How does the human visual system compare the speeds of spatially separated objects?

We measured psychophysical thresholds for discriminating the speeds of two arrays of moving dots. The arrays could be juxtaposed or could be spatially separated by up to 10 degrees of visual angle, eccentricity being held constant. We found that the precision of the judgments varied little with separation. Moreover, the function relating threshold to separation was similar whether the arrays moved in the same, in opposite or in orthogonal directions. And there was no significant difference in threshold whether the two stimuli were initially presented to the same cerebral hemisphere or to opposite ones. How are human observers able to compare stimuli that fall at well separated positions in the visual field? We consider two classes of explanation: (i) Observers' judgments might be based directly on the signals of dedicated 'comparator neurons', i.e. neurons drawing inputs of opposite sign from local regions of the visual field. (ii) Signals about local features might be transmitted to the site of comparison by a shared 'cerebral bus', where the same physical substrate carries different information from moment to moment. The minimal effects of proximity and direction (which might be expected to influence local detectors of relative motion), and the combinatorial explosion in the number of comparator neurons that would be required by (i), lead us to favor models of type (ii).

Reformation of the Electron Internal Transport Barrier with the Appearance of a Magnetic Island.

When realising future fusion reactors, their stationary burning must be maintained and the heat flux to the divertor must be reduced. This essentially requires a stationary internal transport barrier (ITB) plasma with a fast control system. However, the time scale for determining the position of the foot point of an ITB is not clearly understood even though its understanding is indispensable for fast profile control. In this study, the foot point of the electron ITB (eITB) was observed to be reformed at the vicinity of a magnetic island when the island started to form. In addition, the enhanced confinement region was observed to expand during the eITB formation according to the radial movement of the magnetic island toward the outer region. Compared to the time scales of the local heat transport, the faster time scales of the movement of the eITB foot point immediately after island formation (~0.5 ms) suggest the importance of the magnetic island for plasma profile control to maintain stationary burning.

A tuberculosis outbreak in a psychiatric hospital: Kanagawa, Japan, 2012.

In January 2012, an inpatient in a ward of a psychiatric hospital with nearly 300 beds in Kanagawa, Japan, was diagnosed with sputum smear-positive pulmonary tuberculosis (TB). Here we characterise the TB outbreak cases and identify the population at risk. TB was diagnosed when a person tested bacteriologically positive for TB or was determined to have TB by a physician. A latent TB infection (LTBI) case was defined as a person tested positive by interferon-gamma release assay (IGRA). A total of 125 contacts were screened via IGRA and chest X-ray. In all, 15 TB and 15 LTBI cases were found by the end of October 2012, and thereafter no additional TB case was found. Of the 15 TB cases, eight were culture-positive and all the isolates had identical variable number tandem repeat patterns. Twenty-four of the 56 (42.9%, 95% confidence interval (CI) 29.7-56.8) inpatients in the ward had either TB or LTBI with a relative risk of 8.6 (95% CI 1.2-59.3), compared to the staff members who did not work full-time in the ward (one of 20 (5.0%, 95% CI 0.0-24.9)). We recommend that psychiatric hospitals conduct periodic screening of staff members and inpatients for TB to prevent nosocomial TB outbreaks.

mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse.

The mechanism by which the cytosolic protein Zap70 physically interacts with and phosphorylates its substrate, the transmembrane protein LAT, upon T cell receptor (TCR) stimulation remains largely obscure. In this study, we found that the pharmacological inhibition of formins, a major class of actin nucleators, suppressed LAT phosphorylation by Zap70, despite TCR stimulation-dependent phosphorylation of Zap70 remaining intact. High-resolution imaging and three-dimensional image reconstruction revealed that localization of phosphorylated Zap70 to the immune synapse (IS) and subsequent LAT phosphorylation are critically dependent on formin-mediated actin polymerization. Using knockout mice, we identify mDia1 and mDia3, which are highly expressed in T cells and which localize to the IS upon TCR activation, as the critical formins mediating this process. Our findings therefore describe previously unsuspected roles for mDia1 and mDia3 in the spatiotemporal control of Zap70-dependent LAT phosphorylation at the IS through regulation of filamentous actin, and underscore their physiological importance in TCR signaling.

A distinct function of the retinoblastoma protein in the control of lipid composition identified by lipidomic profiling.

Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length. Consistently, we observed that Rb depletion increased the levels of fatty acids with the corresponding carbon chain length and number of carbon-carbon double bondssuch as myristic acid (14:0), palmitic acid (16:0), stearic acid (18:0) and all forms of FA 18:1. Microarray analysis revealed that Rb depletion induced significant upregulation of enzymes involved in elongation and desaturation of fatty acids. Among these, we found that elongation of long chain fatty acid family member 6 (Elovl6) and stearoyl-CoA desaturase 1 (Scd1) are the most robustly controlled by Rb possibly through E2F and sterol regulatory element-binding protein transcription factors. Depletion of Elovl6 or Scd1 significantly suppressed colony formation, sphere formation and xenograft tumor growth of Rb-deficient tumor cells. Suppression of self-renewal by the SCD1 inhibitor was rescued upon supplementation of the mono-unsaturated fatty acids generated by this enzyme. This study suggests a novel role for Rb in suppressing the malignant progression of tumors by controlling the lipid composition.

The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity.

Retinoblastoma (RB) protein inactivation during tumor progression is often associated with acquisition of immature phenotypes and resistance to therapy. Determination of an RB inactivation signature in a context of gaining undifferentiated phenotype in a p53-null sarcoma system revealed a critical role for interleukin (IL)-6. Using a Gene Set Enrichment Analysis (GSEA), we discovered that poorly differentiated breast cancers are enriched for this RB inactivation signature. Accelerated IL-6 secretion following RB inactivation in an RB-intact luminal-type breast cancer cell line MCF-7 promoted a positive feed forward loop between IL-6 and STAT3 driving tumor growth and endocrine therapy resistance. In addition, some of RB-intact basal-like type breast cancer cell lines exhibited a similar phenotype following RB depletion. The mechanism whereby RB inactivation increases IL-6 production in MCF-7 cells appeared to involve fatty acid oxidation (FAO)-dependent mitochondrial metabolism and c-Jun NH(2)-terminal kinase (JNK). In addition, IL-6, via STAT3-mediated feedback to mitochondria, autonomously adjusts mitochondrial superoxide to levels suitable to maintain stem cell-like activity. The gene expression profile of luminal-type breast cancer patients with low RB expression revealed high enrichment of genes involved in mitochondrial respiration and downstream targets of IL-6. These findings unveiled an unexpected strategy whereby RB suppresses malignant features of cancer cells through metabolic reprogramming and cell-autonomous inflammation.

Neonatal Kisspeptin is Steroid-Independently Required for Defeminisation and Peripubertal Kisspeptin-Induced Testosterone is Required for Masculinisation of the Brain: A Behavioural Study Using Kiss1 Knockout Rats.

Rodents show apparent sex differences in their sexual behaviours. The present study used Kiss1 knockout (KO) rats to evaluate the role of kisspeptin in the defeminisation/masculinisation of the brain mechanism that controls sexual behaviours. Castrated adult Kiss1 KO males treated with testosterone showed no male sexual behaviours but demonstrated the oestrogen-induced lordosis behaviours found in wild-type females. The sizes of some of the sexual dimorphic nuclei of Kiss1 KO male rats are similar to those of females. Plasma testosterone levels at embryonic day 18 and postnatal day 0 (PND0) in Kiss1 KO males were high, similar to wild-type males, indicating that perinatal testosterone is secreted in a kisspeptin-independent manner. Long-term exposure to testosterone from peripubertal to adult periods restored mounts and intromissions in KO males, suggesting that kisspeptin-dependent peripubertal testosterone secretion is required to masculinise the brain mechanism. This long-term testosterone treatment failed to abolish lordosis behaviours in KO males, whereas kisspeptin replacement at PND0 reduced lordosis quotients in Kiss1 KO males but not in KO females. These results suggest that kisspeptin itself is required to defeminise behaviour in the perinatal period, in cooperation with testosterone. Oestradiol benzoate treatment at PND0 suppressed lordosis quotients in Kiss1 KO rats, indicating that the mechanisms downstream of oestradiol work properly in the absence of kisspeptin. There was no significant difference in aromatase gene expression in the whole hypothalamus between Kiss1 KO and wild-type male rats at PND0. Taken together, the present study demonstrates that both perinatal kisspeptin and kisspeptin-independent testosterone are required for defeminisation of the brain, whereas kisspeptin-dependent testosterone during peripuberty to adulthood is needed for masculinisation of the brain in male rats.

Evaluation of the toxic activity of anorectic diethylpropion in Chinese hamster ovary cells.

Diethylpropion has been available in the market for treating obesity for over 50 years. Refined studies are lacking to fully elucidate its action spectrum. The aim of our study was to evaluate possible toxic effects of anorectic diethylpropion in Chinese hamster ovary (CHO) cells. Comet assay (detects breaks in the DNA strand), micronucleus test (detects clastogenic/aneugenic damage), and cell survival test (detects cytotoxic damage) were used to evaluate the toxic effects. In comet assay, we found that the damage scores with diethylpropion treatments at the concentrations of 20 and 40 µg/mL were more significant ( p < 0.05) than that of the negative control. When assessing the possible aneugenic and/or clastogenic damage caused by the drug in CHO cells, we found no difference ( p > 0.05) in the values of micronucleated cells when comparing different diethylpropion treatments and the negative control. Regarding the cell viability, for all the diethylpropion concentrations tested, higher values ( p < 0.05) of apoptosis were found compared with those of the negative control. In relation to the number of necrotic cells, no difference ( p > 0.05) was noted between the means of the three concentrations of diethylpropion evaluated and the negative control. In the experimental conditions, we conclude that diethylpropion has weak genotoxic and cytotoxic activities.

First measurement of time evolution of electron temperature profiles with Nd:YAG Thomson scattering system on Heliotron J.

A Nd:YAG Thomson scattering system has been developed for Heliotron J. The system consists of two 550 mJ 50 Hz lasers, large collection optics, and 25 radial channel (∼1 cm spatial resolution) interference polychromators. This measurement system achieves a S/N ratio of ∼50 for low-density plasma (ne ∼ 0.5 × 10(19) m(-3)). A time evolution of electron temperature profiles was measured with this system for a high-intensity gas-puff (HIGP) fueling neutral-beam-injection plasma. The peripheral temperature of the higher-density phase after HIGP recovers to the low-density pre-HIGP level, suggesting that improving particle transport in the HIGP plasma may be possible.

Prostacyclin promotes oligodendrocyte precursor recruitment and remyelination after spinal cord demyelination.

Adult oligodendrocyte precursor cells (OPCs) are located adjacent to demyelinated lesion and contribute to myelin repair. The crucial step in remyelination is the migration of OPCs to the demyelinated area; however, the mechanism of OPC migration remains to be fully elucidated. Here we show that prostacyclin (prostaglandin I2, PGI2) promotes OPC migration, thereby promoting remyelination and functional recovery in mice after demyelination induced by injecting lysophosphatidylcholine (LPC) into the spinal cord. Prostacyclin analogs enhanced OPC migration via a protein kinase A (PKA)-dependent mechanism, and prostacyclin synthase expression was increased in the spinal cord after LPC injection. Notably, pharmacological inhibition of prostacyclin receptor (IP receptor) impaired remyelination and motor recovery, whereas the administration of a prostacyclin analog promoted remyelination and motor recovery after LPC injection. Our results suggest that prostacyclin could be a key molecule for facilitating the migration of OPCs that are essential for repairing demyelinated areas, and it may be useful in treating disorders characterized by demyelination.

Persistence and metallic composition of paint particles in sediments from a tidal inlet.

Concentrations of Cu, Pb, Sn and Zn have been determined in sediment (<500 µm) and macroscopic paint particles (>500 µm) retrieved from sections of two cores collected from a tidal inlet of the Plym estuary, southwest England. Paint particles contributed up to about 0.2% of the total mass retrieved from each section and were most abundant towards the base of the cores where, according to (210)Pb dating, deposition took place about a decade prior to sampling. Metal concentrations in the paint particles pooled from the sections were highly variable, typically spanning two orders of magnitude in each core, and were greatest for Cu and Zn (up to 460,000 and 170,000 µg g(-1), respectively) due to their use in contemporary antifouling formulations applied to boat hulls. Concentrations of metals in the sediment were, however, relatively invariant, an effect attributed to the abundance and dispersion of microscopic paint particles throughout the cores.

Reversion-inducing cysteine-rich protein with Kazal motifs interferes with epidermal growth factor receptor signaling.

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene had been isolated as an antagonist to RAS signaling; however, the mechanism of its action is not clear. In this study, the effect of loss of RECK function was assessed in various ways and cell systems. Successive cell cultivation of mouse embryonic fibroblasts (MEFs) according to 3T3 protocol revealed that the germline knockout of RECK confers accelerated cell proliferation and early escape from cellular senescence associated with downregulation of p19(Arf), Trp53 and p21(Cdkn1a). In contrast, short hairpin RNA-mediated depletion of RECK induced irreversible growth arrest along with several features of the Arf, Trp53 and Cdkn1a-dependent cellular senescence. Within 2 days of RECK depletion, we observed a transient increase in protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation associated with an upregulated expression of cyclin D1, p19(Arf), Trp53, p21(Cdkn1a) and Sprouty 2. On further cultivation, RAS, AKT and ERK activities were then downregulated to a level lower than control, indicating that RECK depletion leads to a negative feedback to RAS signaling and subsequent cellular senescence. In addition, we observed that epidermal growth factor receptor (EGFR) activity was transiently upregulated by RECK depletion in MEFs, and continuously downregulated by RECK overexpression in colon cancer cells. These findings indicate that RECK is a novel modulator of EGFR signaling.

Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs.

Cancer cells show characteristic gene expression profiles. Recent studies support the potential importance of microRNA (miRNA) expression signatures as biomarkers and therapeutic targets. The membrane-anchored protease regulator RECK is downregulated in many cancers, and forced expression of RECK in tumor cells results in decreased malignancy in animal models. RECK is also essential for mammalian development. In this study, we found that RECK is a target of at least three groups of miRNAs (miR-15b/16, miR-21 and miR-372/373); that RECK mutants lacking the target sites for these miRNA show augmented tumor/metastasis-suppressor activities; and that miR-372/373 are upregulated in response to hypoxia through HIF1alpha and TWIST1, whereas miR-21 is upregulated by RAS/ERK signaling. These data indicate that the hypoxia- and RAS-signaling pathways converge on RECK through miRNAs, cooperatively downregulating this tumor suppressor and thereby promoting malignant cell behavior.

Valacyclovir neurotoxicity: clinical experience and review of the literature.

Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.(AU)

Genotoxic effect of Physalis angulata L. (Solanaceae) extract on human lymphocytes treated in vitro

Physalis angulata L (Solanaceae) is a medicinal plant from North of Brazil, whose different extracts and infusions are commonly used in the popular medicine for the treatment of malaria, asthma, hepatitis, dermatitis and rheumatism. However, the genotoxic effects of P. angulata on human cells is not well known. The main purpose of the present study was to evaluate the in vitro genotoxic effects of aqueous extract of P. angulata using the comet assay and the micronucleus assay in human lymphocytes provided from 6 healthy donors. Treatments with P. angulata extracts were performed in vitro in order to access the extent of DNA damage. The comet assay has shown that treatments with P. angulata at 0.5, 1.0, 2.0, 3.0 and 6.0 microg/mL in culture medium were genotoxic. Lymphocytes treated with P. angulata at the concentrations of 3.0 and 6.0 microg/mL in culture medium showed a statistically significant increase in the frequency of micronucleus (p<0.05), however, the cytokinesis blocked proliferation index (CBPI) was not decreased after P. angulata treatment. In conclusion, the present work demonstrated the genotoxic effects of P. angulata extract on human lymphocytes in vitro.

Ballast water: a review of the impact on the world public health

Since the nineteenth century ships have been using ballast water (BW) for safety, stability, propulsion and maneuverability, as well as to redress loss of fuel weight and water consumption, and to maintain structural stress at acceptable levels. Ballast water has been spreading many non-native species around the globe, but little is known about the extent and potential significance of ship-mediated transfer of microorganisms. The global movements of ballast water by ships create a long-distance dispersal mechanism for human pathogens that may be important in the worldwide distribution of microorganisms, as well as for the epidemiology of waterborne diseases. Only a few studies have been carried out on this subject, most of them involving ballast water containing crustacean larvae and phytoplankton. Specialized microbiological studies on these waters are necessary to avoid a repeat of what happened in 1991, when epidemic cholera was reported in Peru and rapidly spread through Latin America and Mexico. In July of 1992, Vibrio cholerae was found in the USA and the Food and Drug Administration (FDA) determined that it came from ballast water of ships whose last port of call was in South America. In Brazil, just a few studies about the subject have been performed. An exploratory study by the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária - ANVISA) found in ballast water different microorganisms, such as fecal coliforms, Escherichia coli, Enterococcus faecalis, Clostridium perfringens, coliphages, Vibrio cholerae O1 and Vibrio cholerae non-O1. Until now, Brazil has been focusing only on organisms transported to its territory from other countries by ballast water, to avoid their establishment and dissemination in Brazilian areas. Studies that can assess the probability that water ballast carries pathogenic microorganisms are extremely important, as is the examination of ships that arrive in the country. Treatment of the human...

Dental hygiene residential care in a 3-year dental hygiene education programme in Japan: towards dysphagia management based on the dental hygiene process of care.

This paper reports an evaluation of a residential care practice, which was part of a 'Dysphagia Management' course introduced into a 3-year dental hygiene curriculum in Japan. The clinical practice was performed at a care facility for the elderly people. Dental hygiene interventions, which consisted mainly of professional oral care, were implemented on a client who was bed-bound after suffering from a stroke. As the client had severe tension in muscles around oral cavity, it was difficult for the facility care workers to provide daily oral hygiene care. The goals of the dental hygiene care plan included decreasing tension of oral muscles and reducing periodontal inflammation and halitosis. The dental hygiene interventions were given once a month for 5 months. Evaluation in the fifth month demonstrated relaxation of oral muscles, decrease in plaque accumulation, and improvements in levels of gingival inflammation, indicating the partial achievements of the initial goals. Possibilities for revision of the care plan could call for more active involvement of the facility care workers and client-centered goal setting. This learning experience provided an opportunity for continuing intervention and evaluation of dental hygiene care for the same client. The positive results of our limited interventions further confirmed the importance of professional oral care in organic and functional improvements in oral health for the elderly people.

Experimental evidence of a zonal magnetic field in a toroidal plasma.

A zonal magnetic field is found in a toroidal plasma. The magnetic field has a symmetric bandlike structure, which is uniform in the toroidal and poloidal directions and varies radially with a finite wavelength of mesoscale, which is analogous to zonal flows. A time-dependent bicoherence analysis reveals that the magnetic field should be generated by the background plasma turbulence. The discovery is classified as a new kind of phenomenon of structured magnetic field generation, giving insight into phenomena such as dipole field generation in rotational planets.

Calculated electronic structures and Néel temperatures of half-metallic diluted antiferromagnetic semiconductors.

The possibility of half-metallic diluted antiferromagnetic semiconductors of II-VI compounds is investigated on the basis of first-principles electronic structure calculation. The electronic structures of ZnS, ZnSe, ZnO, CdS and CdSe doped with two kinds of 3d transition metal ions are calculated using the Korringa-Kohn-Rostoker (KKR) method and their magnetic transition temperatures are determined using a cluster-type approximation. It is predicted that II-VI compound semiconductors doped with two kinds of magnetic ions might be good candidates for half-metallic antiferromagnets.