Lateralization and Time-Course of Cortical Phonological Representations during Syllable Production.

Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain's speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography (ECoG) recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode's response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represented evenly throughout trials, and syllables during production. Locations of strongly speech-encoding electrodes (the top 30% of electrodes) likewise depended on phonological element duration, with consonant-encoding electrodes left-lateralized, vowel-encoding hemispherically balanced, and syllable-encoding right-lateralized. The lateralization of speech-encoding electrodes depended on onset time, with electrodes active before or after speech production favoring left hemisphere and those active during speech favoring the right. Single-electrode speech classification revealed cortical areas with preferential encoding of particular phonemic elements, including consonant encoding in the left precentral and postcentral gyri and syllable encoding in the right middle frontal gyrus. Our findings support neurolinguistic theories of left hemisphere specialization for processing short-timescale linguistic units and right hemisphere processing of longer-duration units.

Whey protein consumption after resistance exercise reduces energy intake at a post-exercise meal.

PURPOSE: Protein consumption after resistance exercise potentiates muscle protein synthesis, but its effects on subsequent appetite in this context are unknown. This study examined appetite and energy intake following consumption of protein- and carbohydrate-containing drinks after resistance exercise. METHODS: After familiarisation, 15 resistance training males (age 21 ± 1 years, body mass 78.0 ± 11.9 kg, stature 1.78 ± 0.07 m) completed two randomised, double-blind trials, consisting of lower-body resistance exercise, followed by consumption of a whey protein (PRO 23.9 ± 3.6 g protein) or dextrose (CHO 26.5 ± 3.8 g carbohydrate) drink in the 5 min post-exercise. An ad libitum meal was served 60 min later, with subjective appetite measured throughout. Drinks were flavoured and matched for energy content and volume. The PRO drink provided 0.3 g/kg body mass protein. RESULTS: Ad libitum energy intake (PRO 3742 ± 994 kJ; CHO 4172 ± 1132 kJ; P = 0.007) and mean eating rate (PRO 339 ± 102 kJ/min; CHO 405 ± 154 kJ/min; P = 0.009) were lower during PRO. The change in eating rate was associated with the change in energy intake (R = 0.661, P = 0.007). No interaction effects were observed for subjective measures of appetite. The PRO drink was perceived as creamier and thicker, and less pleasant, sweet and refreshing (P < 0.05). CONCLUSION: These results suggest whey protein consumption after resistance exercise reduces subsequent energy intake, and this might be partially mediated by a reduced eating rate. Whilst this reduced energy intake is unlikely to impair hypertrophy, it may be of value in supporting an energy deficit for weight loss.

Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles.

Surface chemistry plays a deciding role in nanoparticle biodistribution, yet very little is known about how surface chemistry influences the suborgan distributions of nanomaterials. Here, using quantitative imaging based on laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), we demonstrate that surface charge dictates the suborgan distributions of nanoparticles in the kidney, liver, and spleen of mice intravenously injected with functionalized gold nanoparticles. Images of the kidney show that positively charged nanoparticles accumulate extensively in the glomeruli, the initial stage in filtering for the nephron, suggesting that these nanoparticles may be filtered by the kidney at a different rate than the neutral or negatively charged nanoparticles. We find that positively and negatively charged nanoparticles accumulate extensively in the red pulp of the spleen. In contrast, uncharged nanoparticles accumulate in the white pulp and marginal zone of the spleen to a greater extent than the positively or negatively charged nanoparticles. Moreover, these uncharged nanoparticles are also more likely to be found associated with Kupffer cells in the liver. Positively charged nanoparticles accumulate extensively in liver hepatocytes, whereas negatively charged nanoparticles show a broader distribution in the liver. Together these observations suggest that neutral nanoparticles having 2 nm cores may interact with the immune system to a greater extent than charged nanoparticles, highlighting the value of determining the suborgan distributions of nanomaterials for delivery and imaging applications.

Ubiquitination as a Mechanism To Transport Soluble Mycobacterial and Eukaryotic Proteins to Exosomes.

Exosomes are extracellular vesicles of endocytic origin that function in intercellular communication. Our previous studies indicate that exosomes released from Mycobacterium tuberculosis-infected macrophages contain soluble mycobacterial proteins. However, it was unclear how these secreted proteins were targeted to exosomes. In this study, we determined that exosome production by the murine macrophage cell line RAW264.7 requires the endosomal sorting complexes required for transport and that trafficking of mycobacterial proteins from phagocytosed bacilli to exosomes was dependent on protein ubiquitination. Moreover, soluble mycobacterial proteins, when added exogenously to RAW264.7 or human HEK293 cells, were endocytosed, ubiquitinated, and released via exosomes. This suggested that endocytosed proteins could be recycled from cells through exosomes. This hypothesis was supported using the tumor-associated protein He4, which, when endocytosed by RAW264.7 or HEK293 cells, was transported to exosomes in a ubiquitin-dependent manner. Our data suggest that ubiquitination is a modification sufficient for trafficking soluble proteins within the phagocytic/endocytic network to exosomes.