Visual long-term memory and change blindness: Different effects of pre- and post-change information on one-shot change detection using meaningless geometric objects.

To clarify the relationship between visual long-term memory (VLTM) and online visual processing, we investigated whether and how VLTM involuntarily affects the performance of a one-shot change detection task using images consisting of six meaningless geometric objects. In the study phase, participants observed pre-change (Experiment 1), post-change (Experiment 2), or both pre- and post-change (Experiment 3) images appearing in the subsequent change detection phase. In the change detection phase, one object always changed between pre- and post-change images and participants reported which object was changed. Results showed that VLTM of pre-change images enhanced the performance of change detection, while that of post-change images decreased accuracy. Prior exposure to both pre- and post-change images did not influence performance. These results indicate that pre-change information plays an important role in change detection, and that information in VLTM related to the current task does not always have a positive effect on performance.

A new lymphedema treatment using pyro-drive jet injection.

Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.

[Long-lasting implicit memory for unfamiliar faces revealed by an indirect recognition procedure].

We examined whether people can retain an implicit memory for unfamiliar faces over several weeks by using an indirect recognition procedure (Terasawa & Ohta, 1993). The procedure was composed of two sessions with a long-term interval. Two experiments using different intervals--19 days (Experiment 1) and 7 weeks (Experiment 2)--were conducted. In each session, participants were presented with line drawings of faces and were asked to rate their preferences. The number of presentations varied for each condition in the first session. Participants were also asked to perform an unexpected recognition test for the faces presented after the rating task in the second session. Results from both experiments showed that the rates of correct and false recognition of faces increased significantly with the number of presentations in the first session. The findings indicate that long-lasting implicit memory can be formed for unfamiliar faces by incidental learning.

Oral-specific microenvironments regulate cell behavior and anticancer drug sensitivity of tongue squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most major malignant tumor of the tongue. The tongue exists at the air-liquid interface and is covered with saliva. In addition, the tongue constituent cells and tongue cancer are present under fluid flow stimulation due to the abundant capillary network and contraction of muscle tissue. Therefore, replicating both cell-cell interactions (the cellular microenvironment) and the aforementioned physical microenvironment is very important for understanding the kinetics of tongue SCC. To elucidate the effects of the cellular and physical microenvironment on tongue SCC and to investigate the relationships between these factors, we developed a collagen cell disc, with double dish under a rotational culture method to generate cancer-stroma interactions and to create fluid flow stimulation. Mesenchymal cells, NIH-3T3 cells and tongue-derived fibroblasts influenced the proliferative potential. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by cellular interactions and fluid flow stimulation, depending on the SCC cell type. The cell-cell interactions and fluid flow stimulation independently, synergistically or contradictorily affected the behavior of tongue SCC. Fluid flow stimulation synergistically enhanced the antiproliferative effect of cis-diamminedichloroplatinum on tongue SCC cells, but mesenchymal cells abolished the synergistic antiproliferative effect related to fluid flow stimulation. In conclusion, a reconstructed model was established to investigate the cellular and physical microenvironments of tongue SCC in vitro. The newly established system is a promising model for the development of further regimes to treat general oral cancer.

Increased GLUT1 expression and localization to Golgi apparatus of acinar cells in the parotid gland of Goto-Kakizaki diabetic rats.

OBJECTIVE: Patients with diabetes are known to have high salivary glucose levels. But the mechanisms are still unclear. We hypothesized that the topological changes of glucose transporters affect the salivary glucose level. METHODS: We used adult Goto-Kakizaki (GK) rats, an animal model of advanced diabetes, and Wistar rats as a control, with or without glucose load. The sections of salivary glands from the animals were processed for standard histological, immunohistochemical, and immunofluorescent staining. RESULTS: Parotid acinar cells of GK rats appeared like mucous filled with low-eosin-stained granules and possessing a flat nucleus located basally, whereas those of Wistar rats appeared as a typical serous gland with eosin-rich cytoplasm and a spherical nucleus. Cytoplasmic granules of GK rat parotid acinar cells showed no reaction of polysaccharide staining. In acinar cell cytoplasm of GK rats, intense GLUT1 immunoreactivity was observed compared to Wistar rats. By double immunostaining for GLUT1 and Golgi apparatus-specific markers, it was determined that GLUT1 was localized to the Golgi apparatus. By glucose loading in starved GK rats, the distribution of GLUT1-immunoreactive signals was spread out clearly from the apical side of the nucleus to the basolateral side. CONCLUSIONS: In rat model of diabetes, highly localized GLUT1 at Golgi apparatus in acinar cells seems to increase taking up cytoplasmic glucose to form exocytotic vesicles. This phenomenon may transform parotid glands from serous to mucous-like and result in saccharide-rich saliva.

Microenvironmental elements singularity synergistically regulate the behavior and chemosensitivity of endometrioid carcinoma.

The importance of the microenvironment is widely recognized as it regulates not only malignant cell behavior but also drug sensitivity. The cancer cell microenvironment is composed of biological, physical and chemical elements, and simultaneous reproduction of these three elements are important conditions investigated in cancer research. In the present study, we focused on the epidemiological and anatomical specificities of endometrioid carcinoma, obesity (biological), fluid flow (physical) and anticancer agents (chemical) to target the specific microenvironmental elements of endometrioid carcinoma. To elucidate the individual effects of these elements on endometrioid carcinoma and to investigate the relationships between these factors, we developed an adipose tissue fragments (ATFs)-embedded cell disc under a rotational culture method to generate carcinoma-stroma interactions and to create fluid flow. ATFs and fluid flow individually or synergistically influenced proliferative cellular behavior and the morphological changes underlying endometrioid carcinoma. ATFs and fluid flow also governed the expression of extracellular signal-regulated kinase and p38 signaling synergistically or individually, depending on the endometrioid carcinoma cell type. Adipose tissue induced chemoresistance to cis-diamminedichloro-platinum (CDDP) in endometrioid cancer, but the resistance effect was abolished by fluid flow. Thus, a simple reconstructed model was established to investigate three elements of the microenvironment of endometrioid carcinoma in vitro. This culture model unequivocally demonstrated the individual and synergistic effects of the three elements on endometrioid carcinoma. This new culture model is a promising tool for elucidating the mechanisms underlying endometrioid carcinoma and for developing further treatment strategies.

Branched-chain amino acids prevent insulin-induced hepatic tumor cell proliferation by inducing apoptosis through mTORC1 and mTORC2-dependent mechanisms.

Branched-chain amino acids (BCAA) supplementation has been reported to suppress the incidence of liver cancer in obese patients with liver cirrhosis or in obese and diabetic model animals of carcinogenesis. Whether BCAA directly suppresses cell proliferation of hepatic tumor cells under hyperinsulinemic condition remain to be defined. The aim of this study was to investigate the effects of BCAA on insulin-induced proliferation of hepatic tumor cells and determine the underlying mechanisms. BCAA suppressed insulin-induced cell proliferation of H4IIE, HepG2 cells. In H4IIE cells, BCAA did not affect cell cycle progression but increased apoptosis by suppressing expressions of anti-apoptotic genes and inducing pro-apoptotic gene via inactivation of PI3K/Akt and NF-κB signaling pathways. Further studies demonstrated that BCAA inhibited PI3K/Akt pathway not only by promoting negative feedback loop from mammalian target of rapamycin complex 1 (mTORC1)/S6K1 to PI3K/Akt pathway, but also by suppressing mTORC2 kinase activity toward Akt. Our findings suggest that BCAA supplementation may be useful to suppress liver cancer progression by inhibiting insulin-induced PI3K/Akt and subsequent anti-apoptotic pathway, indicating the importance of BCAA supplementation to the obese patients with advanced liver disease.

Cell-Type-Specific Thalamocortical Inputs Constrain Direction Map Formation in Visual Cortex.

Finding the relationship between individual cognitive functions and cell-type-specific neuronal circuits is a central topic in neuroscience. In cats, the lateral geniculate nucleus (LGN) contains several cell types carrying spatially and temporally precise visual information. Whereas LGN cell types lack selectivity for motion direction, neurons in the primary visual cortex (area 17) exhibit sharp direction selectivity. Whether and how such de novo formation of direction selectivity depends on LGN cell types remains unknown. Here, we addressed this question using in vivo two-photon calcium imaging in cat area 17, which consists of two compartments receiving different combinations of inputs from the LGN cell types. The direction map in area 17 showed unique fragmented organization and was present only in small and distributed cortical domains. Moreover, direction-selective domains preferentially localized in specific compartments receiving Y and W inputs carrying low spatial frequency visual information, indicating that cell-type-specific thalamocortical projections constrain the formation of direction selectivity.

Long-term Branched Chain Amino Acid Supplementation Ameliorates Diethylnitrosamine-induced Liver Glutathione S-transferase-p Positivity in Zucker Fatty Rats.

BACKGROUND: Obesity increases the risk of fatty liver disease and liver cancer. There are several models of obesity-associated hepatocellular carcinoma, but tumor development in these models is slow. MATERIALS AND METHODS: We investigated Zucker fatty rats, a model of obesity and insulin resistance, to discover if diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver carcinogenesis. We also investigated the effect of branched chain amino acids (BCAA) against the development of liver cancer. RESULTS: Incidence and number of hepatocellular carcinomas and adenomas were significantly greater in DEN-treated Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats developed hepatocellular carcinoma within 16 weeks. Long-term BCAA supplementation significantly reduced expression of CyclinD1, PCNA, thymidine kinase, Bcl-2, and GST-p and increased expression of p21 in the liver. Furthermore, BCAA treatment significantly reduced the area of GST-p positive foci. CONCLUSION: Long-term BCAA treatment may induces cell cycle arrest and apoptotic induction, thus suppressing pre-neoplastic lesions.

Visual statistical learning based on the perceptual and semantic information of objects.

Five experiments examined what is learned based on the perceptual and semantic information of objects in visual statistical learning (VSL). In the familiarization phase, participants viewed a sequence of line drawings and detected repetitions of various objects. In a subsequent test phase, they watched 2 test sequences (statistically related triplets vs. unrelated foils) and decided whether the first or second sequence was more familiar based on the familiarization phase. In Experiment 1A, the test sequences comprised line drawings; in Experiment 1B, they comprised word stimuli representing each line drawing. The results showed that performance for statistically related triplets was greater than chance. In Experiments 2 and 3 containing the forward ABC and backward CBA triplets in the test, the results showed the importance of temporal order, especially in line drawings. In Experiment 4, in which the forward triplets were pitted against the backward triplets, we showed that temporal order is still important for the expression of VSL with word stimuli. Finally, in Experiment 5, we replicated the results of Experiments 2 and 3 even with the images of visual objects. These results suggest the parallel processes on the visual features and semantic information of objects in VSL.

Similarity of visual selectivity among clonally related neurons in visual cortex.

Neurons in rodent visual cortex are organized in a salt-and-pepper fashion for orientation selectivity, but it is still unknown how this functional architecture develops. A recent study reported that the progeny of single cortical progenitor cells are preferentially connected in the postnatal cortex. If these neurons acquire similar selectivity through their connections, a salt-and-pepper organization may be generated, because neurons derived from different progenitors are intermingled in rodents. Here we investigated whether clonally related cells have similar preferred orientation by using a transgenic mouse, which labels all the progeny of single cortical progenitor cells. We found that preferred orientations of clonally related cells are similar to each other, suggesting that cell lineage is involved in the development of response selectivity of neurons in the cortex. However, not all clonally related cells share response selectivity, suggesting that cell lineage is not the only determinant of response selectivity.