Blinking suppresses the neural response to unchanging retinal stimulation

Blinks profoundly interrupt visual input but are rarely noticed, perhaps because of blink suppression, a visual-sensitivity loss that begins immediately prior to blink onset. Blink suppression is thought to result from an extra-retinal signal that is associated with the blink motor command and may act to attenuate the sensory consequences of the motor action. However, the neural mechanisms underlying this phenomenon remain unclear. They are challenging to study because any brain-activity changes resulting from an extra-retinal signal associated with the blink motor command are potentially masked by profound neural-activity changes caused by the retinal-illumination reduction that results from occlusion of the pupil by the eyelid. Here, we distinguished direct top-down effects of blink-associated motor signals on cortical activity from purely mechanical or optical effects of blinking on visual input by combining pupil-independent retinal stimulation with functional MRI (fMRI) in humans. Even though retinal illumination was kept constant during blinks, we found that blinking nevertheless suppressed activity in visual cortex and in areas of parietal and prefrontal cortex previously associated with awareness of environmental change. Our findings demonstrate active top-down modulation of visual processing during blinking, suggesting a possible mechanism by which blinks go unnoticed.     

Wattled Curassows in Bolivia: abundance,habitat use,and conservation status

ABSTRACT The Wattled Curassow (Crax globulosa) is a globally threatened species restricted to humid várzea forest (seasonally flooded forest along white‐water rivers) in low‐lying regions of Amazonia. The Wattled Curassow were thought to have been extirpated from the Beni area of Bolivia, but were rediscovered near the Río Negro River in 2001. Our objectives were to determine the size of this population, examine habitat use, and based on our results, assess the conservation status of the Wattled Curassow. During July and August 2006, we used distance sampling to estimate the population density in our study area. We estimated the density of Wattled Curassows at 3.4 (95% CI: 1.4–8.1) individuals/km² and all were observed within 300 m of the river. Based on the availability of suitable habitat (18 km² of riparian várzea habitat within 300 m of the river), we estimated that the breeding population of Wattled Curassows in our study area consisted of 61 individuals. The specialized habitat requirements of the Wattled Curassow has important conservation implications because previous population estimates were based on the availability of várzea forest rather than the availability of water edge habitat within várzea forest. As a result, the current global population estimate (2500–9999) is higher than our estimate (500–2500) that takes the specialized habitat requirements of the Wattled Curassow into account. Given this low estimated population, along with the severely fragmented state of the few remaining populations and their dependence on a specialized and vulnerable habitat, we recommend that the status of the Wattled Curassow be upgraded from Vulnerable to Endangered.     

Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice

Background

Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice.

Methods

Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment.

Results

Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis.

Conclusions

Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.     

Studies on the cytotoxicity of cucurbitacins isolated from Cayaponia racemosa (Cucurbitaceae)

The cytotoxic potential of three cucurbitacins, 2,3,16,20(R),25-pentahydroxy-11,22-dioxo-cucurbita-5-en (cucurbitacin P, 1), 2,3,16,20(R),25-pentahydroxy-22-oxocucurbita-5-en (2) and 2,3,16,20(R),25-pentahydroxy-22-oxocucurbita-5,23(E)-diene (deacetylpicracin, 3), obtained from Cayaponia racemosa was evaluated as their ability to induce brine shrimp lethality, to inhibit the development of sea urchin eggs and tumor cell proliferation, and to lysis mouse erythrocytes. Compounds 1 and 2 were highly toxic with LC50 of (29.6+/-.1) (56.8) and (38.8 +/-.0) (76.6) micro/mL (umicro), respectively, while compound 3 was not effective at the tested concentrations. All tested compounds possessed an inhibitory effect on the proliferation of tumor cell lines, compound 1 being the most active, followed by 2 and 3. Nevertheless, no hemolytic activity or inhibition of the development of sea urchin eggs was observed for these compounds.     

Increased levels of osteopontin in sputum supernatant of smoking asthmatics

Smoking may modify the inflammatory pattern of the asthmatic airways. Osteopontin (OPN) has been associated with inflammation and fibrosis. In asthma, sputum levels of OPN are elevated and have been related to the underlying severity and to mediators expressing remodeling and inflammation.To evaluate the levels of OPN in sputum supernatants of asthmatic patients and to investigate the possible role of smoking as well as associations with mediators and cells involved in the inflammatory and remodeling process.We studied 103 asthma patients (49 smokers) and 40 healthy subjects (20 smokers) who underwent lung function tests, bronchial hyperresponsiveness to methacholine, and sputum induction for cell count identification and measurement of OPN, TGF-β1, IL-8, IL-13 and ECP in sputum supernatants. The concentrations of all mediators were measured using enzyme immunoassays.OPN levels (pg/ml) were significantly higher in smoking asthmatics compared to non-smoking asthmatics, and both non-smoking and smoking controls [median (interquartile ranges) 1120 (651, 1817) vs. 197 (118, 341) vs. 50 (42, 70) vs. 102 (77, 110) pg/ml, respectively; p < 0.001]. Regression analysis provided significant associations between OPN and sputum neutrophils, IL-8 and TGF-β1, the most significant being the one with TGF-β1. These associations were present only in smoking asthmatics.Smoking habit significantly affects sputum OPN levels in asthma. The associations of OPN with sputum neutrophils, TGF-β1 and IL-8 in smoking asthmatics suggest a possible role for OPN in the neutrophilic inflammation and remodeling process in this phenotype of asthma.     

Methods and approaches for the management of arthropod border incursions

Biological invasions are increasing and are strongly associated with negative agricultural, economic and ecological impacts. It is increasingly recognized that the primary focus in minimizing biological invasions should be to prevent initial entry of alien species. However, exclusion of terrestrial arthropods such as insects and mites is difficult, in part because of their relatively small size, cryptic habits, broad physiological tolerances and close association with various internationally traded goods. Here we discuss methods, approaches, management and intervention systems used by border biosecurity agencies to prevent entry of inadvertently transported arthropods. We examine the at-border systems that exist for the detection and identification of and response to alien arthropods, and discuss the constraints and challenges present in these systems. We critically review current border biosecurity systems and discuss their relative efficacy. We then discuss additional measures and key areas that could be addressed that may further improve these systems. These include: (1) the application of appropriate sampling strategies; (2) employment of suitable inspection methods adequate to detect small and hidden arthropods; and (3) thorough recording of methods, organisms detected and both negative and positive results of inspections. We emphasize that more research is needed on taxonomy, biology, genetics, distribution, host and disease associations, impacts and pathways of introductions for invasive arthropods. Of critical importance is the compilation of complete and accurate invasive species lists and high-risk species watch-lists. The adoption of these recommendations will contribute to improved biosecurity systems for the exclusion of alien, invasive and pest arthropods.     

The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines,sphingolipids and bile acids in the liver of C57BL/6 mice

Calorie restriction (CR) remains the most robust intervention to extend lifespan and improve health span. Using a global mass spectrometry‐based metabolomic approach, we identified 193 metabolites that were significantly differentially expressed (SDE) in the livers of C57BL/6 mice, fed graded levels of CR (10, 20, 30 and 40% CR) compared to mice fed ad libitum for 12 h a day. The differential expression of metabolites also varied with the different feeding groups. Pathway analysis revealed that graded CR had an impact on carnitine synthesis and the carnitine shuttle pathway, sphingosine‐1‐phosphate (S1P) signalling and methionine metabolism. S1P, sphingomyelin and L‐carnitine were negatively correlated with body mass, leptin, insulin‐like growth factor‐ 1 (IGF‐1) and major urinary proteins (MUPs). In addition, metabolites which showed a graded effect, such as ceramide, S1P, taurocholic acid and L‐carnitine, responded in the opposite direction to previously observed age‐related changes. We suggest that the modulation of this set of metabolites may improve liver processes involved in energy release from fatty acids. S1P also negatively correlated with catalase activity and body temperature, and positively correlated with food anticipatory activity. Injecting mice with S1P or an S1P receptor 1 agonist did not precipitate changes in body temperature, physical activity or food intake suggesting that these correlations were not causal relationships.     

Systematic review of the empirical evidence of study publication bias and outcome reporting bias

Background

The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention.

Methodology/Principal Findings

We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40–62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies.

Conclusions

Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.