Trial-by-trial changes in a priori informational value of external cues and subjective expectancies in human auditory attention

Background

Preparatory activity based on a priori probabilities generated in previous trials and subjective expectancies would produce an attentional bias. However, preparation can be correct (valid) or incorrect (invalid) depending on the actual target stimulus. The alternation effect refers to the subjective expectancy that a target will not be repeated in the same position, causing RTs to increase if the target location is repeated. The present experiment, using the Posner''s central cue paradigm, tries to demonstrate that not only the credibility of the cue, but also the expectancy about the next position of the target are changedin a trial by trial basis. Sequences of trials were analyzed.

Results

The results indicated an increase in RT benefits when sequences of two and three valid trials occurred. The analysis of errors indicated an increase in anticipatory behavior which grows as the number of valid trials is increased. On the other hand, there was also an RT benefit when a trial was preceded by trials in which the position of the target changed with respect to the current trial (alternation effect). Sequences of two alternations or two repetitions were faster than sequences of trials in which a pattern of repetition or alternation is broken.

Conclusions

Taken together, these results suggest that in Posner''s central cue paradigm, and with regard to the anticipatory activity, the credibility of the external cue and of the endogenously anticipated patterns of target location are constantly updated. The results suggest that Bayesian rules are operating in the generation of anticipatory activity as a function of the previous trial''s outcome, but also on biases or prior beliefs like the “gambler fallacy”.     

Targeting EDEM protects against ER stress and improves development and survival in C. elegans

EDEM-1, EDEM-2 and EDEM-3 are key players for the quality control of newly synthesized proteins in the endoplasmic reticulum (ER) by accelerating disposal and degradation of misfolded proteins through ER Associated Degradation (ERAD). Although many previous studies reported the role of individual ERAD components especially in cell-based systems, still little is known about the consequences of ERAD dysfunction under physiological and ER stress conditions in the context of a multicellular organism. Here we report the first individual and combined characterization and functional interplay of EDEM proteins in Caenorhabditis elegans using single, double, and triple mutant combinations. We found that EDEM-2 has a major role in the clearance of misfolded proteins from ER under physiological conditions, whereas EDEM-1 and EDEM-3 roles become prominent under acute ER stress. In contrast to SEL-1 loss, the loss of EDEMs in an intact organism induces only a modest ER stress under physiological conditions. In addition, chronic impairment of EDEM functioning attenuated both XBP-1 activation and up-regulation of the stress chaperone GRP78/BiP, in response to acute ER stress. We also show that pre-conditioning to EDEM loss in acute ER stress restores ER homeostasis and promotes survival by activating ER hormesis. We propose a novel role for EDEM in fine-tuning the ER stress responsiveness that affects ER homeostasis and survival.     

Structural basis of the lisinopril-binding specificity in N- and C-domains of human somatic ACE

Angiotensin I-converting enzyme (ACE) is a dipeptidyl carboxypeptidase which converts angiotensin I into the vasopressor peptide angiotensin II and also inactivates the hypotensive peptide bradykinin, playing an important role in blood pressure regulation. The present work describes the molecular modeling of the N-terminal human somatic ACE in complex with the inhibitor lisinopril, identifying the residues involved in the inhibitor-binding pocket. The obtained results identify differences in the lisinopril lysine moiety-binding residues for N- and C-terminals of sACE domains and an important carboxy-terminal proline hydrophobic accommodations mediated by the aromatic ring of Tyr532 and Tyr1128 residues, respectively. The present model will be useful for the development of a new inhibitor family based on the natural BPP peptides and derivatives, or even to improve the binding capacities and the domain specificity of the already known inhibitors.     

Anti-inflammatory and redox-protective activities of citronellal

The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.     

Solution structure of reduced Clostridium pasteurianum rubredoxin

The solution structure of reduced Clostridium pasteurianum rubredoxin (MW 6100) is reported here. The protein is highly paramagnetic, with iron(II) being in the S=2 spin state. The Hβ protons of the ligating cysteines are barely observed, and not specifically assigned. Seventy-six percent of the protons have been assigned and 1267 NOESY peaks (of which 1037 are meaningful) have been observed. Nonselective T ₁ measurements have been measured by recording four nonselective 180°-τ-NOESY at different τ values, and fitting the intensity recoveries to an exponential recovery. Thirty-six metal-proton upper and lower distance constraints have been obtained from the above measurements. The use of such constraints is assessed with respect to spin delocalization on the sulfur donor atoms. The solution structure obtained with the program DYANA has been refined through restrained energy minimization. A final family of 20 conformers is obtained with no distance violations larger than 0.24?Å, and RMSD values to the mean structure of 0.58 and 1.03?Å for backbone and all heavy atoms, respectively (measured on residues 3–53). The structure is compared to the X-ray structure of the oxidized and of the zinc substituted protein, and to the available structures of other rubredoxins. In particular, the comparison with the crystal structure and the solution structure of the Zn derivative of the highly thermostable Pyrococcus furiosus rubredoxin suggested that the relatively low thermal stability of the clostridial rubredoxin may be tentatively ascribed to the loosening of its secondary structure elements. This research is a further achievement at the frontier of solution structure determinations of paramagnetic proteins.     

Pathogen-derived resistance to Citrus tristeza virus (CTV) in transgenic mexican lime (Citrus aurantifolia (Christ.) Swing.) plants expressing its p25 coat protein gene

The p25 coat protein (CP) gene of Citrustristezavirus (CTV) was incorporated to Mexican lime plants and forty-twotransgeniclines were produced, 25 containing the p25 CP gene of thesevere CTV strain T-305 and 17 with that of the mild strain T-317. When plantspropagated from each transgenic line were graft-inoculated with CTV T-305 oraphidinoculated with T-300, two types of response to viral challenge wereobserved: some lines developed CTV symptoms similar to those of non-transgeniccontrols, whereas others exhibited protection against the virus. Thisprotectionconsisted of a proportion of plants, ranging from 10 to 33%, that wereresistantto CTV, and the rest of them that showed a significant delay in virusaccumulation and symptom onset. Protection was efficient against non-homologousCTV strains and was generally accompanied by high accumulation of p25 CP in theprotected lines, which suggest a CP-mediated protection mechanism in mostcases.This is the first report demonstrating pathogen-derived resistance intransgenicplants against a Closterovirus member in its natural host.     

Changes in native and introduced host–parasite networks

Biological Invasions - Introduced species can alter the dynamics and structure of a native community. Network analysis provides a tool to study host–parasite interactions that can help to...     

Differential Denaturation of Serum Proteome Reveals a Significant Amount of Hidden Information in Complex Mixtures of Proteins

Recently developed proteomic technologies allow to profile thousands of proteins within a high-throughput approach towards biomarker discovery, although results are not as satisfactory as expected. In the present study we demonstrate that serum proteome denaturation is a key underestimated feature; in fact, a new differential denaturation protocol better discriminates serum proteins according to their electrophoretic mobility as compared to single-denaturation protocols. Sixty nine different denaturation treatments were tested and the 3 most discriminating ones were selected (TRIDENT analysis) and applied to human sera, showing a significant improvement of serum protein discrimination as confirmed by MALDI-TOF/MS and LC-MS/MS identification, depending on the type of denaturation applied. Thereafter sera from mice and patients carrying cutaneous melanoma were analyzed through TRIDENT. Nine and 8 protein bands were found differentially expressed in mice and human melanoma sera, compared to healthy controls (p<0.05); three of them were found, for the first time, significantly modulated: α2macroglobulin (down-regulated in melanoma, p<0.001), Apolipoprotein-E and Apolipoprotein-A1 (both up-regulated in melanoma, p<0.04), both in mice and humans. The modulation was confirmed by immunological methods. Other less abundant proteins (e.g. gelsolin) were found significantly modulated (p<0.05).Conclusions: i) serum proteome contains a large amount of information, still neglected, related to proteins folding; ii) a careful serum denaturation may significantly improve analytical procedures involving complex protein mixtures; iii) serum differential denaturation protocol highlights interesting proteomic differences between cancer and healthy sera.     

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.