ORCID Profile
0000-0002-7361-0980
Current Organisations
Virginia Polytechnic Institute and State University
,
Trinity College Dublin
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-03-2012
DOI: 10.1126/SCITRANSLMED.3003016
Abstract: A novel compound, Imipramine Blue, enhances efficacy of chemotherapy in a single treatment against a rodent astrocytoma model in vivo by inhibiting cell invasion.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2010
DOI: 10.1158/1538-7445.AM10-3702
Abstract: Statement of Purpose: Due to their invasive nature, malignant gliomas are difficult neoplasms to treat leading to poor prognosis. Invasive gliomas therefore elude current treatment involving chemotherapy, surgical resection and radiation. Additionally, anti-angiogenic therapy often enhances invasion and current ‘anti-invasive’ agents fail clinically. Here, we identify a new anti-invasive compound and target it therapeutically to invasive brain tumors. Methods: Twenty-four small molecule compounds designed to have novel anti-tumor effects via NADPH oxidase inhibition were screened for anti-invasive properties against the rat glioma model RT2 using modified Boyden chamber assay. One compound, Imipramine Blue(IB), was identified to be anti-invasive but not cytotoxic. IB was encapsulated using liposomes (Nano-IB) to improve its pharmacokinetics and increase its preferential accumulation in brain tumors. Rats inoculated with RT2 invasive glioma were treated with either saline or nano-IB (3mg/kg total) on day 4 and 7 after orthotopic tumor inoculation, and sacrificed via intracardial perfusion on day 11. One set of animals was prepared for histological examination and another for and RNA (n=3 per group) and protein (n=3 per group) harvest. Microarray analysis was performed using the Affymetrix 230 2.0 system at Morehouse School of Medicine (Atlanta, GA) and analyzed using Genespring and Ingenuity Pathway Analysis (IPA). Confirmatory quantitative rt-PCR and Western blotting were performed for genes of interest. Results: When delivered in vivo, Nano-IB halted invasion as determined by analyzing tumor borders on day 11 by imaging analysis. Microarray analysis indicated greater than 2-fold change in approximately 60 genes including, a subset of genes involved in the regulation of actin polymerization: scinderin, profilin-1, calgranulin, α-actin, and rhoGTPase inhibitor A. Confirmatory rt-PCR using pooled RNA s les and western blotting confirmed the differences seen in microarray. Using IPA, several upstream candidate target molecules were identified which may be acting to cause the downstream effects including PI3K, PKC, and MAPK/ERK. Further, using IB in vitro showed dramatic effects on the actin cytoskeleton in the RT2 cells. Conclusions: Imipramine Blue, a novel small molecule therapeutic, effectively halts invasion of the RT2 astrocytoma cell line in vitro and in vivo as evidenced by Boyden chamber assay and histological examination brain inoculated with invasive RT-2 tumors. Furthermore, the drug is acting via alteration of the actin cytoskeleton as shown in vitro by cytological examination and in vivo through microarray and western blotting analysis. However, due to number of genes that are affected upon treatment the drug is not directly acting on actin filaments in the cell but rather on an upstream regulator of actin polymerization regulating molecules. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research 2010 Apr 17-21 Washington, DC. Philadelphia (PA): AACR Cancer Res 2010 (8 Suppl):Abstract nr 3702.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.NEUROIMAGE.2022.119217
Abstract: An auditory-visual speech benefit, the benefit that visual speech cues bring to auditory speech perception, is experienced from early on in infancy and continues to be experienced to an increasing degree with age. While there is both behavioural and neurophysiological evidence for children and adults, only behavioural evidence exists for infants - as no neurophysiological study has provided a comprehensive examination of the auditory-visual speech benefit in infants. It is also surprising that most studies on auditory-visual speech benefit do not concurrently report looking behaviour especially since the auditory-visual speech benefit rests on the assumption that listeners attend to a speaker's talking face and that there are meaningful in idual differences in looking behaviour. To address these gaps, we simultaneously recorded electroencephalographic (EEG) and eye-tracking data of 5-month-olds, 4-year-olds and adults as they were presented with a speaker in auditory-only (AO), visual-only (VO), and auditory-visual (AV) modes. Cortical tracking analyses that involved forward encoding models of the speech envelope revealed that there was an auditory-visual speech benefit [i.e., AV > (A + V)], evident in 5-month-olds and adults but not 4-year-olds. Examination of cortical tracking accuracy in relation to looking behaviour, showed that infants' relative attention to the speaker's mouth (vs. eyes) was positively correlated with cortical tracking accuracy of VO speech, whereas adults' attention to the display overall was negatively correlated with cortical tracking accuracy of VO speech. This study provides the first neurophysiological evidence of auditory-visual speech benefit in infants and our results suggest ways in which current models of speech processing can be fine-tuned.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2018
DOI: 10.1038/S41598-018-32150-6
Abstract: This study assessed cortical tracking of temporal information in incoming natural speech in seven-month-old infants. Cortical tracking refers to the process by which neural activity follows the dynamic patterns of the speech input. In adults, it has been shown to involve attentional mechanisms and to facilitate effective speech encoding. However, in infants, cortical tracking or its effects on speech processing have not been investigated. This study measured cortical tracking of speech in infants and, given the involvement of attentional mechanisms in this process, cortical tracking of both infant-directed speech (IDS), which is highly attractive to infants, and the less captivating adult-directed speech (ADS), were compared. IDS is the speech register parents use when addressing young infants. In comparison to ADS, it is characterised by several acoustic qualities that capture infants’ attention to linguistic input and assist language learning. Seven-month-old infants’ cortical responses were recorded via electroencephalography as they listened to IDS or ADS recordings. Results showed stronger low-frequency cortical tracking of the speech envelope in IDS than in ADS. This suggests that IDS has a privileged status in facilitating successful cortical tracking of incoming speech which may, in turn, augment infants’ early speech processing and even later language development.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.NEUROIMAGE.2018.03.072
Abstract: Developmental dyslexia is a multifaceted disorder of learning primarily manifested by difficulties in reading, spelling, and phonological processing. Neural studies suggest that phonological difficulties may reflect impairments in fundamental cortical oscillatory mechanisms. Here we examine cortical mechanisms in children (6-12 years of age) with or without dyslexia (utilising both age- and reading-level-matched controls) using electroencephalography (EEG). EEG data were recorded as participants listened to an audio-story. Novel electrophysiological measures of phonemic processing were derived by quantifying how well the EEG responses tracked phonetic features of speech. Our results provide, for the first time, evidence for impaired low-frequency cortical tracking to phonetic features during natural speech perception in dyslexia. Atypical phonological tracking was focused on the right hemisphere, and correlated with traditional psychometric measures of phonological skills used in diagnostic dyslexia assessments. Accordingly, the novel indices developed here may provide objective metrics to investigate language development and language impairment across languages.
Location: United States of America
No related grants have been discovered for Giovanni Di Liberto.