Temporal order processing of syllables in the left parietal lobe

Speech processing requires the temporal parsing of syllable order. Individuals suffering from posterior left hemisphere brain injury often exhibit temporal processing deficits as well as language deficits. Although the right posterior inferior parietal lobe has been implicated in temporal order judgments (TOJs) of visual information, there is limited evidence to support the role of the left inferior parietal lobe (IPL) in processing syllable order. The purpose of this study was to examine whether the left inferior parietal lobe is recruited during temporal order judgments of speech stimuli. Functional magnetic resonance imaging data were collected on 14 normal participants while they completed the following forced-choice tasks: (1) syllable order of multisyllabic pseudowords, (2) syllable identification of single syllables, and (3) gender identification of both multisyllabic and monosyllabic speech stimuli. Results revealed increased neural recruitment in the left inferior parietal lobe when participants made judgments about syllable order compared with both syllable identification and gender identification. These findings suggest that the left inferior parietal lobe plays an important role in processing syllable order and support the hypothesized role of this region as an interface between auditory speech and the articulatory code. Furthermore, a breakdown in this interface may explain some components of the speech deficits observed after posterior damage to the left hemisphere

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers

This work was partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union – European Social Fund (ESF) under Operational Programme II – Cohesion Policy 2007-2013, “Empowering People for More Jobs and a Better Quality of Life”. This project was additionally funded by Medical Research Scotland.Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.Publisher PDFPeer reviewe

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Cortical mapping of naming errors in aphasia

Persons with aphasia vary greatly with regard to clinical profile; yet, they all share one common feature—anomia—an impairment in naming common objects. Previous research has demonstrated that particular naming errors are associated with specific left hemisphere lesions. However, we know very little about the cortical activity in the preserved brain areas that is associated with aphasic speech errors. Utilizing functional magnetic resonance imaging (fMRI), we show for the first time that specific speech errors are associated with common cortical activity in different types and severities of aphasia. Specifically, productions of phonemic errors recruited the left posterior perilesional occipital and temporal lobe areas. A similar pattern of activity was associated with semantic errors, albeit in the right hemisphere. This study does not discount variability in cortical activity following left hemisphere stroke; rather, it highlights commonalities in brain modulation in a population of patients with a common diagnosis but vastly different clinical profiles. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc

Sentence comprehension and general working memory

Although the role of working memory in sentence comprehension has received substantial attention, the nature of this relationship remains unclear. The purpose of this study was to examine the interaction between general, nonverbal working memory (WM) and sentence parsing (SP) in normal English‐speaking adults. Accuracy and reaction times were recorded for thirty‐one young adults during three on‐line tasks: nonverbal WM, SP plausibility, and lexical decision (LD). A significant positive correlation was observed between reaction times for WM and SP, but not between LD and SP. These results suggest that SP may be supported by a general WM capacity, and therefore, some sentence comprehension difficulties observed in the clinical population may potentially be related to impairment in general WM

Evidence for the Solidarity of the Expressive and Receptive Language Systems: A Retrospective Study

A strong tendency toward left hemisphere (LH) language dominance has been well established, as evidenced by the high prevalence of language impairment following sudden onset lesions in the LH. In the presence of progressive LH pathology, such as epilepsy, substantial deviations in language organization can occur. However, the question regarding whether reorganization involves both expressive and receptive language functions or only the one directly affected by the primary location of pathology has not been settled. Using Wada testing scores from 296 epilepsy patients and estimated rates of typical dominance in the normal population, we assessed the frequency with which left frontal and temporal pathology resulted in reorganization of only the expressive or receptive language function or both. The comparisons revealed: (1) a significantly higher prevalence of atypical organization (i.e., deviations from LH dominance) among the LH patients compared to normal population estimates and right hemisphere patients, and (2) that regardless of pathology location within the LH, the rates of atypical reorganization for both expressive and receptive language were essentially equal. These results constitute evidence that the two language functions are intimately yoked and that when disruption to the system results in reorganization, it usually yields functional changes throughout the system. (JINS, 2010, 17, 000–000