake of triglyceride fatty acids in adipose tissue may contribute to the fatty liver and hyperlipemia.     

Properties of serum high-density lipoproteins in the crab, Cancer antennarius Stimpson

Two classes of high-density lipoprotein (HDL) comprise virtually all the lipoprotein mass in female hemolymph. These lipoproteins have hydrated densities of 1.187 g/ml (HDL3) and 1.112 g/ml (HDL2). A third species (HDL1, density 1.080 g/ml) appeared in ovigerous crabs. The mean annual HDL protein concentration was 109 mg/dl of which 67% was HDL3. HDL proteins of both HDL2 and HDL3 were mostly insoluble in tetramethylurea. Three major components with apparent mol. wts of 185,000, 100,000 and 84,000 daltons were identified by gel electrophoresis in SDS. Amino acid compositions are reported. Electron microscopy indicated that the HDL are polymorphic and discoidal. Similarities in shape and differences in size of HDL3 and HDL2 particles were consistent with their lipid and protein composition. Phospholipids, mostly phosphatidylcholine, were the dominant lipid class (74%); no cholesteryl esters were detected. Palmitic and oleic acids were the major fatty acid components of esterified lipids.     

Shoot production fromin vitro cultured flower heads ofAllium porrum L

Shoots have been produced in the explants from flower head receptacles cultured on BDS medium with BAP and/or NAA. The shoots produced could be regenerated to form the whole plants and transplanted into soil. No morphological or cytological variations were observed in mature plants. The histological analysis of adventive bud formation is presented. The importance of this method for clonal propagation ofAllium porrum plants is discussed.