Synthesis and structure–activity relationships of PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives

Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway by PI3K/mTOR dual inhibitors provides a promising new approach to the treatment of cancers. In this Letter, we identified structurally novel and potent PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives. Their synthesis and structure–activity relationships are reported.     

Turnover of cell surface-bound capsular polysaccharide in Staphylococcus aureus

The capsular polysaccharide (CPS) of Staphylococcus aureus strain Smith was labelled by growth of bacteria in the presence of radioactive N-acetylglucosamine and was separated from labelled cell wall components by affinity chromatography on wheat germ agglutinin following dissolution of the cells by lysostaphin. The products were partially characterised chemically and immunochemically. Similar labelled components were found in the culture fluid during growth. In a pulse-chase experiment, cell-bound CPS was released continuously into the culture fluid at the same rate as cell wall turnover and there was no evidence of direct excretion of CPS.     

Mapping of neuropeptide Y expression in Octopus brains

Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation in Octopus. However, little is known about the precise molecular circuitry of NPY-mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout the Octopus central nervous system. The sequence analysis of Octopus NPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians. In situ hybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY-dependent modulation in Octopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of the Octopus feeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in various Octopus behaviors.     

Metabolic Reconfiguration in C. elegans Suggests a Pathway for Widespread Sterol Auxotrophy in the Animal Kingdom

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Central Place Foraging in Nonpatchy Habitats

This paper deal with a model of optimal foraging in a habitat with arbitrary food distribution. It takes into account an arbitrary risk cost related to the distance to the animal's nest. Food acquisition and risk cost are accounted for in common units of fitness. The resulting problem is solved in the context of Calculus of Variations. The optimal duration of absence from the nest and the optimal spatial allocation of foraging time are obtained: the optimal strategy leads to separate the habitat into a region to exploit and a region to ignore. The definition of these two distinct regions depends on the relative importance of risk and food availability. With realistic risk costs, the resulting strategy indicates a highly selective behaviour when far from the nest, as observed in field studies. The model is also extended to take account of the need of returning to the nest to guard it or to feed the young.     

Effect of arm-shoulder fatigue on carpenters at work

The purpose of the study was to analyse the effect of arm-shoulder fatigue on manual performance. Ten experienced carpenters performed three standardized tasks (nailing, sawing and screwing). Electromyographic activity was recorded from six arm-shoulder muscles and the performances were video-filmed. After 45 min of standardized arm-cranking (arm-shoulder-fatiguing exercise of approximately 70%-80% maximal oxygen consumption), the tasks were repeated. The number of work movements and the time taken for each task were recorded and the quality of the work performed was compared. After the fatiguing exercise, only nailing was perceived as being harder and more mistakes were made during nailing and sawing. Movement performance was not influenced during nailing but was slightly slower during sawing and faster during screwing. However, there were increased mean EMG amplitudes in the upper trapezius and biceps muscles during nailing, in the upper trapezius, anterior deltoid and infraspinatus muscles during sawing and in the anterior deltoid muscle during screwing. Of the muscles studied the upper trapezius and anterior deltoid muscles increased their activity most after the arm-shoulder-fatiguing exercise.     

Denitrifying population dynamic and evolution of nitrogen gas during a composting process

Abstract Little information exists about nitrogen losses through microbial activity during treatment of solid urban waste (SUW) by processes such as composting. In the present study, in addition to evaluating the pattern of nitrogen losses by denitrification at different stages of the process, a comparison between the method of Pochon and Tardieux, and an improved gas chromatographic method for estimating denitrifying populations was undertaken, Though the MPN (Most Probable Number) enumerations were higher using the colorimetric method than the gas chromatographic one, the patterns of the two graphs showing numbers of denitrifiers during composing were the same. The highest numbers were revealed immediately after loading the reactor (10⁷–10⁸/g d.w.), lower numbers of denitrifiers were found in the second sampling corresponding to the thermophilic phase (10³–10⁴/g d.w.). These numbers increased gradually as the waste material stabilized (10th to 123rd day of composting) to again reach values of 10⁷–10⁸/g d.w.