MT neurons in the macaque exhibited two types of bimodal direction tuning as predicted by a model for visual motion detection

AbstractWe previously proposed a model for detecting local image velocity on the magnocellular visual pathway (Kawakami & Okamoto (1996) Vision Research, 36, 117–147). The model detects visual motion in two stages using the hierarchical network that includes component and pattern cells in area MT. To validate the model, we predicted two types of bimodal direction tuning for MT neurons. The first type is characteristic of component cells. The tuning is bimodal when stimulated with high-speed spots, but unimodal for low-speed spots or for bars. The interval between the two peaks widens as the spot’s speed increases. The second type is characteristic of pattern cells. The tuning is bimodal when stimulated with low-speed bars, but unimodal for high-speed bars or for spots. The interval widens as the bar’s speed decreases. To confirm this prediction, we studied the change of direction tuning curves for moving spots and bars in area MT of macaque monkeys. Out of 35 neurons measured at various speeds, six component cells and four pattern cells revealed the predicted bimodal tunings. This result provided neurophysiological support for the validity of the model. We believe ours is the first systematic study that records the two types of bimodality in MT neurons

Anti-Integrin Therapy for Multiple Sclerosis

Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin

The use of electrogastrography and external ultrasonography to evaluate gastric motility in Crohn’s disease

Although Crohn’s disease is associated with various digestive symptoms, there have been few reports on gastric motility. In this study, we conducted a study of gastric motility in Crohn’s disease using 20 healthy subjects (N group) and 15 patients with Crohn’s disease (C group) by electrogastrography (EGG) using a Nipro electrogastrograph. An EGG was recorded for 30 minutes in a fasting state and after ingestion of 300ml of a liquid meal. As an index of gastric emptying, the rate of change in the crosssectional area of the gastric antrum was measured 1 and 15 minutes after ingestion of the liquid meal by external ultrasonography. In an EGG frequency analysis, waveforms with a peak of 3 cycles/minute (cpm) were noted in the N group, and the peak amplitude increased significantly after the ingestion of food. In the C group, division of the normalgastria component was noted after the ingestion of food in 5 patients (33.3%). In a comparison of the peak amplitudes of fasting brady-gastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitude was significantly increased in normalgastria in the N group, and in brady-gastria and tachy-gastria in the C group. In a comparison of the rates of food ingestion-induced changes in the peak amplitudes for bradygastria, normal-gastria, and tachy-gastria between the N and C groups, the peak amplitudes were significantly increased in normal-gastria in the N group, but not in the C group. In the case of gastric emptying investigated by external ultrasonography, the rate of food ingestion-induced change in the cross-sectional antrum area was significantly lower in the C group (50.5±9.2%) than in the N group (65.0±8.5%). For gastrointestinal motility, a 3 cpm normal-gastria represents efficient gastric motility. In the C group, the peak amplitudes of brady-gastria and tachy-gastria were significantly increased, but were low in normal-gastria in the fasting EGG, postprandial division of the normal-gastria component was noted, and the rate of food ingestion-induced increase in the normal-gastria peak amplitude was significantly lower than that in the N group, suggesting that patients with Crohn’s disease have a functional abnormality in, not only the small and large intestine, but also the stomach

The Cell Surface Receptor SLAM Controls T Cell and Macrophage Functions

Signaling lymphocyte activation molecule (SLAM), a glycoprotein expressed on activated lymphocytes and antigen-presenting cells, has been shown to be a coregulator of antigen-driven T cell responses and is one of the two receptors for measles virus. Here we show that T cell receptor–induced interleukin (IL)-4 secretion by SLAM−/− CD4+ cells is down-regulated, whereas interferon γ production by CD4+ T cells is only slightly up-regulated. Although SLAM controls production of IL-12, tumor necrosis factor, and nitric oxide in response to lipopolysaccharide (LPS) by macrophages, SLAM does not regulate phagocytosis and responses to peptidoglycan or CpG. Thus, SLAM acts as a coreceptor that regulates signals transduced by the major LPS receptor Toll-like receptor 4 on the surface of mouse macrophages. A defective macrophage function resulted in an inability of SLAM−/− C57Bl/6 mice to remove the parasite Leishmania major. We conclude that the coreceptor SLAM plays a central role at the interface of acquired and innate immune responses

Cardiorespiratory fitness, body mass index, and cancer mortality: a cohort study of Japanese men

Background: The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods: We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results: Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion: These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI