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Paul Ferrari

Publications and source records attributed to Paul Ferrari.

15 recordsLinked to original sources
PubMed2005

Human magnetoencephalographic evidence of early syntactic responses to c-selection violations of English infinitives and gerunds by L1 and L2 speakers.

Previous studies of syntactic processing in first-language (L1) speakers revealed an early syntactic component peaking at around 150 ms after phrase-structure (PS), c(categorical)-selection violations in German and English using magnetoencephalography (MEG) and event-related potentials, as well as non-PS violations in English using MEG. The current MEG study examined whether such an early component would apply to English c-selection (PS) violations and whether it would be observed in both L1 speakers and second-language (L2) learners. Five American L1 adults and five Japanese advanced L2 learners listened to grammatical and ungrammatical versions of two structures with infinitive (I) and gerund (G) complements, while MEG responses were recorded with a dual 37-channel gradiometer system. A prominent syntactic magnetic field component peaking at approximately 150 ms (so called "SF-M150") was generated by the incorrect *G condition (e.g., He happened using it). Such a prominent component was not observed in any other condition (e.g., the incorrect *I: He postponed to use it) for either group. L2 learners may possess automatic neuronal mechanisms comparable to L1 speakers for syntactic processing of infinitive c-selection violations.

Adult↗
PubMed2005

The elicitation of phonological and semantic neuromagnetic field components by non-words in human auditory sentence comprehension.

The current research examined whether neuromagnetic field components relating to pre-lexical and semantic analysis would be evoked by non-word violations in Japanese auditory sentence comprehension. Stimuli contained semantically congruent short vowel-duration words, long vowel-duration non-words, and short-duration non-words with a deviant second syllable. Native speakers listened to sentences, while neuromagnetic fields were recorded with a twin 37-channel gradiometer system. The results in the 200-400 ms time window showed that at a peak latency of approximately 300 ms, vowel-lengthening and deviant-syllable violations produced larger magnetic fields than congruent words. In the 450-600 ms time range, the magnetic fields in response to deviant-syllable violations, but not vowel-lengthening violations, were larger than congruent words, with the peak latency at approximately 500 ms. The elicitations of M300 and M500 components in this study support the biphasic hypothesis where a pre-lexical phonological analysis stage precedes a post-lexical semantic integration stage in lexical recognition of a native language.

Acoustic Stimulation↗
PubMed2004

UMP kinase from Streptococcus pneumoniae: evidence for co-operative ATP binding and allosteric regulation.

UMP kinase catalyses the phosphorylation of UMP by ATP to yield UDP and ADP. In prokaryotes, the reaction is carried out by a hexameric enzyme, activated by GTP and inhibited by UTP. In the present study, Streptococcus pneumoniae UMP kinase was studied as a target for antibacterial research and its interest was confirmed by the demonstration of the essentiality of the gene for cell growth. In the presence of MnCl2 or MgCl2, the saturation kinetics of recombinant purified UMP kinase was hyperbolic for UMP (K(m)=0.1 mM) and sigmoidal for ATP (the substrate concentration at half-saturation S0.5=9.4+/-0.7 mM and n=1.9+/-0.1 in the presence of MgCl2). GTP increased the affinity for ATP and decreased the Hill coefficient (n). UTP decreased the affinity for ATP and only slightly increased the Hill coefficient. The kcat (175+/-13 s(-1) in the presence of MgCl2) was not affected by the addition of GTP or UTP, whose binding site was shown to be different from the active site. The hydrodynamic radius of the protein similarly decreased in the presence of ATP or GTP. There was a shift in the pH dependence of the activity when the ATP concentration was switched from low to high. These results support the hypothesis of an allosteric transition from a conformation with low affinity for ATP to a form with high affinity, which would be induced by the presence of ATP or GTP.

Adenosine Diphosphate↗
PubMed2004

Human neuronal encoding of English syntactic violations as revealed by both L1 and L2 speakers.

Our previous study [M. Kubota, P. Ferrari, T.P.L. Roberts, Magnetoencephalography detection of early syntactic processes in humans: comparison between L1 speakers and L2 learners, Neurosci. Lett. 353 (2003) 107-110] showed that an early syntactic response was elicited in first language (L1) speakers for within-phrase, but not across-phrase violations, implying that there may exist a continuum of neuronal error gravity. Such an early component was not elicited by second-language (L2) learners. The current auditory study investigated whether two types of different syntactic violations regarding noun-phrase raising (NP-raising) and case-filter constructions would elicit a prominent early syntactic component in each hemisphere for both L1 and advanced L2 speakers of English. Neuromagnetic fields were recorded, using a dual 37-channel gradiometer system. A prominent component, peaking at approximately 150 ms post-onset, was observed in both hemispheres of two groups in response to NP-raising induced violations, but not case-filter violations. The findings imply that L1 and L2 speakers have similar neuronal mechanisms subserving syntactic processing of such violations.

Adult↗
PubMed2004

Prominence of M50 auditory evoked response over M100 in childhood and autism.

This study investigated the 50 ms (M50) and 100 ms (M100) components of the auditory evoked field to explore their change during development. Using MEG, neuromagnetic fields elicited by a 1 kHz sinusoidal tone were recorded in adults and two groups of children and adolescents with typical development or autism spectrum disorder. M50 amplitude was larger in children than in adults, suggesting a developmental trajectory with M50 amplitude decreasing and M100 increasing with age. Child M50 and M100 latencies were prolonged relative to adults. Children with autism did not differ from control children with respect to these observations. The M50 in relation to the M100 is a robust index of early auditory system maturation suitable for future developmental investigations.

Acoustic Stimulation↗
PubMed2004

Inhibitors of Civ1 kinase belonging to 6-aminoaromatic-2-cyclohexyldiamino purine series as potent anti-fungal compounds.

There is today a blatant need for new antifungal agents, because of the recent increase in life-threatening infections involving an ever-greater number of fungal strains. Fungi make extensive use of kinases in the regulation of essential processes, in particular the cell cycle. Most fungal kinases, however, are shared with higher eukaryotes. Only the kinases which have no human homologs, such as the histidine kinases, can be used as targets for antifungal drugs design. This review describes efforts directed towards the discovery of drugs active against a novel target, the atypical cell cycle kinase, Civ1.

Amino Acid Sequence↗
PubMed2004

Fluorescence detection-based functional assay for high-throughput screening for MraY.

We have developed a novel assay specific to MraY, which catalyzes the first membrane step in the biosynthesis of bacterial cell wall peptidoglycan. This was accomplished by using UDP-MurNAc-N(epsilon)-dansylpentapeptide, a fluorescent derivative of the MraY nucleotide substrate, and a partially purified preparation of MraY solubilized from membranes of an Escherichia coli overproducing strain. Two versions of the assay were developed, one consisting of the high-pressure liquid chromatography separation of the substrate and product (dansylated lipid I) and the other, without separation and adapted to the high-throughput format, taking advantage of the different fluorescence properties of the nucleotide and lipid I in the reaction medium. The latter assay was validated with a set of natural and synthetic MraY inhibitors.

Anti-Bacterial Agents↗
PubMed2003

Magnetic mismatch fields elicited by vowel duration and pitch changes in Japanese words in humans: comparison between native- and non-speakers of Japanese.

Previous event-related brain potential research showed that mismatch negativity was elicited by phoneme contrasts in fluent second language (L2) learners, but not in non-speakers of L2. The present study tested whether the magnetic mismatch field (MMF) would be elicited in response to temporal and spectral changes in three Japanese synthesized words for both native- and non-speakers of Japanese. Magnetoencephalography responses were recorded with a dual 37-channel gradiometer. Unlike short-to-long vowel duration and falling-to-level pitch changes, long-to-short duration and level-to-falling pitch changes elicited a prominent MMF bilaterally for both groups, peaking at around 100 ms after change onset for duration and 200 ms for pitch. The MMF component is sensitive to vowel shortening rather than lengthening and to pitch falling rather than leveling. Automatic detection of changes in vowel shortening and pitch falling is a useful index of language-non-specific auditory memory traces.

Acoustic Stimulation↗
PubMed2003

Magnetoencephalography detection of early syntactic processing in humans: comparison between L1 speakers and L2 learners of English.

In previous brain imaging studies of human syntax processing, only phrase structure (grammatical category) violations have been shown to elicit a very early (approximately 140 ms) neural response. This has led to interpretations about the nature of phrase structure encoding in the brain, particularly its relationship to early automatic brain processes. Utilizing different sentence structures that contrasted within- vs. across-phrase violations, the current study examined whether an early response could be elicited by non-phrase-structure violations. Magnetoencephalography fields were recorded, while both first-language speakers (L1) and second-language learners (L2) were tested. A prominent syntactic magnetic field component, peaking at around 150 ms post-onset (labeled 'SF-M150'), was observed in both hemispheres of only the L1 speakers in response to within-phrase violations but not across-phrase violations. The results provide evidence that L1 speakers possess the ability for automated detection of non-phrase-structure violations, particularly within-phrase violations, and that L2 learners may not have sufficient neural representation available for an early automated response to the target violations.

Adult↗
PubMed2003

The Mtr2-Mex67 NTF2-like domain complex. Structural insights into a dual role of Mtr2 for yeast nuclear export.

The formation of the Mtr2-Mex67 heterodimer is essential for yeast mRNA export as it constitutes a key nuclear component for shuttling mRNA between the nuclear and cytoplasm compartments through the nuclear pore complex. We report the crystal structures of apo-Mtr2 from the human pathogen Candida albicans and of its complex with the Mex67 NTF2-like domain. Compared with other members of the NTF2 fold family, Mtr2 displays novel structural features involved in the nuclear export of the large ribosomal subunit and consistent with a dual functional role of Mtr2 during yeast nuclear export events. The structure of the Mtr2-Mex67 NTF2-like domain complex, which overall is similar to those of the human and Saccharomyces cerevisiae homologs, unveils three putative Phe-Gly repeat binding sites, of which one contributes to the heterodimer interface. These structures exemplify an unrecognized adaptability of the NTF2 building block in evolution, identify novel structural determinants associated with key biological functions at the molecular surface of the yeast Mtr2-Mex67 complex, and suggest that the yeast and human mRNA export machineries may differ.

Active Transport, Cell Nucleus↗
PubMed2003

Preoperative magnetic source imaging for brain tumor surgery: a quantitative comparison with intraoperative sensory and motor mapping.

OBJECT: The aim of this study was to compare quantitatively the methods of preoperative magnetic source (MS) imaging and intraoperative electrophysiological cortical mapping (ECM) in the localization of sensorimotor cortex in patients with intraaxial brain tumors. METHODS: Preoperative magnetoencephalography (MEG) was performed while patients received painless tactile somatosensory stimulation of the lip, hand, and foot. The early somatosensory evoked field was modeled using a single equivalent current dipole approach to estimate the spatial source of the response. Three-dimensional magnetic resonance image volume data sets with fiducials were coregistered with the MEG recordings to form the MS image. These individualized functional brain maps were integrated into a neuronavigation system. Intraoperative mapping of somatosensory and/or motor cortex was performed and sites were compared. In two subgroups of patients we compared intraoperative somatosensory and motor stimulation sites with MS imaging-based somatosensory localizations. Mediolateral projection of the MS imaging source localizations to the cortical surface reduced systematic intermodality discrepancies. The distance between two corresponding points determined using MS imaging and ECM was 12.5 +/- 1.3 mm for somatosensory-somatosensory and 19 +/- 1.3 mm for somatosensory-motor comparisons. The observed 6.5 mm increase in site separation was systematically demonstrated in the anteroposterior direction, as expected from actual anatomy. In fact, intraoperative sites at which stimulation evoked the same patient response exhibited a spatial variation of 10.7 +/- 0.7 mm. CONCLUSIONS: Preoperative MS imaging and intraoperative ECM show a favorable degree of quantitative correlation. Thus, MS imaging can be considered a valuable and accurate planning adjunct in the treatment of patients with intraaxial brain tumors.

Adolescent↗
PubMed2003

Consistency of interictal and ictal onset localization using magnetoencephalography in patients with partial epilepsy.

OBJECT: The aim of this study was to evaluate the spatial accuracy of interictal magnetoencephalography (MEG) in localizing the primary epileptogenic focus in comparison with alternative MEG-derived estimates such as ictal onset recording or sensory mapping of the periphery where seizures manifest. METHODS: During this retrospective study of 12 patients with epilepsy who had undergone successful magnetic source (MS) imaging with the aid of a dual 37-channel biomagnetometer as well as simultaneous MEG/electroencephalography (EEG) recordings, ictal events were observed in five patients and quantitative comparisons of interictal spike and ictal seizure onset source localizations were made. In the eight patients who had presented with sensorimotor seizure, source localization of cortical sites concordant with seizure foci was determined using somatosensory functional mapping, and the results were quantitatively compared with interictal spike source localizations. Interictal spike sources demonstrated on MEG localized to the same region as the corresponding ictal event or somatosensory source localizations. The mean distance between the ictal foci and interictal spike sources was 1.1 +/- 0.3 cm. Results of functional somatosensory mapping in patients with sensorimotor seizures demonstrated that seizure sources consistently colocalized with interictal MEG spike sources, with a mean distance of 1.5 +/- 0.4 cm. No systematic directional bias was observed. Interictal sources tended to be tightly clustered, and the mean ellipsoid volume, defined by one standard deviation of the source spatial coordinates, was 1 cm3. CONCLUSIONS: Interictal spike localizations on MEG were concordant with ictal and, where relevant, functional somatosensory mapping localizations. These findings support the interpretation of interictal spikes on MEG as a useful and effective noninvasive method for localizing primary seizure foci.

Adolescent↗
PubMed2002

Neuromagnetic auditory cortex responses to duration and pitch changes in tones: cross-linguistic comparisons of human subjects in directions of acoustic changes.

Our recent magnetic mismatch field (MMF) study found that shortened-vowel duration changes and level-to-falling pitch changes in Japanese words elicited a prominent MMF in two hemispheres for both native and nonnative speakers (Inouchi, M., Kubota, M., Ferrari, P. and Roberts, T.P.L., Magnetic mismatch fields elicited by Japanese words: vowel duration and pitch by native and nonnative speakers, Poster presented at the 31st Annual Meeting of Society for Neuroscience, November 10-15, San Diego, CA, 2001). The current study investigated whether shortened duration changes and level-to-falling pitch changes in non-speech (tones) would elicit a more prominent MMF component than lengthened duration changes and falling-to-level pitch changes, respectively. Stimuli included three computer-synthesized tones with varying duration or frequency modulation: (1). short duration and level pitch; (2). long duration and level pitch; (3). long duration and falling pitch. Magnetoencephalography responses were recorded with a dual 37-channel gradiometer system. The results showed that the prominent MMF component was generated in long-to-short duration changes and level-to-falling pitch changes in each hemisphere for both Japanese and American subjects. The component peaked at around 100 ms after change onset for duration changes and 170 ms for pitch changes. The MMF component in tones, like in words, was particularly sensitive to duration shortening and pitch falling. In summary, changes in duration shortening and pitch falling are particularly salient cues for pre-attentive auditory change detection in each hemisphere.

Adult↗
PubMed2002

Increased somatosensory neuromagnetic fields ipsilateral to lesions in neurosurgical patients.

This study is aimed to determine whether the presence of a tumor in close proximity to the somatosensory cortex of the post-central gyrus affects the response evoked from such an area by painless tactile stimulation, recorded by MEG. The main finding of this study is that somatosensory evoked field strengths from cortex ipsilateral to and abutting an intracranial tumor are significantly elevated compared with either contralateral control fields, or with somatosensory evoked fields elicited from cortex ipsilateral to, but distant from tumors (typically involving language areas, such as inferior frontal lobe). Biophysical and biochemical explanations implicate hyperactivity of cortical neurons close to the tumor, suggesting a possible role of MEG as a measure of tumor infiltration.

Brain Neoplasms↗
PubMed2002

Preoperative magnetic source imaging for brain tumor surgery: a quantitative comparison with intraoperative sensory and motor mapping.

OBJECT: The aim of this study was to compare quantitatively the methods of preoperative magnetic source (MS) imaging and intraoperative electrophysiological cortical mapping (ECM) in the localization of sensorimotor cortex in patients with intraaxial brain tumors. METHODS: Preoperative magnetoencephalography (MEG) was performed while patients received painless tactile somatosensory stimulation of the lip, hand, and foot. The early somatosensory evoked field was modeled using a single equivalent current dipole approach to estimate the spatial source of the response. Three-dimensional magnetic resonance image volume data sets with fiducials were coregistered with the MEG recordings to form the MS image. These individualized functional brain maps were integrated into a neuronavigation system. Intraoperative mapping of somatosensory and/or motor cortex was performed and sites were compared. In two subgroups of patients we compared intraoperative somatosensory and motor stimulation sites with MS imaging-based somatosensory localizations. Mediolateral projection of the MS imaging source localizations to the cortical surface reduced systematic intermodality discrepancies. The distance between two corresponding points determined using MS imaging and ECM was 12.5 +/- 1.3 mm for somatosensory-somatosensory and 19 +/- 1.3 mm for somatosensory-motor comparisons. The observed 6.5 mm increase in site separation was systematically demonstrated in the anteroposterior direction, as expected from actual anatomy. In fact, intraoperative sites at which stimulation evoked the same patient response exhibited a spatial variation of 10.7 +/- 0.7 mm. CONCLUSIONS: Preoperative MS imaging and intraoperative ECM show a favorable degree of quantitative correlation. Thus, MS imaging can be considered a valuable and accurate planning adjunct in the treatment of patients with intraaxial brain tumors.

Adolescent↗