Prokineticin receptor identified by phage display is an entry receptor for Trypanosoma cruzi into mammalian cells.

Trypanosoma cruzi trypomastigotes invade a great variety of mammalian cells, with several molecules being implicated in this complex event. Herein, the sequence GGIALAG present in prokineticin-2 receptor (PKR2), selected by phage display technology, is described as a new T. cruzi receptor for the Tc85 group of glycoproteins belonging to the gp85/TS superfamily and involved in cellular invasion of mammalian hosts. This finding is confirmed by the inhibitory activity of MCF10-A (human mammary) cell invasion by T. cruzi either by anti-PKR2 antibodies (77%) or GGIALAG-synthetic peptide (42%). Furthermore, interference RNA (iRNA) inhibition of PKR2 expression in MCF10-A cells reduces T. cruzi invasion by 50%. The binding site of Tc85 to PKR2 was localized at the C-terminal end of the molecule, upstream of the conserved FLY sequence, previously implicated in parasite cell invasion. PKR2, a receptor formed by seven membrane-spanning α-helical segments, is mainly present in the central nervous system, peripheral organs, and mature blood cells. Due to its wide distribution, PKR2 could be a suitable receptor for T. cruzi natural infection, contributing to the parasite dissemination throughout the mammalian organism. These findings augment the number and diversity of possible in vivo receptors for T. cruzi and reassure the multiplicity of Tc85 binding sites to mammalian hosts.

Mechanisms of simple and choice reaction to changes in direction of visual motion.

Experiments are presented in which a random dot pattern moved vertically upwards (velocity vector V(1)) and then abruptly changed its direction of motion by the angle alpha (velocity vector V(2)), either to the left or to the right, without changing the speed. Subjects performed simple reactions to the direction change, disregarding its sign. In another experiment choice reactions to the same stimuli were performed: the subjects pushed a left button when the direction change was to the left and a right button when the change was to the right. The simple reaction time decreased monotonically with alpha increasing from 11 degrees to 169 degrees, whereas, within the same range of angles, a U-shaped curve described the function of the choice reaction time versus alpha. Both types of reaction time increased with decreasing the base speed. Difficulties are outlined which occur when the angle of change alpha is considered as 'intensity' of the stimulus. Instead, the parameter mid R:V(2)-V(1)mid R:, the absolute value of the difference between the velocity vectors before and after the change, is shown to be a meaningful 'intensity' parameter for the simple reaction task. The parameter V(2N), the speed of the velocity component normal to the initial velocity vector V(1), is suggested as an 'intensity' parameter for the choice reaction task. It is shown that the simple and choice reactions to changes in direction of visual motion are performed by two distinct mechanisms which seem to work in parallel and may be nearly equally fast for small angles of change, when mid R:V(2)-V(1)mid R: approximately V(2N).

The discrimination of abrupt changes in speed and direction of visual motion.

A random dot pattern that moved within an invisible aperture was used to present two motions contiguously in time. The motions differed slightly either in speed (Experiments 1 and 3) or in direction (Experiments 2 and 4) and the subject had to discriminate the sign of the change (e.g. increment or decrement). The same discrimination task was performed when the two motions were temporally separated by 1 s. In Experiments 1 and 2 discrimination thresholds were measured with motion durations of 0.125, 0.25, 0.5 and 1.0 s and mean speeds of 2, 4, 8, and 16 degrees/s. In Experiments 3 and 4 thresholds were measured with aperture widths of 5 and 20 cm. The discrimination of contiguous motions progressively deteriorated with decreasing duration and mean speed of motion. For the lowest value of duration the Weber fraction for contiguous speeds was more than three times as the Weber fractions for separate speeds. For the same low value of duration the thresholds for discrimination of direction of contiguous motions were only about 50% higher than the thresholds for separate motions. The Weber fraction for contiguous speeds was ca. three times higher with the smaller aperture than with the larger one, provided the ratio 'aperture width mean speed' (i.e. the lifetime of the moving dots) was less than 0.3 s. Aperture width did not affect the discrimination of direction of contiguous motions. The discrimination of contiguous motions is discussed together with the known data for detection of changes in speed and direction. It is suggested that both, detection of changes in speed and discrimination of the sign of speed changes, may be performed by a common visual mechanism.

The simple reaction time to changes in direction of visual motion.

Recently Dzhafarov et al. presented a model explaining data on simple reaction time (RT) to unidimensional velocity changes. The authors suggested that having a motion with an initial velocity V0, the velocity change detection system is reinitialized by means of a "subtractive normalization" process. Therefore, any abrupt change from V0 to V1 is detected as if it were the onset of motion with a speed equal to /V1-V0/. They derived that the RT is a function of /V1-V0/(-2/3). We tested this model for the case of two-dimensional velocity changes. Our subjects observed a random dot pattern that moved horizontally, then changed the direction of motion by an angle alpha in the range between 6 degrees and 180 degrees without changing the speed V. Speeds of 4 and 12 deg/s were used. The subjects reacted as quickly as possible to the direction change. The RTs asymptotically decreased with increasing alpha; with 12 deg/s speed the RTs were shorter than those obtained with 4 deg/s. It was shown that the data can be well described as a function of /V1-V0/(-2/3)=(2Vsin(alpha/2))(-2/3). An extension of the "subtractive normalization" hypothesis for the case of two-dimensional velocity changes is proposed. It is based on the assumption that the velocity vector V1 after the change is decomposed into two orthogonal components. Alternative explanations based on the use of position or orientation cues are shown to contradict the data.