Computing by nowhere increasing complexity

A cellular automaton is presented whose governing rule is that the Kolmogorov complexity of a cell's neighborhood may not increase when the cell's present value is substituted for its future value. Using an approximation of this two-dimensional Kolmogorov complexity the underlying automaton is shown to be capable of simulating logic circuits. It is also shown to capture trianry logic described by a quandle, a non-associative algebraic structure. A similar automaton whose rule permits at times the increase of a cell's neighborhood complexity is shown to produce animated entities which can be used as information carriers akin to gliders in Conway's game of life

Non-Inertial Quantum Clock Frames Lead to Non-Hermitian Dynamics

The operational approach to time is a cornerstone of relativistic theories, as evidenced by the notion of proper time. In standard quantum mechanics, however, time is an external parameter. Recently, many attempts have been made to extend the notion of proper time to quantum mechanics within a relational framework. Here, we use similar ideas combined with the relativistic mass-energy equivalence to study an accelerating massive quantum particle with an internal clock system. We show that the ensuing evolution from the perspective of the particle’s internal clock is non-Hermitian. This result does not rely on specific implementations of the clock. As a particular consequence, we prove that the effective Hamiltonian of two gravitationally interacting particles is non-Hermitian from the perspective of the clock of either particle

Effects of frequent machine milking and suckling in early lactation on blood plasma ion homoeostasis in high-yielding dairy cows

SUMMARY Groups of nine or ten cows were assigned, after calving, to treatments in which they were (i) machine milked three times daily (M3), (ii) machine milked six times daily (M6) or (iii) suckled three times daily in addition to being machine milked three times daily (S). Treatments were administered during the first 6 weeks postpartum. On one day, at weeks 1 and 6 postpartum, blood samples were collected from all cows at 30-min intervals between 06.00 and 13.00 h and these were analysed for plasma osmolality and plasma concentrations of Na + , K + and Cl − . Milk yield was significantly higher in suckled cows than in cows milked six times daily, but significantly lower in cows milked three times daily. In cows milked six times daily, and to a greater extent in suckled cows, there was a reduction in plasma osmolality and monovalent ion concentrations (Na + , K + and Cl − ), which could increase the susceptibility of the cows to water intoxication. Moreover, suckling or milking the cows six times daily was associated with increased fluctuations in plasma osmolality and plasma Cl − concentrations. The decrease in plasma osmolality and ion concentration and the increased variation in plasma osmolality and Cl − were probably related to increased water intake and may be indicative of a severe challenge to homoeostasis regulation

Evolution of Plant Nucleotide-Sugar Interconversion Enzymes

Nucleotide-diphospho-sugars (NDP-sugars) are the building blocks of diverse polysaccharides and glycoconjugates in all organisms. In plants, 11 families of NDP-sugar interconversion enzymes (NSEs) have been identified, each of which interconverts one NDP-sugar to another. While the functions of these enzyme families have been characterized in various plants, very little is known about their evolution and origin. Our phylogenetic analyses indicate that all the 11 plant NSE families are distantly related and most of them originated from different progenitor genes, which have already diverged in ancient prokaryotes. For instance, all NSE families are found in the lower land plant mosses and most of them are also found in aquatic algae, implicating that they have already evolved to be capable of synthesizing all the 11 different NDP-sugars. Particularly interesting is that the evolution of RHM (UDP-L-rhamnose synthase) manifests the fusion of genes of three enzymatic activities in early eukaryotes in a rather intriguing manner. The plant NRS/ER (nucleotide-rhamnose synthase/epimerase-reductase), on the other hand, evolved much later from the ancient plant RHMs through losing the N-terminal domain. Based on these findings, an evolutionary model is proposed to explain the origin and evolution of different NSE families. For instance, the UGlcAE (UDP-D-glucuronic acid 4-epimerase) family is suggested to have evolved from some chlamydial bacteria. Our data also show considerably higher sequence diversity among NSE-like genes in modern prokaryotes, consistent with the higher sugar diversity found in prokaryotes. All the NSE families are widely found in plants and algae containing carbohydrate-rich cell walls, while sporadically found in animals, fungi and other eukaryotes, which do not have or have cell walls with distinct compositions. Results of this study were shown to be highly useful for identifying unknown genes for further experimental characterization to determine their functions in the synthesis of diverse glycosylated molecules

Crystal structure of the Ego1-Ego2-Ego3 complex and its role in promoting Rag GTPase-dependent TORC1 signaling

The target of rapamycin complex 1 (TORC1) integrates various hormonal and nutrient signals to regulate cell growth, proliferation, and differentiation. Amino acid-dependent activation of TORC1 is mediated via the yeast EGO complex (EGOC) consisting of Gtr1, Gtr2, Ego1, and Ego3. Here, we identify the previously uncharacterized Ycr075w-a/Ego2 protein as an additional EGOC component that is required for the integrity and localization of the heterodimeric Gtr1-Gtr2 GTPases, equivalent to mammalian Rag GTPases. We also report the crystal structure of the Ego1-Ego2-Ego3 ternary complex (EGO-TC) at 2.4 Å resolution, in which Ego2 and Ego3 form a heterodimer flanked along one side by Ego1. Structural data also reveal the structural conservation of protein components between the yeast EGO-TC and the human Ragulator, which acts as a GEF for Rag GTPases. Interestingly, however, artificial tethering of Gtr1-Gtr2 to the vacuolar membrane is sufficient to activate TORC1 in response to amino acids even in the absence of the EGO-TC. Our structural and functional data therefore support a model in which the EGO-TC acts as a scaffold for Rag GTPases in TORC1 signaling

PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer

Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell’s responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention