Transcriptomic and computational analysis identified LPA metabolism, KLHL14 and KCNE3 as novel regulators of Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a complex biological program between physiology and pathology. Here, amniotic epithelial cells (AEC) were used as in vitro model of transiently inducible EMT in order to evaluate the transcriptional insights underlying this process. Therefore, RNA-seq was used to identify the differentially expressed genes and enrichment analyses were carried out to assess the intracellular pathways involved. As a result, molecules exclusively expressed in AEC that experienced EMT (GSTA1-1 and GSTM3) or when this process is inhibited (KLHL14 and KCNE3) were identified. Lastly, the network theory was used to obtain a computational model able to recognize putative controller genes involved in the induction and in the prevention of EMT. The results suggested an opposite role of lysophosphatidic acid (LPA) synthesis and degradation enzymes in the regulation of EMT process. In conclusion, these molecules may represent novel EMT regulators and also targets for developing new therapeutic strategies.

Genetic diversity of Coxiella burnetii in domestic ruminants in central Italy.

BACKGROUND: As the epidemiology of human Q Fever generally reflects the spread of Coxiella burnetii in ruminant livestock, molecular characterization of strains is essential to prevent human outbreaks. In this study we report the genetic diversity of C. burnetii in central Italy accomplished by MST and MLVA-6 on biological samples from 20 goat, sheep and cow farms. RESULTS: Five MST and ten MLVA profiles emerged from the analysis establishing a part of C. burnetii strain world atlas. In particular, ST32 occurred on 12 farms (60%), prevalently in goat specimens, while ST12 (25%) was detected on 4 sheep and 1 goat samples. ST8 and a variant of this genotype were described on 2 different sheep farms, whereas ST55 was observed on a goat farm. Five complete MLVA profiles different from any other published genotypes were described in this study in addition to 15 MLVA incomplete panels. Despite this, polymorphic markers Ms23, Ms24 and Ms33 enabled the identification of samples sharing the same MST profile. CONCLUSIONS: Integration of such data in international databases can be of further help in the attempt of building a global phylogeny and epidemiology of Q fever in animals, with a "One Health" perspective.

The preattentive emperor has no clothes: a dynamic redressing.

Preattentive models of early vision have not been supported by the evidence. Instead, an input filtering system, which is dynamically reconfigured so as to optimize performance on the task at hand, is proposed. As a case in point, the authors examined Sagi and Julesz's (1985a) claim that detection tasks are processed preattentively and efficiently (shallow search slopes), whereas discrimination tasks require focal attention and yield inefficient steep slopes. In 5 visual search experiments, efficiency was found to depend not on the nature of the task but on whether the task is single or dual. The second component of a dual task, whether detection or discrimination, is performed inefficiently if it does not fit the configuration of the input system, which had been set optimally for the first component. But, even the second component is processed efficiently if there is enough time to reconfigure the system after processing the first component.

Attentional requirements is visual detection and identification: evidence from the attentional blink.

Perception of the 2nd of 2 targets (T1 and T2) is impaired if the lag between them is short (0-500 ms). The authors used this attentional blink (AB) to index attentional requirements in detection and identification tasks, with or without backward masking of T2, in 2 stimulus domains (line orientation, coherent motion). With masking, the AB occurred because T2 was masked during the attentional dwell time created by T1 processing (Experiments 1, 2, and 3). Without masking, an AB occurred only in identification because during the attentional dwell time, T2 decayed to a level that could support simple detection but not complex identification. However, an AB occurred also in detection if T2 was sufficiently degraded (Experiment 4). The authors drew 2 major conclusions: (a) Attention is required in both identification and detection, and (b) 2 factors contribute to the AB, masking of T2 while attention is focused on T1 and decay of the T2 trace while unattended.

What's new in visual masking?

A brief display that is clearly visible when shown alone can be rendered invisible by the subsequent presentation of a second visual stimulus. Several recently described backward masking effects are not predicted by current theories of visual masking, including masking by four small dots that surround (but do not touch) a target object and masking by a surrounding object that remains on display after the target object has been turned off. A crucial factor in both of these effects is attention: almost no masking occurs if attention can be rapidly focused on the target, whereas powerful masking ensues if attention directed at the target is delayed. A new theory of visual masking, inspired by developments in neuroscience, can account for these effects, as well as more traditional masking effects. In addition, the new theory sheds light on related research, such as the attentional blink, inattentional blindness and change blindness.

Direct estimates of processing delays in the attentional blink.

When two targets (T1 and T2) are presented in rapid succession, identification of T2 is often impaired (attentional blink: AB). The two-stage model accounts for the AB deficit by assuming that: (a) T2 is delayed in Stage 1 while Stage 2 is busy processing T1, and (b) T2 is vulnerable to masking while delayed. We report converging evidence for the model by evaluating these assumptions independently of the AB deficit itself. The results show that: (a) response times for T2 identification decreased as the lag between T1 and T2 was increased; (b) response times for T2 decreased across lags only if T1 was masked; and (c) accuracy of T2 identification increased as the stimulus-onset asynchrony between T2 and the trailing mask was increased.

Response latencies to the onset and offset of visual stimuli.

Simple response times (RTs) are known to be slower to the offset of a visual stimulus than to its onset. This is called the onset advantage. In the first of four experiments, we discovered that a spurious onset advantage can be produced by the long persistence of P31 phosphor. In the remaining three experiments, we found that offset RTs were slower only when they were made in a context in which responses to the abrupt onset of some stimuli had to be suppressed. We tested this hypothesis of response suppression in two ways: (1) by mixing regular onset trials with other trials on which a response to an onset had to be suppressed, and (2) by ramping the emergence of "offset" stimuli over time, so that offsets were the only abrupt events in the display. In both cases, we found that the onset advantage depended critically on whether the responses were made in a context of response suppression. We conclude that the onset advantage is mediated not by sensory factors such as visible persistence, but by response programming factors that are strongly affected by contextual events.

Competition for consciousness among visual events: the psychophysics of reentrant visual processes.

Advances in neuroscience implicate reentrant signaling as the predominant form of communication between brain areas. This principle was used in a series of masking experiments that defy explanation by feed-forward theories. The masking occurs when a brief display of target plus mask is continued with the mask alone. Two masking processes were found: an early process affected by physical factors such as adapting luminance and a later process affected by attentional factors such as set size. This later process is called masking by object substitution, because it occurs whenever there is a mismatch between the reentrant visual representation and the ongoing lower level activity. Iterative reentrant processing was formalized in a computational model that provides an excellent fit to the data. The model provides a more comprehensive account of all forms of visual masking than do the long-held feed-forward views based on inhibitory contour interactions.

Visual masking plays two roles in the attentional blink.

When two targets are displayed in rapid visual sequence and masked by trailing patterns, identification accuracy is nearly perfect for the first target but follows a U-shaped pattern over temporal lag for the second target. Three experiments examined the role of visual masking in this attentional blink. Experiment 1 compared integration and interruption masks for both targets. Although either mask was effective in producing the blink when applied to the first target, only the interruption mask was effective when applied to the second target. Experiment 2 showed that integration masking of the second target was ineffective over a wide range of accuracy levels. Combining the two forms of masking in Experiment 3 confirmed the dissociation: A combined mask and only a main effect on accuracy for the first target, whereas it produced a qualitatively different pattern over temporal lag for the second target. These results suggest that representations of the target are substituted in consciousness by that of the interruption mask when visual attention is preoccupied.

A possible selective impairment of magnocellular function in compression of the anterior visual pathways.

Two parallel visual systems, the magnocellular (M) and parvocellular (P) pathways, originate from different types of retinal ganglion cells, and are known to be segregated in different portions of the pregeniculate visual pathways. Their relative contribution to two main cortical streams, dorsal and ventral, is still under discussion, but it is reasonable to suppose that selective damage to the M or P subcortical system might interfere with specific aspects of processing within one or the other cortical system. Using two different apparent-motion tasks, we compared the performance of patients affected by compression of the ventral part of the pregeniculate visual pathways with that of normal controls. In the first task, observers detected small displacements of a low-contrast vertical bar, while in the second task they estimated the visible persistence of moving dots. In the first task, patients were impaired with parafoveal displays, especially in the temporal portion of the visual field. In the second task, patients showed reduced suppression of visible persistence at long, but not at short, exposure durations. Three considerations support the hypothesis that these results represent a selective impairment of the M system. First, M axons are more likely to suffer from compression, particularly in the case of a mass growing from below since they are known to occupy a ventral subpial position in the optic chiasm and tract. Second, the performance of patients with a ventral compression is consistent with the characteristics of the response properties of P ganglion cells, which have previously been shown to exhibit elevated and unmodulated thresholds for displacement detection in the macaque monkey. Third, such patients are less sensitive to the inhibitory signals that suppress visible persistence, which probably originate in the M system.

The attentional blink with targets in different spatial locations.

When two targets (T1 and T2) are displayed in rapid succession, accuracy of T2 identification varies as a function of the temporal lag between the targets (attentional blink, AB). In some studies, performance has been found to be most impaired at Lag 1--namely, when T2 followed T1 directly. In other studies, T2 performance at Lag 1 has been virtually unimpaired (Lag 1 sparing). In the present work, we examined how Lag 1 sparing is affected by attentional switches between targets displayed in the same location or in different locations. We found that Lag 1 sparing does not occur when a spatial shift is required between T1 and T2. This suggests that attention cannot be switched to a new location while the system is busy processing another stimulus. The results are explained by a modified version of an attentional gating model (Chun & Potter, 1995; Shapiro & Raymond, 1994).

Beyond the attentional blink: visual masking by object substitution.

If 2 targets are to be identified among distractors displayed in rapid sequence, correct identification of the 1st target hinders identification of the 2nd. To obtain this attentional blink (AB), the 1st target must be masked with a simultaneous (integration) or a delayed (interruption) mask indifferently. In 3 experiments, it was shown that the 2nd target must also be masked, but that the precise form of masking is important: An AB occurs with interruption but not with integration masking. This nonequivalence of masking paradigms parallels that found in studies of masked priming, a phenomenon arguably related to the AB. The results are explained by a revised 2-stage model (M. M. Chun & M. C. Potter, 1995).

Phosphor persistence of oscilloscopic displays: a comparison of four phosphors.

The period for which phosphor decay remains visible after stimulus offset was assessed for four phosphors commonly used in psychophysical experiments: P4, P15, P31, and P46. Stimuli were displayed behind closed shutters which opened at various intervals after stimulus offset. Thus, the observers' responses were based solely on the visibility of phosphor persistence. We varied viewing conditions (dark-adapted vs. veiling light), type of task (detection vs. identification), and intensity of the stimuli. No detectable persistence was ever produced by the P15 phosphor. In contrast, the P31 phosphor remained visible for several hundred ms. even with a veiling light. The P4 and P46 phosphors produced persistence of intermediate durations. It is concluded that P15 is the phosphor of choice for visual experiments.

Psychophysical evidence of a sustained input to directionally selective motion mechanisms.

Human psychophysical evidence congruent with neurophysiological findings of a sustained input to directionally selective motion sensors in cat visual cortex is reported. Apparent motion was produced by displaying a group of dots in two frames (F1 and F2), where F2 was a translated version of F1. All stimulus sequences included a period during which F1 and F2 were displayed concurrently (combined images) and a period during which only F1 or F2 was on display (single images). There were three stimulus sequences: a display beginning with combined and ending with single image, a display beginning with single and ending with combined image, and a display beginning with F1, continuing with combined image, and ending with F2. Six durations of single and of combined images (10, 20, 40, 80, 160, and 320 ms) were crossed factorially in each stimulus sequence. Directional motion was seen easily at long durations of the single image in all stimulus sequences, as would be expected on the basis of a sustained input to the directional-motion-sensing mechanisms. Perception of directional motion improved with the duration of single images, but declined as the duration of combined images was increased. Baker and Cynader's model could account for the effect of duration of single images, but not for the effect of duration of combined images. An elaborated version of the model provides a good qualitative match to all empirical findings.

Inverse-intensity effect in duration of visible persistence.

Duration of visible persistence can vary inversely with stimulus intensity. This inverse-intensity effect is obtained by varying the intensity of the stimuli or of the background, provided that the variations extend into the mesopic range. A similar relationship--known as the Ferry-Porter law--holds for the critical frequency at fusion (CFF). The authors propose that studies of CFF, 2-pulse threshold, and visible persistence can be encompassed within 1 conceptual framework in which the effect is modeled by the progressive reduction in the temporal extent of the positive phase of the system's response as the level of light adaptation changes from scotopic to photopic. In this context, the authors present an integrative scheme in which G. Sperling and M. M. Sondhi's (1968) formal model and M. Coltheart's (1980) neurophysiological conjecture are shown to be compatible and complementary accounts of the effect.

Motion and metacontrast with simultaneous onset of stimuli.

Coherent directional motion can be seen if an image is displayed in two sequential frames (F1 and F2), where F2 is a translated version of F1. A similar two-frame sequence can produce metacontrast masking: the visibility of a leading target (F1) is reduced by a trailing, spatially nonoverlapping mask (F2). Strict temporal succession of the stimuli has been considered essential for both motion and masking. This requirement for a minimum stimulus-onset asynchrony (SOA) is known as the SOA law. Contrary to the SOA law, we found that motion and masking can be obtained with simultaneous onsets of the stimuli, provided that F2 outlasts F1. We compared motion and metacontrast with simultaneous onsets of the stimuli (SIM paradigm) with the traditional paradigm in which an interstimulus interval (ISI) is inserted between the leading and the trailing stimuli (ISI paradigm). We studied the effects in light-adapted and in dark-adapted viewing, each over a wide range of stimulus intensities. Homologous results were obtained with the two paradigms, thus disconfirming the SOA law. Models of motion sensors, such as that proposed by Reichardt [in Sensory Communication, W. A. Rosenblith, ed. (MIT Press, Cambridge, Mass., 1961), p. 303], are inherently capable of explaining the motion results obtained with both paradigms. The masking results with the SIM paradigm disconfirm theories based on onset-locked slow excitatory and fast inhibitory responses but can be explained in terms of Bridgeman's network model [Bull. Math. Biol. 40, 605 (1978)]. In light of the results obtained with the two paradigms, we discuss, and tentatively support, the suggestion that motion and metacontrast may be complementary parts of a unitary perceptual system.

Temporal integration and segregation of brief visual stimuli: patterns of correlation in time.

Two brief sequential displays separated by a brief interstimulus interval (ISI) are often perceived as a temporally integrated unitary configuration. The probability of temporal integration can be decreased by increasing the ISI or (counterintuitively) by increasing stimulus duration. We tested three hypotheses of the relative contributions of stimulus duration and ISI to the breakdown of temporal integration (the storage, processing, and temporal correlation hypotheses). In the first of two experiments, stimulus duration and ISI were varied factorially, and estimates of temporal integration were obtained with a form-part integration task. The second experiment was a replication of the first at two levels of stimulus intensity. The outcomes were inconsistent with the storage and processing options, but confirmed predictions from the temporal correlation hypothesis. Whether two sequential stimuli are perceived as temporally integrated or disjoint depends not on the availability of visible persistence, but on the emergence of a neural code that is based on the temporal correlation between the two visual responses.

Beyond visible persistence: an alternative account of temporal integration and segregation in visual processing.

When processing sequences of rapidly varying stimuli, the visual system must satisfy two conflicting requirements. To maintain perceptual continuity, sequential stimuli must be integrated into a single, unified percept. On the other hand, to detect rapid changes, sequential stimuli must be segregated from each other. We propose that these conflicting demands are reconciled by a process that codes the temporal relationship between contiguous stimuli: Stimuli that are coded as co-extensive are integrated and those that are coded as disjoint are segregated. This approach represents a conceptual departure from the more traditional "intrinsic persistence" view of temporal integration. The approach provides a parsimonious account of the results of two temporal-integration tasks in which the durations of the leading and trailing displays were varied over a broad range. The data were accurately fit by a quantitative model in which temporal codes were determined by the correlation in time between the visual responses to the leading and trailing displays.

On the confounding effects of phosphor persistence in oscilloscopic displays.

Phosphor persistence has been a source of confounding in studies of temporal integration in vision. We examined the confounding by assessing the effects of the persistence of two commonly-used phosphors (P15 and P31) on performance of a temporal-integration task. In one experiment we eliminated the visibility of phosphor persistence by closing two mechanical shutters upon display termination. In a second experiment we estimated the duration of phosphor persistence by displaying the image behind closed shutters which opened upon display termination. No detectable persistence was every produced by P15 phosphor. By contrast, P31 phosphor produced persistence that lasted several hundred milliseconds even when a veiling light was projected on the screen. We ascribe the earlier instances of confounding to inadequate interpretation of the technical data on phosphor decay.