Neural underpinnings of processing combinatorial unstated meaning and the influence of individual cognitive style.

We investigated the neurocognitive mechanisms underlying the processing of combinatorial unstated meaning. Sentences like "Charles jumped for 5 minutes." engender an iterative meaning that is not explicitly stated but enriched by comprehenders beyond simple composition. Comprehending unstated meaning involves meaning contextualization-integrative meaning search in sentential-discourse context. Meanwhile, people differ in how they process information with varying context sensitivity. We hypothesized that unstated meaning processing would vary with individual socio-cognitive propensity indexed by the Autism-Spectrum Quotient (AQ), accompanied by differential cortical engagements. Using functional magnetic resonance imaging, we examined the processing of sentences with unstated iterative meaning in typically-developed individuals and found an engagement of the fronto-parietal network, including the left pars triangularis (L.PT), right intraparietal (R.IPS), and parieto-occipital sulcus (R.POS). We suggest that the L.PT subserves a contextual meaning search, while the R.IPS/POS supports enriching unstated iteration in consideration of event durations and interval lengths. Moreover, the activation level of these regions negatively correlated with AQ. Higher AQ ties to lower L.PT activation, likely reflecting weaker context sensitivity, along with lower IPS activation, likely reflecting weaker computation of events' numerical-temporal specifications. These suggest that the L.PT and R.IPS/POS support the processing of combinatorial unstated meaning, with the activation level modulated by individual cognitive styles.

Sentential inference bridging between lexical/grammatical knowledge and text comprehension among native Chinese speakers learning Japanese.

The current study explored the role of sentential inference in connecting lexical/grammatical knowledge and overall text comprehension in foreign language learning. Using structural equation modeling (SEM), causal relationships were examined between four latent variables: lexical knowledge, grammatical knowledge, sentential inference, and text comprehension. The study analyzed 281 Chinese university students learning Japanese as a second language and compared two causal models: (1) the partially-mediated model, which suggests that lexical knowledge, grammatical knowledge, and sentential inference concurrently influence text comprehension, and (2) the wholly-mediated model, which posits that both lexical and grammatical knowledge impact sentential inference, which then further affects text comprehension. The SEM comparison analysis supported the wholly-mediated model, showing sequential causal relationships from lexical knowledge to sentential inference and then to text comprehension, without significant contribution from grammatical knowledge. The results indicate that sentential inference serves as a crucial bridge between lexical knowledge and text comprehension.

Everyday Language Exposure Shapes Prediction of Specific Words in Listening Comprehension: A Visual World Eye-Tracking Study.

We investigated the effects of everyday language exposure on the prediction of orthographic and phonological forms of a highly predictable word during listening comprehension. Native Japanese speakers in Tokyo (Experiment 1) and Berlin (Experiment 2) listened to sentences that contained a predictable word and viewed four objects. The critical object represented the target word (e.g., /sakana/; fish), an orthographic competitor (e.g., /tuno/; horn), a phonological competitor (e.g., /sakura/; cherry blossom), or an unrelated word (e.g., /hon/; book). The three other objects were distractors. The Tokyo group fixated the target and the orthographic competitor over the unrelated objects before the target word was mentioned, suggesting that they pre-activated the orthographic form of the target word. The Berlin group showed a weaker bias toward the target than the Tokyo group, and they showed a tendency to fixate the orthographic competitor only when the orthographic similarity was very high. Thus, prediction effects were weaker in the Berlin group than in the Tokyo group. We found no evidence for the prediction of phonological information. The obtained group differences support probabilistic models of prediction, which regard the built-up language experience as a basis of prediction.

Abstractness of human speech sound representations.

We argue, based on a study of brain responses to speech sound differences in Japanese, that memory encoding of functional speech sounds-phonemes-are highly abstract. As an example, we provide evidence for a theory where the consonants/p t k b d g/ are not only made up of symbolic features but are underspecified with respect to voicing or laryngeal features, and that languages differ with respect to which feature value is underspecified. In a previous study we showed that voiced stops are underspecified in English [Hestvik, A., & Durvasula, K. (2016). Neurobiological evidence for voicing underspecification in English. Brain and Language], as shown by asymmetries in Mismatch Negativity responses to /t/ and /d/. In the current study, we test the prediction that the opposite asymmetry should be observed in Japanese, if voiceless stops are underspecified in that language. Our results confirm this prediction. This matches a linguistic architecture where phonemes are highly abstract and do not encode actual physical characteristics of the corresponding speech sounds, but rather different subsets of abstract distinctive features.

The Interplay of Relational and Non-relational Processes in Sentence Production: The Case of Relative Clause Planning in Japanese and Spanish.

Speech planning involves different steps in order to transform a conceptual message into speech. These include establishing structural relations among constituents (i.e., relational information), and selecting the appropriate lexical items to convey the intended message (non-relational elements). However, the precise way relational and non-relational information are computed when undertaking linguistic encoding is not clear. This paper explores how the pre-linguistic message undergoes linguistic encoding, and what kind of information (relational or non-relational) is prioritized in doing so. We analyze the production planning of Relative Clauses in Spanish (a head-initial language) and Japanese (a head-final language) by monolingual speakers, by means of the eye-tracking method while participants described colored pictures. Although in both Spanish and Japanese the structure under study is the same (with the same syntactic configuration), word order is entirely opposite between both languages. In Japanese, the head noun is not uttered until the end of the clause, thus making it possible to explore sentence planning in a structure where the syntactically most dominant element (the head noun, HN) is not the first element. Variables tested were type of relative clause, with either the agent or the patient as head noun, and the animacy of the agent and the patient of the event, the latter allowing the manipulation of the conceptual saliency of the elements involved. Results showed Japanese speakers focus extensively on the HN before directing their gazes to the element they are going to utter first, suggesting a speech planning process that prioritizes relational information, that is, structural scaffolding. Spanish monolinguals, in turn, showed a pattern in which both structural and linear information appear to be more closely related from the beginning. In both languages, the animacy of isolated elements had little effect on gaze patterns. Results point to a planning process that prioritizes structural relations over access to lexical elements in order in the planning of complex structures, with room for flexibility when the grammar of the language allows so.

Acid-inducible proton influx currents in the plasma membrane of murine osteoclast-like cells.

Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H(+)-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast-like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na(+), Cl(-), and HCO3 (-), suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato-2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A1 and N,N'-dicyclohexylcarbodiimide. Extracellular Ca(2+) (10 mM) did not affect the currents, but 1 mM ZnCl2 decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H(+) influx currents, which caused overshoot of the voltage-gated H(+) channels after removal of acids. The H(+) influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H(+) influx (H(+) leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids.

Increases in intracellular pH facilitate endocytosis and decrease availability of voltage-gated proton channels in osteoclasts and microglia.

Voltage-gated proton channels (H(+) channels) are highly proton-selective transmembrane pathways. Although the primary determinants for activation are the pH and voltage gradients across the membrane, the current amplitudes fluctuate often when these gradients are constant. The aim of this study was to investigate the role of the intracellular pH (pHi) in regulating the availability of H(+) channels in osteoclasts and microglia. In whole-cell clamp recordings, the pHi was elevated after exposure to NH4Cl and returned to the control level after washout. However, the H(+) channel conductance did not recover fully when the exposure was prolonged (>5 min). Similar results were observed in osteoclasts and microglia, but not in COS7 cells expressing a murine H(+) channel gene (mVSOP). As other electrophysiological properties, like the gating kinetics and voltage dependence for activation, were unchanged, the decreases in the H(+) channel conductance were probably due to the decreases in H(+) channels available at the plasma membrane. The decreases in the H(+) channel conductances were accompanied by reductions in the cell capacitance. Exposure to NH4Cl increased the uptake of the endocytosis marker FM1-43, substantiating the idea that pHi increases facilitated endocytosis. In osteoclasts, whose plasma membrane expresses V-ATPases and H(+) channels, pHi increases by these H(+)-transferring molecules in part facilitated endocytosis. The endocytosis and decreases in the H(+) channel conductance were reduced by dynasore, a dynamin blocker. These results suggest that pHi increases in osteoclasts and microglia decrease the numbers of H(+) channels available at the plasma membrane through facilitation of dynamin-dependent endocytosis.

Phospholipase C-dependent Ca2+-sensing pathways leading to endocytosis and inhibition of the plasma membrane vacuolar H+-ATPase in osteoclasts.

In osteoclasts, elevation of extracellular Ca2+ is an endogenous signal that inhibits bone resorption. We recently found that an elevation of extracellular Ca2+ decreased proton extrusion through the plasma membrane vacuolar H+-ATPase (V-ATPase) rapidly. In this study we investigated mechanisms underlying this early Ca2+-sensing response, particularly in reference to the activity of the plasma membrane V-ATPase and to membrane retrieval. Whole cell clamp recordings allowed us to measure the V-ATPase currents and the cell capacitance (C(m)) simultaneously. C(m) is a measure of cell surface. Extracellular Ca2+ (2.5-40 mM) decreased C(m) and the V-ATPase current simultaneously. The decreased C(m), together with the enhanced uptake of a lipophilic dye (FM1-43), indicated that Ca2+ facilitated endocytosis. The endocytosis was blocked by dynamin inhibitors (dynasore and dynamin-inhibitory peptide), by small interfering RNA (siRNA) targeting for dynanmin-2 and also by bafilomycin A(1), a blocker of V-ATPases. The extracellular Ca2+-induced endocytosis and inhibition of the V-ATPase current were diminished by a phospholipase C inhibitor (U73122) and siRNA targeting for phospholipase C gamma2 subunit. Holding the cytosolic Ca2+ at either high (0.5-5 microM) or low levels or inhibiting calmodulin by an inhibitor (W7) or an antibody (anti-CaM) decreased the stimulated endocytosis and the inhibition of the V-ATPase current. These data suggest that extracellular Ca2+ facilitated dynamin- and V-ATPase-dependent endocytosis in association with an inhibition of the plasma membrane V-ATPase. Phospholipase C, cytosolic Ca2+, and calmodulin were involved in the signaling pathways. Membrane retrieval and the plasma membrane V-ATPase activity may cooperate during the early phase of Ca2+-sensing response in osteoclasts.

Temperature dependence of proton permeation through a voltage-gated proton channel.

Voltage-gated proton channels are found in many different types of cells, where they facilitate proton movement through the membrane. The mechanism of proton permeation through the channel is an issue of long-term interest, but it remains an open question. To address this issue, we examined the temperature dependence of proton permeation. Under whole cell recordings, rapid temperature changes within a few milliseconds were imposed. This method allowed for the measurement of current amplitudes immediately before and after a temperature jump, from which the ratios of these currents (Iratio) were determined. The use of Iratio for evaluating the temperature dependence minimized the contributions of factors other than permeation. Temperature jumps of various degrees (DeltaT, -15 to 15 degrees C) were applied over a wide temperature range (4-49 degrees C), and the Q10s for the proton currents were evaluated from the Iratios. Q10 exhibited a high temperature dependence, varying from 2.2 at 10 degrees C to 1.3 at 40 degrees C. This implies that processes with different temperature dependencies underlie the observed Q10. A novel resistivity pulse method revealed that the access resistance with its low temperature dependence predominated in high temperature ranges. The measured temperature dependence of Q10 was decomposed into Q10 of the channel and of the access resistances. Finally, the Q10 for proton permeation through the voltage-gated proton channel itself was calculated and found to vary from 2.8 at 5 degrees C to 2.2 at 45 degrees C, as expected for an activation enthalpy of 64 kJ/mol. The thermodynamic features for proton permeation through proton-selective channels were discussed for the underlying mechanism.

Syntax in a native language still continues to develop in adults: honorification judgment in Japanese.

Native languages (L1s) are tacitly assumed to be complete and stable in adults. Here we report an unexpected individual variation in judgment of L1 regarding Japanese sentences including honorification, and further clarify its neural basis with functional magnetic resonance imaging (fMRI). By contrasting an honorification judgment task with a spelling judgment task, the lower performance group showed more extensive activation in the left inferior frontal gyrus than did the higher performance group. Moreover, activation in the left dorsal and ventral triangular parts negatively correlated with the performance of the honorification judgment task. This modulation pattern demonstrates that cortical activations recruited for sentence processing depend on individual performances even in L1.

Early and late activation of the voltage-gated proton channel during lactic acidosis through pH-dependent and -independent mechanisms.

Voltage-gated proton (H+) channels play a pivotal role in compensating charge and pH imbalances during respiratory bursts in phagocytes. Lactic acidosis is a clinically important metabolic condition accompanying various tissue disorders in which the extracellular pH and the intracellular pH often change in parallel. In this study, we investigated the responses of the H+ channel in microglia to lactate-induced pH disturbances using the perforated-patch recordings. Na-lactate (pH 6.8) acidified the cells and activated the H+ channel within 5 min. This early activation was correlated with increases in the pH gradient across the plasma membrane (DeltapH) and was dose-dependent over a concentration range of 10-150 mM. At 10 mM, the change in DeltapH was only slight, but the H+ currents continued to increase over an hour after the cell acidosis was stabilized. Prolonged exposure to lactate (10-20 mM, >1 h) increased the amplitude by two to threefold. The late activation was not explained by increased DeltapH but by changes in the property of the channel per se. Pretreatment with staurosporine and chelerythrine, inhibitors for protein kinase C, prevented the late activation. These results suggest that the H+ channel could be activated greatly during long-lasting lactic acidosis through both DeltapH-dependent and -independent mechanisms.

pH dependence and inhibition by extracellular calcium of proton currents via plasmalemmal vacuolar-type H+-ATPase in murine osteoclasts.

The vacuolar-type H(+)-ATPase (V-ATPase) in the plasma membrane of a variety of cells serves as an acid-secreting pathway, and its activity is closely related to cellular functions. Massive proton secretion often leads to electrolyte disturbances in the vicinity of the cell and may in turn affect the activity of the V-ATPase. We characterized, for the first time, the proton currents mediated by plasmalemmal V-ATPase in murine osteoclast-like cells and investigated its activity over a wide range of pH gradients across the membrane (DeltapH = extracellular pH - intracellular pH). The V-ATPase currents were identified as outward H(+) currents and were dependent on ATP and sensitive to the inhibitors bafilomycin A(1) and N,N'-dicyclohexylcarbodiimide. Although H(+) was transported uphill, the electrochemical gradient for H(+) affected the current. The currents were increased by elevating DeltapH and depolarization, and were reduced by lowering DeltapH and hyperpolarization. Elevation of extracellular Ca(2+) (5-40 mm) diminished the currents in a dose-dependent manner and made the voltage dependence more marked. Extracellular Mg(2+) mimicked the inhibition. With 40 mm Ca(2+), the currents decreased to < 40% at 0 mV and to < 10% at about -80 mV. Increases in the intracellular Ca(2+) (0.5-5 microm) did not affect the current. The data suggest that acid secretion through the plasmalemmal V-ATPase is regulated by a combination of the pH gradient, the membrane potential and the extracellular divalent cations. In osteoclasts, the activity-dependent accumulation of acids and Ca(2+) in the closed extracellular compartment might serve as negative feedback signals for regulating the V-ATPase.

Priority information used for the processing of Japanese sentences: thematic roles, case particles or grammatical functions?

The present study investigated scrambling effects on the processing of Japanese sentences and priority information used among thematic roles, case particles and grammatical functions. Reaction times for correct sentence decisions were significantly prolonged for scrambled active sentences with transitive verbs in the first experiment and with ditransitive verbs in the second experiment. Errors were made with scrambled sentences more than canonical sentences in both experiments, which suggested that scrambling effects were apparent in active sentences. Passive sentences in the third experiment indicated that canonical order defined based on case particles, not thematic roles, was more quickly and accurately identified than scrambled order. Potential sentences in the fourth experiment and causative sentences in the fifth experiment indicated that the processing of scrambled sentences based on grammatical functions, but not on case particles, required longer reaction times and resulted in higher error rates than canonical sentences. Consequently, scrambling effects in the present study indicated that neither thematic roles nor case particles can provide fully-satisfactory information for canonical phrase order, and that only grammatical functions offer satisfactory information in all types of sentences.

Regulatory mechanisms and physiological relevance of a voltage-gated H+ channel in murine osteoclasts: phorbol myristate acetate induces cell acidosis and the channel activation.

UNLABELLED: The voltage-gated H+ channel is a powerful H+ extruding mechanism of osteoclasts, but its functional roles and regulatory mechanisms remain unclear. Electrophysiological recordings revealed that the H+ channel operated on activation of protein kinase C together with cell acidosis. INTRODUCTION: H+ is a key signaling ion in bone resorption. In addition to H+ pumps and exchangers, osteoclasts are equipped with H+ conductive pathways to compensate rapidly for pH imbalance. The H+ channel is distinct in its strong H+ extrusion ability and voltage-dependent gatings. METHODS: To investigate how and when the H+ channel is available in functional osteoclasts, the effects of phorbol 12-myristate 13-acetate (PMA), an activator for protein kinase C, on the H+ channel were examined in murine osteoclasts generated in the presence of soluble RANKL (sRANKL) and macrophage-colony stimulating factor (M-CSF). RESULTS AND CONCLUSIONS: Whole cell recordings clearly showed that the H+ current was enhanced by increasing the pH gradient across the plasma membrane (delta(pH)), indicating that the H+ channel changed its activity by sensing delta(pH). The reversal potential (V(rev)) was a valuable tool for the real-time monitoring of delta(pH) in clamped cells. In the permeabilized patch, PMA (10 nM-1.6 microM) increased the current density and the activation rate, slowed decay of tail currents, and shifted the threshold toward more negative voltages. In addition, PMA caused a negative shift of V(rev), suggesting that intracellular acidification occurred. The PMA-induced cell acidosis was confirmed using a fluorescent pH indicator (BCECF), which recovered quickly in a K(+)-rich alkaline solution, probably through the activated H+ channel. Both cell acidosis and activation of the H+ channel by PMA were inhibited by staurosporine. In approximately 80% of cells, the PMA-induced augmentation in the current activity remained after compensating for the delta(pH) changes, implying that both delta(pH)-dependent and -independent mechanisms mediated the channel activation. Activation of the H+ channel shifted the membrane potential toward V(rev). These data suggest that the H+ channel may contribute to regulation of the pH environments and the membrane potential in osteoclasts activated by protein kinase C.

The effects of phrase-length order and scrambling in the processing of visually presented Japanese sentences.

The present study investigated the effects of phrase length and scrambling in the processing of Japanese sentences. Reading times of short phrases, long phrases, verbs, and whole sentences, measured by the method of self-paced reading, did not differ in terms of phrase-length order and scrambling. In addition, four types of sentences constructed on the basis of phrase-length order and scrambling did not affect duration times of correctness decision-making for sentences. However, error rates differed between canonical and scrambled sentences regardless of phrase-length order. This result implies that scrambled sentences were harder to judge as correct sentences than canonical sentences. Thus, scrambling affects the appropriate integration of information, whereas phrase-length order is simply an indication of preference and not of cognitive processing. To explain the present result, the authors propose the "configurational structure without movement," which predicts no difference in speed between the processing of canonical and scrambled sentences, apart from error rates.

A voltage-gated H+ channel is a powerful mechanism for pH homeostasis in murine osteoclasts.

Osteoclasts secrete a large amount of proton (H+) ions and proteolytic enzymes into bone resorption pit to degrade bone matrix. In addition to H+ pumps and exchangers, voltage-gated H+ channels, which are H+ conductive pathways, are expressed in osteoclasts. H+ channels are distinct in their strong H+ extrusion ability, but the functional role is not clear. This is the first study of H+ channels in murine osteoclasts generated from mononuclear precursors in the presence of a soluble form of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (M-CSF). The H+ channel was characterized by voltage- and pH-dependent activation, slow activation kinetics, and outward rectification. The reversal potential (Vrev) was shifted to more positive potentials by decreasing the pH gradient across the plasma membrane (deltapH). Employing Vrev as a real time monitor of pH in clamped cells, it is revealed that the H+ channel activation could decrease deltapH by approximately 0.43 unit/s. Decline in the current during prolonged depolarizations was accompanied by a positive shift in Vrev. This implies that the H+ channel activity is auto-regulated by sensing deltapH, to compensate for pH imbalance. The H+ current-density in cells with 36 nuclei was significantly smaller than that in cells with < or =5 nuclei, although the activation rate was unaltered. Thus, the H+ channel activity may alter during osteoclastogenesis. These data suggest the H+ channel is a powerful mechanism for pH homeostasis of osteoclasts that are exposed to drastic change in pH environments during the bone resorption cycle.

Cell swelling as an intermediate signal leading to activation of a Cl- channel in extracellular calcium-sensing of murine osteoclasts.

Osteoclasts possess extracellular Ca2+-sensing machinery to regulate bone-resorbing activity. In murine osteoclasts, an elevation of the extracellular Ca2+ concentration activated a volume-sensitive outwardly rectifying Cl- (OR(Cl)) channel. Exposure to 40 mM Ca2+ activated the OR(Cl) current in association with an increase in the planar cell area. An actin-destabilizer (cytochalasin D), removal of a major extracellular osmolyte (Na+), and a blocker for the Na+/Ca2+ exchanger (2'4'-dichlorobenzamil hydrochloride) inhibited both swelling and activation of the OR(Cl) channel by extracellular Ca2+. There was a positive correlation between the current density and increment in the cell area. The extracellular Ca2+-induced swelling was confirmed in intact (unclamped) cells by three-dimensional analysis using confocal scanning microscopy with a fluorescent dye (BCECF) in the extracellular medium. These results suggest that swelling is an intermediate signal for extracellular Ca2+ sensing of osteoclasts, which leads to activation of the OR(Cl) channel. Cell volume may be a second-message in the regulation of osteoclast function.