Serum withdrawal-induced apoptosis in ZrchI prion protein (PrP) gene-deficient neuronal cell line is suppressed by PrP, independent of Doppel

Previous studies have shown that cellular prion protein (PrP(C)) plays anti-apoptotic and antioxidative role against cell death induced by serum-deprivation (SDP) in an immortalized prion protein gene-deficient neuronal cell line derived from Rikn prion protein (PrP) gene-deficient (Prnp(-/-)) mice, which ectopically produce excess Doppel (Dpl) (PrP-like glycoprotein). To investigate whether PrP(C) inhibits apoptotic neuronal cell death without Dpl, an immortalized cell line was established from the brain of ZrchI Prnp(-/-) mice, which do not show ectopic expression of Dpl. The results using a ZrchI neuronal Prnp(-/-) cell line (NpL2) showed that PrP(C) potently inhibited SDP-induced apoptotic cell death. Furthermore, PrP(C) expression enhanced the superoxide dismutase (SOD) activity in NpL2 cells. These results indicate that Dpl production did not affect anti-apoptotic and anti-oxidative functions of PrP, suggesting that PrP(C) may be directly correlated with protection against oxidative stress.     

Interspecies Transmission of Feline Immunodeficiency Virus from the Domestic Cat to the Tsushima Cat (Felis bengalensis euptilura) in the Wild

Feline immunodeficiency virus (FIV) was isolated from a wild-caught Tsushima cat (Felis bengalensis euptilura), an endangered Japanese nondomestic subspecies of leopard cat (F. bengalensis). Phylogenetic analysis of the env gene sequences indicated that the FIV from the Tsushima cat belonged to a cluster of subtype D FIVs from domestic cats. FIVs from both the Tsushima cat and the domestic cat showed similar levels of replication and cytopathicity in lymphoid cell lines derived from these two species. The results indicated the occurrence of interspecies transmission of FIV from the domestic cat to the Tsushima cat in the wild.     

CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells

Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans-well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells.     

Environmental influences on fish assemblages in irrigation ponds

Ponds are common features of the landscape and are considered important for freshwater biodiversity conservation. Although fish have a significant impact on the lentic ecosystems, the environmental factors that regulate fish assemblages in human-created water bodies, such as irrigation ponds, remain unclear. We evaluated the relationship between environmental factors and the fish assemblage structure in 31 ponds located in northern Japan. Species richness (range: 1–9) was positively correlated with the size of the inflow channel. Multivariate analyses revealed that the size of the inflow channel was a better predictor for species richness than lake morphology (surface area and maximum depth), vegetation coverage, water quality (turbidity, pH, DO, and EC), distance to the main channel, and distance to an adjacent pond. Species richness was significantly different between ponds with and without an inflow channel. Furthermore, three of the four most commonly observed species are thought to be relatively tolerant to low oxygen. Given that ponds have a relatively high local extinction rate resulting from exposure to stressful conditions, such as low oxygen and/or small population sizes, our results suggest that immigration from surrounding water bodies plays an important role in maintaining species richness of pond-dwelling fish.     

Production and Characterization of Transgenic Mice Harboring Mutant Human UMOD Gene

Familial juvenile hyperuricemic nephropathy is caused by mutations in the UMOD gene encoding uromodulin. A transgenic mouse model was developed by introducing a human mutant UMOD (C148W) cDNA under control of the mouse umod promoter. Uromodulin accumulation was observed in the thick ascending limb cells in the kidney of transgenic mice. However, the urinary excretion of uromodulin in transgenic mice did not decrease and LC-MS/MS analysis indicated it was of mouse origin. Moreover, the creatinine clearance was not different between wildtype and transgenic animals. Consequently, the onset of the disease was not observed in transgenic mice until 24 weeks of age.     

Cultured Cortical Neurons Can Perform Blind Source Separation According to the Free-Energy Principle

Blind source separation is the computation underlying the cocktail party effect––a partygoer can distinguish a particular talker’s voice from the ambient noise. Early studies indicated that the brain might use blind source separation as a signal processing strategy for sensory perception and numerous mathematical models have been proposed; however, it remains unclear how the neural networks extract particular sources from a complex mixture of inputs. We discovered that neurons in cultures of dissociated rat cortical cells could learn to represent particular sources while filtering out other signals. Specifically, the distinct classes of neurons in the culture learned to respond to the distinct sources after repeating training stimulation. Moreover, the neural network structures changed to reduce free energy, as predicted by the free-energy principle, a candidate unified theory of learning and memory, and by Jaynes’ principle of maximum entropy. This implicit learning can only be explained by some form of Hebbian plasticity. These results are the first in vitro (as opposed to in silico) demonstration of neural networks performing blind source separation, and the first formal demonstration of neuronal self-organization under the free energy principle.     

Elbow flexor evoked twitch contractile properties in untrained men and women and male bodybuilders

The influence of elbow joint angle on elbow flexor isometric evoked twitch contractile properties was assessed in 15 young women (F), 18 young men (M) and 11 male bodybuilders (BB). Measurements were made at elbow joint angles of 1.31, 1.57, 1.83, 2.09, 2.36, 2.62 and 2.88 rad (3.14 rad =180° =full extension). The largest peak twitch torque values [mean (SE) N · m] in F [3.77 (0.20)], M [10.38 (0.68)] and BB [11.38 (1.05)] occurred at 2.88 rad. Peak torque was progressively smaller at smaller joint angles, but the decline from 2.88 to 1.31 rad was greater in M (68%) and BB (76%) than F (59%). Thus, the magnitude of intergroup differences in peak twitch torque (PT) was joint angle dependent. Twitch time to peak torque (TPT) was influenced in a complex way by joint angle in the three groups; BB had the lowest values at small joint angles but the highest values at the largest angles. Half-relaxation time (HRT) generally increased from the smallest to largest joint angles in a pattern that did not differ significantly among the three groups. Maximum rates of twitch torque development and relaxation showed the same pattern of results as PT; indicating that these time-related measures were more sensitive to joint angle effects on PT than on TPT or HRT. The results of this study indicate that careful consideration should be given to the selection of joint angles in the measurement of evoked twitch contractile properties for the purpose of making group comparisons or investigating the effects of interventions such as training.     

A wheat histone H3 promoter confers cell division-dependent and -independent expression of the gus A gene in transgenic rice plants

To investigate developmental regulation of wheat histone H3 gene expression, the H3 promoter, which has its upstream sequence to ?1711 (relative to the cap site as +1), was fused to the coding region of the gus A gene (?1711H3/GUS) and introduced into a monocot plant, rice. Detailed histochemical analysis revealed two distinct types of GUS expression in transgenic rice plants; one is cell division-dependent found in the apical meristem of shoots and roots and in young leaves, and another is cell division-independent detected in flower tissues including the anther wall and the pistil. In this study, replication-dependent expression occurring in non-dividing cells which undergo endoreduplication could not be discriminated from strict replication-independent expression. The observed expression pattern in different parts of roots suggested that the level of the H3/GUS gene expression is well correlated with activity of cell division in roots. To identify 5′ sequences of the H3 promoter necessary for an accurate regulation of the GUS expression, two constructs containing truncated promoters, ?908H3/GUS and ?185H3/GUS, were analyzed in transiently expressed protoplasts, stably transformed calli and transgenic plants. The results indicated that the region from ?909 to ?1711 contains the positive cis-acting element(s) and that the proximal promoter region (up to ?185) containing the conserved hexamer, octamer and nonamer motifs is sufficient to direct both cell division-dependent and -independent expression. The use of the meristem of roots regenerated from transformed calli for the analysis of cell division-dependent expression of plant genes is discussed.