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Paolo Martini

Publications and source records attributed to Paolo Martini.

6 recordsLinked to original sources

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

Orientation tuning of human face processing estimated by contrast matching in transparency displays.

Upright images of faces appear more salient than faces of other orientations. We exploited this effect in a titration experiment where faces were superimposed in transparency. By manipulating the physical contrast of the component images, we measured the degree of perceptual dominance as function of the orientation of the face in the image plane. From these measurements, we obtain the orientation tuning of face processing, which is well approximated by a Gaussian function with a SD of about 45 deg and mean centered on upright. Faces predominantly lit from above and from below produced very similar results. However, when presented with scrambled faces observers showed no orientation preference. We argue that these results can be explained by the existence of specialized face processing mechanisms with an orientation tuning with a bandwidth of approximately 90 deg, predominantly centered on the upright orientation and easily disrupted by alterations of the normal facial configuration.

Contrast Sensitivity↗

Short-term memory for scenes with affective content.

The emotional content of visual images can be parameterized along two dimensions: valence (pleasantness) and arousal (intensity of emotion). In this study we ask how these distinct emotional dimensions affect the short-term memory of human observers viewing a rapid stream of images and trying to remember their content. We show that valence and arousal modulate short-term memory as independent factors. Arousal influences dramatically the average speed of data accumulation in memory: higher arousal results in faster accumulation. Valence has a more interesting effect: while a picture is being viewed, information from positive and neutral scenes accumulates in memory at a constant rate, whereas information from negative scenes is encoded slowly at first, then increasingly faster. We provide evidence showing that neither differences in low-level image properties nor differences in the ability to apprehend the meaning of images at short exposures can account for the observed results, and propose that the effects are specific to the short-term memory mechanism. We interpret this pattern of results to mean that information accumulation in short-term memory is a controlled process, whose gain is modulated by valence and arousal acting as endogenous attentional cues.

Adolescent↗

Implicit short-term memory and event frequency effects in visual search.

Numerous experiments have shown that animals and humans behave as if guided by an implicit knowledge of the relative frequency of occurrence of events in their environment. A well-known example of such trait is "Hick's Law" for reaction times: responses to more frequent stimuli are faster than to less frequent ones. In the present study, we demonstrate that an important source of the effects produced by Hick's law in the context of a visual search task is to be found in a form of implicit short-term memory, previously described as Priming of Pop-out. We report the results of experiments in which we have disrupted or enhanced the accumulation of implicit short-lived memory traces in the context of visual search tasks where stimulus frequency was varied. With target frequencies greater than 20%, these memory manipulations resulted in the elimination or enhancement of the effect of stimulus frequency on reaction times, thus indicating that an implicit, finite-memory accumulator is an important underlying mechanism for frequency effects in visual search paradigms. We characterize the properties of the accumulator and discuss the kinds of behaviors in which it may be implicated.

Color Perception↗

Type V phosphodiesterase inhibitor treatments for erectile dysfunction increase testosterone levels.

OBJECTIVE: Lack of sexual activity due to erectile dysfunction (ED) decreases testosterone (T) levels through a central effect on the hypothalamic-pituitary axis. In this paper we studied the effect of different type V phosphodiesterase (PDE5) inhibitor treatments for ED on the reversibility of this endocrine pattern. DESIGN: Open-label, retrospective study. PATIENTS: Seventy-four consecutive patients were treated on demand with sildenafil (Sild) (50 mg) and tadalafil (Tad) 20 mg. MEASUREMENTS: The success in sexual intercourse was recorded and total (tT) and free testosterone (fT) levels were studied before and after 3 months of treatment. RESULTS: Basal level of tT and fT were at the bottom of the normal range and LH levels were at the top of the high normal range. After treatments, this endocrine pattern was reversed in both groups. However, the T increase in Sild-treated patients was significantly lower than in those treated with Tad (4.7 +/- 2.7 vs. 5.1 +/- 0.9, P < 0.001). fT levels followed a directly proportional pattern, while the inverse was found when LH production was studied. The intercourse rate reflected this effect: in fact, the Sild group showed a 4.9 +/- 2.9/month full sexual intercourse rate while in the Tad group a significantly higher rate of sexual intercourse was found (6.9 +/- 4.6/month, P = 0.04). However, drug consumption was comparable between the groups (Sild 4.9 +/- 2.9 vs. Tad 4.4 +/- 2.8 pills/month, P = 0.72). CONCLUSIONS: As it is unlikely that the two drugs have a different direct effect on the pituitary-testis axis, this effect is probably due to the higher frequency of full sexual intercourse in the Tad-treated group, because of the drug's longer half-life.

3',5'-Cyclic-GMP Phosphodiesterases↗

Bilateral deficits of transient visual attention in right parietal patients.

Vision tells us not only what and where objects are but also when they appear and disappear. We have found that patients with right parietal damage have an unusual loss in the ability to differentiate object onset from offset. Specifically, when a single target flickers at the same frequency as five distractors, but out of phase (it is light when they are dark and vice versa), right parietal patients require much slower rates than normals or left parietal patients to detect the target. When we shifted the phase of the flicker in the target relative to the distractors so that the onsets and offsets were not simultaneous, the performance of the patients improved dramatically. Remarkably, the patients showed this loss equally in both visual fields. Since flicker detection was normal for the patients, we suggest that the deficit lies at a level where stimulus transients are interpreted as the appearance or disappearance of objects.

Attention↗