Behavioral correlates of cortical semantic representations modeled by word vectors

The quantitative modeling of semantic representations in the brain plays a key role in understanding the neural basis of semantic processing. Previous studies have demonstrated that word vectors, which were originally developed for use in the field of natural language processing, provide a powerful tool for such quantitative modeling. However, whether semantic representations in the brain revealed by the word vector-based models actually capture our perception of semantic information remains unclear, as there has been no study explicitly examining the behavioral correlates of the modeled brain semantic representations. To address this issue, we compared the semantic structure of nouns and adjectives in the brain estimated from word vector-based brain models with that evaluated from human behavior. The brain models were constructed using voxelwise modeling to predict the functional magnetic resonance imaging (fMRI) response to natural movies from semantic contents in each movie scene through a word vector space. The semantic dissimilarity of brain word representations was then evaluated using the brain models. Meanwhile, data on human behavior reflecting the perception of semantic dissimilarity between words were collected in psychological experiments. We found a significant correlation between brain model- and behavior-derived semantic dissimilarities of words. This finding suggests that semantic representations in the brain modeled via word vectors appropriately capture our perception of word meanings.     

Integration of human mesenchymal stem cells into the Wolffian duct in chicken embryos

Developing animal embryos have been providing human mesenchymal stem cells (hMSCs) with an appropriate environment for their differentiation between species. We previously demonstrated that hMSCs transplanted into the metanephric mesenchyme region of rat embryos differentiate into kidney-specific cells. Here, we assessed whether hMSCs are competent to differentiate into precursors of the collecting duct system when they are transplanted into the ureteric bud progenitor region of chicken embryos that are easier to be manipulated and cultured than mammalian embryos. When chicken Pax2-expressing hMSCs were transplanted into the chicken ureteric bud progenitor region, they migrated caudally with the elongating Wolffian duct and then were integrated into the Wolffian duct epithelia. Also, chicken Pax2-expressing hMSCs started to express human LIM1 after their integration into the Wolffian duct epithelia. These results suggest that chicken Pax2-expressing hMSCs can be competent to differentiate into the Wolffian duct cells by the influence of chicken local signals.     

Diallyl sulfides in garlic activate both TRPA1 and TRPV1

We searched for novel agonists of TRP receptors especially for TRPA1 and TRPV1 in foods. We focused attention on garlic compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS). In TRPA1 or TRPV1 heterogeneously expressed CHO cells, all of those compounds increased [Ca²⁺]_i in concentration-dependent manner. The EC₅₀ values of DADS and DATS were similar to that of allyl isothiocyanate (AITC) and that of DAS was 170-fold larger than that of AITC. Maximum responses of these sulfides were equal to that of AITC. The EC₅₀ values of these compounds for TRPV1 were around 100 μM against that of capsaicin (CAP), 25.6 nM and maximum responses of garlic compounds were half to that of CAP. The Ca²⁺ responses were significantly suppressed by co-application of antagonist. We conclude that DAS, DADS, and DATS are agonist of both TRPA1 and TRPV1 but with high affinity for TRPA1.     

Expression of Green Fluorescent Protein Impairs the Force-Generating Ability of Isolated Rat Ventricular Cardiomyocytes

Green fluorescent protein (GFP) is widely used as a biologically inert expression marker for studying the effects of transgene expression in heart tissue, but its influence on the contractile function of cardiomyocytes has not yet been fully evaluated. We measured the contractile function of isolated rat ventricular myocytes before and after infection with a recombinant adenovirus expressing GFP (Adv-GFP). Myocytes infected with a non-transgene-containing adenovirus (Adv-Null) or uninfected myocytes (UI) served as controls. Using a carbon-fiber-based force-length measurement system for single cardiomyocytes, we evaluated the contractile function over a wide range of loading conditions including the shortening fraction (%FS) and maximal shortening velocity (Vmax) under the unloaded condition, and isometric force. At 24 hours after infection, nearly 80% of the Adv-GFP-infected myocytes expressed GFP. We found that the %FS and Vmax did not differ among the three groups, however, the isometric force showed a mild, but significant, decrease only in Adv-GFP myocytes (Adv-GFP: 29.1 ± 4.0 mN/mm²; Adv-Null: 42.8 ± 6.2 mN/mm²; UI: 47.1 ± 4.8 mN/mm²; p = 0.03). An evaluation of the contractile function of isolated cardiomyocytes under high load conditions revealed impaired isometric contractility by GFP expression. Adv-GFP expression may not be an ideal control for specific gene expression experiments in myocardial tissue.     

Substitution of the N-glycan function in glycosyltransferases by specific amino acids: ST3Gal-V as a model enzyme

The sialyltranferase ST3Gal-V transfers a sialic acid to lactosylceramide. We investigated the role of each of the N-glycans modifying mouse ST3Gal-V (mST3Gal-V) by measuring the in vitro enzyme activity of Chinese hamster ovary (CHO) cells transfected with ST3Gal-V cDNA or its mutants. By examining mutants of mST3Gal-V, in which each asparagine was replaced with glutamine (N180Q, N224Q, N334Q), we determined that all three sites are N-glycosylated and that each N-glycan is required for enzyme activity. Despite their importance, N-glycosylation sites in ST3Gal-V are not conserved among species. Therefore, we considered whether the function in the activity that is performed in mST3Gal-V by the N-glycan could be substituted for by specific amino acid residues selected from the ST3Gal-V of other species or from related sialyltransferases (ST3Gal-I, -II, -III, and -IV), placed at or near the glycosylation sites. To this end, we constructed a series of interspecies mutants for mST3Gal-V, specifically, mST3Gal-V-H177D-N180S (medaka or tetraodon type), mST3Gal-V-N224K (human type), and mST3Gal-V-T336Q (zebrafish type). The ST3Gal-V activity of these mutants was quite similar to that of the wild-type enzyme. Thus, we have demonstrated here that the N-glycans on mST3Gal-V are required for activity but can be substituted for specific amino acid residues placed at or near the glycosylation sites. We named this method SUNGA (substitution of N-glycan functions in glycosyltransferases by specific amino acids). Furthermore, we verified that the ST3Gal-V mutant created using the SUNGA method maintains its high activity when expressed in Escherichia coli thereby establishing the usefulness of the SUNGA method in exploring the function of N-glycans in vivo.     

Molecular dynamics of the blood–testis barrier components during murine spermatogenesis

The blood–testis barrier (BTB) separates the seminiferous epithelium into the adluminal and basal compartments. During murine spermatogenesis, preleptotene/leptotene spermatocytes migrate from the basal to the adluminal compartment through the BTB during stages VIII–IX. In the present study, we focused on the tight junction (TJ) molecules and analyzed their spatiotemporal expression during the murine seminiferous epithelial cycle. Structural analysis revealed that the principal components of the BTB, for example, claudin‐3, claudin‐11, occludin, and zonula occludens‐1 (ZO‐1), were localized at the basal and luminal sides of the preleptotene/leptotene spermatocytes during the migration stages (VIII–IX). Although we detected claudin‐11, occludin, and ZO‐1 throughout spermatogenesis, claudin‐3 was only detected during stages VI–IX. Quantitative PCR using dissected seminiferous tubules from three stages (Early: II–VI, Middle: VII–VIII, Late: IX–I) clarified that the mRNA levels of TJ molecules were not correlated with the histoplanimetrical protein levels during spermatogenesis. Additionally, tubulobulbar complexes, considered to be involved in the internalization of TJ, were observed at the BTB site. Furthermore, a significant reduction in the mRNA levels of genes for the degradation of occludin (Itch) and endocytic recycling (Rab13) were observed during the Late and Middle stages, respectively. Therefore, we hypothesized that the lag between mRNA and protein expression of TJ molecules may be due to posttranslational modulation, for example, tubulobulbar complexes and endocytic recycling processes. In conclusion, these findings indicate that the integrity of the BTB is maintained throughout spermatogenesis, and the stage‐specific localization of claudin‐3 protein plays an important role in regulating BTB permeability. Mol. Reprod. Dev. 77: 630–639, 2010. © 2010 Wiley‐Liss, Inc.     

Estimation of handgrip force using frequency-band technique during fatiguing muscle contraction

In this paper, we propose a force estimation model to compute the handgrip force from SEMG signal during fatiguing muscle contraction tasks. The appropriate frequency range was analyzed using various combinations of a wavelet scale, and the highest accuracy was achieved at a range from 242 to 365 Hz. After that, eight healthy individuals performed a series of static (70%, 50%, 30%, and 20% MVC) and dynamic (0–50% MVC) muscle contraction tasks to evaluate the performance of this technique in comparison with that of former method using the Root Mean Square of the SEMG signal. Both methods had comparable results at the beginning of the experiments, before the onset of muscle fatigue. However, differences were clearly observed as the degree of muscle fatigue began to increase toward the endurance time. Under this condition, the estimated handgrip force using the proposed method improved from 17% to 134% for static contraction tasks and 40% for dynamic contraction tasks. This study overcomes the limitation of the former method during fatiguing muscle contraction tasks and, therefore, unlocks the potential of utilizing the SEMG signal as an indirect force estimation method for various applications.     

Selective accumulation of a novel antimalarial rhodacyanine derivative, SSJ-127, in an organelle of Plasmodium berghei

SSJ-127, a novel antimalarial rhodacyanine derivative, has shown potent antimalarial activity against chloroquine-resistant Plasmodium strains in vitro and subcutaneous administration of SSJ-127 results in a complete cure of a mouse malaria model. SSJ-127 was detected by fluorescence microscopy in the mouse malaria parasites Plasmodium berghei after exposure of infected red blood cells to the compound in vitro and in vivo. Selective accumulation of SSJ-127 in an organelle is observed in all blood stages of live malaria parasites. The organelle is clearly different from the mitochondrion and the nucleus in terms of morphology. The shape of the organelle changed during the asexual blood stages of the parasite. There was always a close association between the organelle and the mitochondrion. These results raised the possibility that SSJ-127 accumulates in an apicoplast of the malaria parasite and affects protozoan parasite-specific pathways.