João P. Rodrigues

The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates.

Messenger RNAs are exported from the nucleus as large ribonucleoprotein complexes (mRNPs). To date, proteins implicated in this process include TAP/Mex67p and RAE1/Gle2p and are distinct from the nuclear transport receptors of the beta-related, Ran-binding protein family. Mex67p is essential for mRNA export in yeast. Its vertebrate homolog TAP has been implicated in the export of cellular mRNAs and of simian type D viral RNAs bearing the constitutive transport element (CTE). Here we show that TAP is predominantly localized in the nucleoplasm and at both the nucleoplasmic and cytoplasmic faces of the nuclear pore complex (NPC). TAP interacts with multiple components of the NPC including the nucleoporins CAN, Nup98, Nup153, p62, and with three major NPC subcomplexes. The nucleoporin-binding domain of TAP comprises residues 508-619. In HeLa cells, this domain is necessary and sufficient to target GFP-TAP fusions to the nuclear rim. Moreover, the isolated domain strongly competes multiple export pathways in vivo, probably by blocking binding sites on the NPC that are shared with other transport receptors. Microinjection experiments implicate this domain in the export of specific CTE-containing RNAs. Finally, we show that TAP interacts with transportin and with two proteins implicated in the export of cellular mRNAs: RAE1/hGle2 and E1B-AP5. The interaction of TAP with nucleoporins, its direct binding to the CTE RNA, and its association with two mRNP binding proteins suggest that TAP is an RNA export mediator that may bridge the interaction between specific RNP export substrates and the NPC.

Dbp5, a DEAD‐box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p

Dbp5 is a DEAD‐box protein essential for mRNA export from the nucleus in yeast. Here we report the isolation of a cDNA encoding human Dbp5 (hDbp5) which is 46% identical to yDbp5p. Like its yeast homologue, hDbp5 is localized within the cytoplasm and at the nuclear rim. By immunoelectron microscopy, the nuclear envelope‐bound fraction of Dbp5 has been localized to the cytoplasmic fibrils of the nuclear pore complex (NPC). Consistent with this localization, we show that both the human and yeast proteins directly interact with an N‐terminal region of the nucleoporins CAN/Nup159p. In a conditional yeast strain in which Nup159p is degraded when shifted to the nonpermissive temperature, yDbp5p dissociates from the NPC and localizes to the cytoplasm. Thus, Dbp5 is recruited to the NPC via a conserved interaction with CAN/Nup159p. To investigate its function, we generated defective hDbp5 mutants and analysed their effects in RNA export by microinjection in Xenopus oocytes. A mutant protein containing a Glu→Gln change in the conserved DEAD‐box inhibited the nuclear exit of mRNAs. Together, our data indicate that Dbp5 is a conserved RNA‐dependent ATPase which is recruited to the cytoplasmic fibrils of the NPC where it participates in the export of mRNAs out of the nucleus.

Vesicular Stomatitis Virus Matrix Protein Inhibits Host Cell Gene Expression by Targeting the Nucleoporin Nup98

Vesicular stomatitis virus matrix protein (VSV M) has been shown to inhibit both transcription and nucleocytoplasmic transport. We have isolated a mutant form of M, termed M(D), lacking both inhibitory activities. HeLa cells expressing M, but not M(D), accumulate polyadenylated RNAs within the nucleus. Concomitantly, a fraction of M, but not of the M(D) mutant, localizes at the nuclear rim. Additionally, the nucleoporin Nup98 specifically interacts with M but not with M(D). In Nup98(-/-) cells, both the levels of M at the nuclear envelope and its inhibitory effects on host cell-directed expression of reporter genes were significantly reduced. Together, our data demonstrate that VSV M inhibits host cell gene expression by targeting a nucleoporin and primarily blocking nuclear export.

TAP (NXF1) belongs to a multigene family of putative RNA export factors with a conserved modular architecture.

ABSTRACT Vertebrate TAP (also called NXF1) and its yeast orthologue, Mex67p, have been implicated in the export of mRNAs from the nucleus. The TAP protein includes a noncanonical RNP-type RNA binding domain, four leucine-rich repeats, an NTF2-like domain that allows heterodimerization with p15 (also called NXT1), and a ubiquitin-associated domain that mediates the interaction with nucleoporins. Here we show that TAP belongs to an evolutionarily conserved family of proteins that has more than one member in higher eukaryotes. Not only the overall domain organization but also residues important for p15 and nucleoporin interaction are conserved in most family members. We characterize two of four human TAP homologues and show that one of them, NXF2, binds RNA, localizes to the nuclear envelope, and exhibits RNA export activity. NXF3, which does not bind RNA or localize to the nuclear rim, has no RNA export activity. Database searches revealed that although only one p15(nxt) gene is present in the Drosophila melanogaster and Caenorhabditis elegans genomes, there is at least one additional p15 homologue (p15-2 [also called NXT2]) encoded by the human genome. Both human p15 homologues bind TAP, NXF2, and NXF3. Together, our results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity.

Individual alpha neurofeedback training effect on short term memory

Memory performance has been reported to be associated with electroencephalogram (EEG) alpha activity. This study aimed to improve short term memory performance by individual alpha neurofeedback training (NFT). With appropriate protocol designed for NFT, the experimental results showed that the participants were able to learn to increase the relative amplitude in individual alpha band during NFT and short term memory performance was significantly enhanced by 20 sessions of NFT. More importantly, further analysis revealed that the improvement of short term memory was positively correlated with the increase of the relative amplitude in the individual upper alpha band during training. In addition, effective strategies for individual alpha training varied among individuals and the most successful mental strategies were related to positive thinking.

EEG training platform: Improving Brain-Computer Interaction and cognitive skills

This work proposes a complete structure of an EEG biofeedback platform focused on an efficient way for its user to learn how to self regulate cortical activity. A longitudinal study of how voluntary training of specific electro cortical activity produces any stable changes in the electroencephalogram is also presented. Correlations of these changes with short term memory are also hypothesized. In this work the human brain was seen as an electrochemical machine capable of receiving stimuli and adapt accordingly. So, only relevant EEG activity was fed back to the trainee by a Brain Computer Interface (BCI) in an intelligible way, allowing the identification of phasic changes in the EEG and what cognitive state caused it. The results from this study showed that it is possible to learn to change some rhythmical activity in the EEG, in this case the alpha activity, after a few feedback sessions. A positive relation between this frequency band and cognitive processes was also observed. These results also indicate that the proposed EEG biofeedback protocol can be shaped as a tool for those who rely on BCI to communicate with the external world as it allows the tracking and training of individual frequency bands.

Neurofeedback for the treatment of schizophrenia: Case study

The paper presents a case report of the therapy by neurofeedback training of a chronic female schizophrenia outpatient. The purpose of the neurofeedback training was to enhance cognition, memory and behavioral performance. We used an intensive approach. All the training sessions were performed during 4 consecutive days. The results showed that the patient learnt to increase individual alpha amplitude and simultaneously decrease beta2 (20-30 Hz) amplitude at P4 site during active state over sessions. The individual alpha increased 74.73% and beta2 decreased 13.73%. The short term memory was enhanced after training. Her mood had positive change and her speech was much clearer than before. She started to associate the meaning of her life and illness. These results support that neurofeedback is not only a feasible therapy for schizophrenia but also positive results could be obtained using a much more intensive training sessions than the one reported in the literature.

Object recognition test in peripheral vision: a study on the influence of object color, pattern and shape

As an important factor for central vision preview, peripheral vision is a crucial ability for most ball game players in motion detection. A critical problem with peripheral vision is object recognition which has not yet been given much attention. This paper presents an experimental study to evaluate the influence on object recognition in peripheral vision due to different patterns, colors and shapes of the objects. More specifically, four types of shapes (including circles, triangles, horizontal stripes and vertical stripes) with various colors presented in different patterns were applied during the peripheral vision test. The results show that different patterns and colors indeed affect object recognition in peripheral vision in terms of accuracy and response time, while different types of shapes do not vary the performance significantly.

EEG Biofeedback: Viability and Future Directions

This chapter describes the structure of an EEG biofeedback platform focused on an efficient way for its user to learn how to self regulate cortical activity. A longitudinal study of how voluntary training of specific electro cortical activity produces any stable changes in the electroencephalogram is also presented. Correlations of these changes with short term memory are also hypothesized. The results from this study showed that it is possible to learn to change some rhythmical activity in the EEG, in this case the alpha activity, after a few feedback sessions. A positive relation between this frequency band and cognitive processes was also observed. A new technique based on the Hilbert Huang Transform is proposed for the analysis of EEG signals in biofeedback protocols. Initial observations of the results of this technique are presented.

Dream Therapy: Correlation of Dream Contents with Encephalographic and Cardiovascular Activations

Sleep and dreaming are overlapping and inseparable phenomena, but they have not often been addressed simultaneously in the scientific sleep research literature. This chapter describes dream research with a focus on objective dream content analysis and on neurocognitive theory analysis. Special emphasis is placed on connecting dream content analysis with current and advanced sleep research methodologies. This chapter presents some of the traditional and current interventions on dreaming during the periods of REM and NREM sleep, namely the behavioral and physical interventions. A more holistic view is provided through the description of the relationship of REM–NREM sleep and dreaming neurophysiology with the autonomous nervous system. A survey of current dream therapy usage is discussed in the light of the holistic approach provided, with the aim of showing pathways for future applications.