Functional expression of TcoAT1 reveals it to be a P1-type nucleoside transporter with no capacity for diminazene uptake

It has long been established that the Trypanosoma brucei TbAT1/P2 aminopurine transporter is involved in the uptake of diamidine and arsenical drugs including pentamidine, diminazene aceturate and melarsoprol. Accordingly, it was proposed that the closest Trypanosoma congolense paralogue, TcoAT1, might perform the same function in this parasite, and an apparent correlation between a Single Nucleotide Polymorphism (SNP) in that gene and diminazene tolerance was reported for the strains examined. Here, we report the functional cloning and expression of TcoAT1 and show that in fact it is the syntenic homologue of another T. brucei gene of the same Equilibrative Nucleoside Transporter (ENT) family: TbNT10. The T. congolense genome does not seem to contain a syntenic equivalent to TbAT1. Two TcoAT1 alleles, differentiated by three independent SNPs, were expressed in the T. brucei clone B48, a TbAT1-null strain that further lacks the High Affinity Pentamidine Transporter (HAPT1); TbAT1 was also expressed as a control. The TbAT1 and TcoAT1 transporters were functional and increased sensitivity to cytotoxic nucleoside analogues. However, only TbAT1 increased sensitivity to diamidines and to cymelarsan. Uptake of [3H]-diminazene was detectable only in the B48 cells expressing TbAT1 but not TcoAT1, whereas uptake of [3H]-inosine was increased by both TcoAT1 alleles but not by TbAT1. Uptake of [3H]-adenosine was increased by all three ENT genes. We conclude that TcoAT1 is a P1-type purine nucleoside transporter and the syntenic equivalent to the previously characterised TbNT10; it does not mediate diminazene uptake and is therefore unlikely to play a role in diminazene resistance in T. congolense

Business failures and entrepreneurship in international perspective

Onderzoek naar bedrijfsopheffingen in Europese landen, in het bijzonder Nederland, en de Verenigde Staten. De algemene aanname dat de faillissementen licht procyclisch zijn, wordt ondersteund door een tijdreeksanalyse tussen 1980 en 1995. Verder blijken zeer kleine bedrijven (tot en met 9 werknemers) minder faillissementsgevoelig te zijn dan grotere bedrijven.

Person to Person in Japan

While still in the midst of their study abroad experiences, students at Linfield College write reflective essays. Their essays address issues of cultural similarity and difference, compare lifestyles, mores, norms, and habits between their host countries and home, and examine changes in perceptions about their host countries and the United States. In this essay, Stacey Strovink describes her observations during her study abroad program at Kanto Gakuin University in Yokohama, Japan

Emergence of the second law out of reversible dynamics

Abstract If one demystifies entropy the second law of thermodynamics comes out as an emergent property entirely based on the simple dynamic mechanical laws that govern the motion and energies of system parts on a micro-scale. The emergence of the second law is illustrated in this paper through the development of a new, very simple and highly efficient technique to compare time-averaged energies in isolated conservative linear large scale dynamical systems. Entropy is replaced by a notion that is much more transparent and more or less dual called ectropy. Ectropy has been introduced before but we further modify the notion of ectropy such that the unit in which it is expressed becomes the unit of energy. The second law of thermodynamics in terms of ectropy states that ectropy decreases with time on a large enough time-scale and has an absolute minimum equal to zero. Zero ectropy corresponds to energy equipartition. Basically we show that by enlarging the dimension of an isolated conservative linear dynamical system and the dimension of the system parts over which we consider time-averaged energy partition, the tendency towards equipartition increases while equipartition is achieved in the limit. This illustrates that the second law is an emergent property of these systems. Finally from our large scale linear dynamic model we clarify Loschmidt’s paradox concerning the irreversible behavior of ectropy obtained from the reversible dynamic laws that govern motion and energy at the micro-scal

Preservation of panorama mesdag, the Haque

This paper deals with the preservation of the Panorama Mesdag, a cylindrical painting, more than 14 meters high and 120 meters in circumference. The vista of the sea, the dunes and Scheveningen village was painted by one of the most famous painters of the Hague School, Hendrik Willem Mesdag. It is the oldest 19th century panorama in the world in its original site and a unique cultural heritage. About three years ago the building, which is a uniquely complex structure, was damaged by a nearby excavation. In the years to follow a series of measures have been taken of which the compensation grouting of the foundation is the most extensive from a geotechnical point of view.\ud This paper outlines the history of the damage, the construction of the building and most importantly the extents of the compensation grouting and the result of the grouting and the extensive monitoring. The effectiveness of the grouting is determined and conclusions have been drawn for the still to be performed excavations and construction activities

Including copy number variation in association studies to predict genotypic values

The objective of this study was to investigate, both empirically and deterministically, the ability to explain genetic variation resulting from a copy number polymorphism (CNP) by including the CNP, either by its genotype or by a continuous derivation thereof, alone or together with a nearby single nucleotide polymorphism (SNP) in the model. This continuous measure of a CNP genotype could be a raw hybridization measurement, or a predicted CNP genotype. Results from simulations showed that the linkage disequilibrium (LD) between an SNP and CNP was lower than LD between two SNPs, due to the higher mutation rate at the CNP loci. The model R2 values from analysing the simulated data were very similar to the R2 values predicted with the deterministic formulae. Under the assumption that x copies at a CNP locus lead to the effect of x times the effect of 1 copy, including a continuous measure of a CNP locus in the model together with the genotype of a nearby SNP increased power to explain variation at the CNP locus, even when the continuous measure explained only 15% of the variation at the CNP locus