Ala-504 is a determinant of substrate binding affinity in the mouse Na+/dicarboxylate cotransporter

AbstractThe Na+/dicarboxylate cotransporters from mouse (mNaDC1) and rabbit (rbNaDC1) differ in their ability to handle adipate, a six-carbon terminal dicarboxylic acid. The mNaDC1 and rbNaDC1 amino acid sequences are 75% identical. The rbNaDC1 does not transport adipate and only succinate produced inward currents under two-electrode voltage clamp. In contrast, oocytes expressing mNaDC1 had adipate-dependent inward currents that were about 60% of those induced by succinate. In order to identify domains involved in adipate transport, we examined the functional properties of a series of chimeric transporters made between mouse and rabbit NaDC1. We find that multiple transmembrane helices (TM), particularly TM 8, 9, and 10, are involved in adipate transport. In TM 10 there is only one amino acid difference between the two proteins, corresponding to Ala-504 in mouse and Ser-512 in rabbit NaDC1. The mNaDC1-A504S mutant had decreased adipate-dependent currents relative to succinate-dependent currents and an increase in the K0.5 for both succinate and glutarate. We conclude that multiple amino acids from TM 8, 9 and 10 contribute to the transport of adipate in NaDC1. Furthermore, Ala-504 in TM 10 is an important determinant of K0.5 for both adipate and succinate

A fractional kinetic process describing the intermediate time behaviour of cellular flows

This paper studies the intermediate time behaviour of a small random perturbation of a periodic cellular flow. Our main result shows that on time scales shorter than the diffusive time scale, the limiting behaviour of trajectories that start close enough to cell boundaries is a fractional kinetic process: A Brownian motion time changed by the local time of an independent Brownian motion. Our proof uses the Freidlin-Wentzell framework, and the key step is to establish an analogous averaging principle on shorter time scales. As a consequence of our main theorem, we obtain a homogenization result for the associated advection-diffusion equation. We show that on intermediate time scales the effective equation is a fractional time PDE that arises in modelling anomalous diffusion

Identification of transport pathways for citric acid cycle intermediates in the human colon carcinoma cell line, Caco-2

AbstractCitric acid cycle intermediates are absorbed from the gastrointestinal tract through carrier-mediated mechanisms, although the transport pathways have not been clearly identified. This study examines the transport of citric acid cycle intermediates in the Caco-2 human colon carcinoma cell line, often used as a model of small intestine. Inulin was used as an extracellular volume marker instead of mannitol since the apparent volume measured with mannitol changed with time. The results show that Caco-2 cells contain at least three distinct transporters, including the Na+-dependent di- and tricarboxylate transporters, NaDC1 and NaCT, and one or more sodium-independent pathways, possibly involving organic anion transporters. Succinate transport is mediated mostly by Na+-dependent pathways, predominantly by NaDC1, but with some contribution by NaCT. RT-PCR and functional characteristics verified the expression of these transporters in Caco-2 cells. In contrast, citrate transport in Caco-2 cells occurs by a combination of Na+-independent pathways, possibly mediated by an organic anion transporter, and Na+-dependent mechanisms. The non-metabolizable dicarboxylate, methylsuccinate, is also transported by a combination of Na+-dependent and -independent pathways. In conclusion, we find that multiple pathways are involved in the transport of di- and tricarboxylates by Caco-2 cells. Since many of these pathways are not found in human intestine, this model may be best suited for studying Na+-dependent transport of succinate by NaDC1

Modeling of radiation damage in silicon solar cells

One MeV electron irradiation produces preponderantly isolated vacancy interstitial pairs. If neither of these defects is mobile, the concentration of each grows linearly with fluence. Annealing of damage depends on the nature of the damage. Vacancy interstitial pairs which are bound by an interaction such that they mutually annihilate rather than dissociate are termed close pairs; close pair recovery usually occurs at a lower temperature than the temperature at which long distance defect migration occurs. Annealing of the remaining frozen in damage occurs when a temperature is reached where the vacancy or interstitial is mobile; usually the interstitial is more mobile than the vacancy. The recovery occurs in two regimes which may be resoluable

Mixing at Young Ages Reduces Fighting in Unacquainted Domestic Pigs

Under normal farming practices, piglets from different litters are often mixed around the time of weaning, and a high incidence of fighting and minor injuries often occur. The aim of this experiment was to determine the effect of age on the incidence of fighting in piglets mixed before weaning, at different ages between 5 and 26 days. We found no significant relationship between age and the likelihood that a pair of piglets would fight during the first 75 min after mixing. However, the duration of the first fight observed increased from 101±38 s at 5 days to 621±278 s at 26 days, mainly because of higher levels of unretaliated harassment and resting during the bouts. Younger pigs also showed 80% fewer injuries from the fighting. The results suggest some potential welfare advantage to allowing litters to mix at younger ages

A Scientific Conception of Animal Welfare that Reflects Ethical Concerns

Scientific research on \u27animal welfare\u27 began because of ethical concerns over the quality of life of animals, and the public looks to animal welfare research for guidance regarding these concerns. The conception of animal welfare used by scientists must relate closely to these ethical concerns if the orientation of the research and the interpretation of the findings is to address them successfully. At least three overlapping ethical concerns are commonly expressed regarding the quality of life of animals: (1) that animals should lead natural lives through the development and use of their natural adaptations and capabilities, (2) that animals should feel well by being free from prolonged and intense fear, pain, and other negative states, and by experiencing normal pleasures, and (3) that animals should function well, in the sense of satisfactory health, growth and normal functioning of physiological and behavioural systems. Various scientists have proposed restricted conceptions of animal welfare that relate to only one or other of these three concerns. Some such conceptions are based on value positions about what is truly important for the quality of life of animals or about the nature of human responsibility for animals in their care. Others are operational claims: (1) that animal welfare research must focus on the functioning of animals because subjective experiences fall outside the realm of scientific enquiry, or (2) that studying the functioning of animals is sufficient because subjective experiences and functioning are closely correlated. We argue that none of these positions provides fully satisfactory guidance for animal welfare research. We suggest instead that ethical concerns about the quality of life of animals can be better captured by recognizing three classes of problems that may arise when the adaptations possessed by an animal do not fully correspond to the challenges posed by its current environment. (1) If animals possess adaptations that no longer serve a significant function in the new environment, then unpleasant subjective experiences may arise, yet these may not be accompanied by significant disruption to biological functioning. Thus, a bucket-fed calf may experience a strong, frustrated desire to suck, even though it obtains adequate milk. (2) If the environment poses challenges for which the animal has no corresponding adaptation, then functional problems may arise, yet these may not be accompanied by significant effects on subjective feelings. Thus, a pig breathing polluted air may develop lung damage without appearing to notice or mind the problem. (3) Where animals have adaptations corresponding to the kinds of environmental challenges they face, problems may still arise if the adaptations prove inadequate. For example, an animal\u27s thermoregulatory adaptations may be insufficient in a very cold environment such that the animal both feels poorly and functions poorly. We propose that all three types of problems are causes of ethical concern over the quality of life of animals and that they together define the subject matter of animal welfare science

Speed-Consumption Tradeoff for Electric Vehicle Route Planning

We study the problem of computing routes for electric vehicles (EVs) in road networks. Since their battery capacity is limited, and consumed energy per distance increases with velocity, driving the fastest route is often not desirable and may even be infeasible. On the other hand, the energy-optimal route may be too conservative in that it contains unnecessary detours or simply takes too long. In this work, we propose to use multicriteria optimization to obtain Pareto sets of routes that trade energy consumption for speed. In particular, we exploit the fact that the same road segment can be driven at different speeds within reasonable intervals. As a result, we are able to provide routes with low energy consumption that still follow major roads, such as freeways. Unfortunately, the size of the resulting Pareto sets can be too large to be practical. We therefore also propose several nontrivial techniques that can be applied on-line at query time in order to speed up computation and filter insignificant solutions from the Pareto sets. Our extensive experimental study, which uses a real-world energy consumption model, reveals that we are able to compute diverse sets of alternative routes on continental networks that closely resemble the exact Pareto set in just under a second—several orders of magnitude faster than the exhaustive algorithm

Conflict and Cooperation: Sociobiological Principles and the Behaviour of Pigs

The pig provides many examples of how principles of behavioural ecology and sociobiology can lead to insights into farm animal behaviour. According to parent-offspring conflict theory, parents should tend to give a level of parental investment somewhat below that solicited by the young. When closely confined during lactation, sows can do little to limit the amount of contact with the piglets, and the young stimulate a prolonged, high level of lactation. Certain alternative housing systems allow the sow to limit the stimulation she receives, and the resulting reduction in lactation can actually be advantageous to both parties. Communal care of offspring has both advantages and disadvantages in various species; these may help to explain why communal care occurs to a limited extent in pigs, and why sows isolate their litters in early lactation. Neonatal competition and mortality among newborn piglets have strong parallels in the “facultative siblicide” which adjusts brood size in numerous species of birds. These species typically produce slightly more young than are normally raised, and the number of siblings that survive is determined by the ability of the smaller young to withstand intense competition. The hypothesis that pigs have evolved a similar system of brood reduction may explain why piglet mortality is such an enduring problem and requires solutions different from those that work for other domestic species. Resource defence theory provides a functional framework for studies of aggressive behaviour. Factors determining the defensibility of a resource include its degree of clumping in time and space, and these suggest ways to reduce competition for food and other resources. However, aggression involved in establishing social dominance is more likely to be influenced by manipulating traits of the competing animals (competitive ability, familiarity) rather than the defensibility of resources. We conclude that principles of behavioural ecology and sociobiology provide a useful functional and evolutionary perspective to complement other approaches to the study of farm animal behaviour