Dopamine and inhibitory action control: evidence from spontaneous eye blink rates

The inhibitory control of actions has been claimed to rely on dopaminergic pathways. Given that this hypothesis is mainly based on patient and drug studies, some authors have questioned its validity and suggested that beneficial effects of dopaminergic stimulants on response inhibition may be limited to cases of suboptimal inhibitory functioning. We present evidence that, in carefully selected healthy adults, spontaneous eyeblink rate, a marker of central dopaminergic functioning, reliably predicts the efficiency in inhibiting unwanted action tendencies in a stop-signal task. These findings support the assumption of a modulatory role for dopamine in inhibitory action control.

Randomizing visual feedback in manual aiming: reminiscence of the previous trial condition and prior knowledge of feedback availability

A trial-by-trial analysis was used to systematically examine the influence of switching visual conditions on visual feedback utilization for a manual aiming movement. In experiment one, vision was randomly manipulated from trial to trial with no more than four consecutive trials in the same visual condition. In experiment two, participants were provided with certainty of visual feedback availability prior to every trial. Results of both studies revealed that movement endpoint variability was most associated with visual feedback availability on the previous trial. Furthermore, correlation analyses comparing movement trajectory at 25, 50 and 75% with movement end (i.e. 100%) revealed that the efficiency of online corrections also depends on the availability of visual feedback on the previous trial. These results suggest that the accuracy of an aiming movement is highly dependent on processing of offline visual information from the preceding trial. This study was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) awarded to Luc Tremblay.

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RNA interference inhibits yellow fever virus replication in vitro and in vivo

RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.

Physician challenges in communicating bad news

Communicating bad news is never easy and for physicians these interactions may be a significant source of stress. To examine the characteristics that make delivering of bad news stressful, two studies were conducted. In the first study, 37 physicians generated 192 responses describing the characteristics that influence how difficult it is to break bad news. After sorting the responses in terms of common themes, six categories were identified: Physician, Patient, Institutional, Illness, Relationship, and Mishap. In Study 2, 115 physicians rated the degree of stress associated with each factor. Using principle component and reliability analyses, empirical support was found for six categories. A higher-order factor analysis suggested the existence of one over-arching factor. Items in the Mishap category were rated on average as the most stressful. Stress scores were largely unrelated to years in practice, experience delivering bad news or training.

Effects of Thrombosed Vena Cava Filters on Blood Flow: Flow Visualization and Numerical Modeling

Inferior vena cava (IVC) filters are used to prevent pulmonary embolism (PE) in patients with deep vein thrombosis for whom anticoagulation is contraindicated. IVC filters have been shown to be effective in trapping embolized clots and preventing PE; however, among the commercially available designs, the optimal balance of clot capture efficiency, clot dissolution, and prevention of to vena cava occlusion is unknown. Clot capture efficiency has been quantified in numerous in vitro studies, in which model clots are released into a mock circulation system, with the relative capture efficiency of various IVC filters analyzed statistically. In general, two-stage filters have been found to be more efficient than one-stage filters. However, other factors may play a role in the ultimate dissolution of clots and in the overall effect of the resulting blood flow on caval vasculature. Clot dissolution has been shown to increase with increasing wall shear stress, while low and oscillating wall shear stresses are known to have a deleterious effect on vessel walls, causing intimal hyperplasia. This paper describes the effect of IVC filters on blood flow, velocity patterns, and wall shear stress by flow visualization and computational fluid dynamics.

High genetic diversity of Sappinia-like strains (Amoebozoa, Thecamoebidae) revealed by SSU rRNA investigations

Sappinia diploidea is known as a free-living amoeba of worldwide distribution and has also been reported as causative agent of a brain infection in an immunocompetent young man. In the current study, we were able to isolate eight strains of S. diploidea-like amoebae identified by light microscopy from different habitats. Cultures of all strains were established successfully for molecular characterization. The small subunit ribosomal RNA genes of all strains were sequenced and compared to one another, to the neotype of S. diploidea, and to strains of Sappinia pedata, the only other Sappinia species known to date, from GenBank by multiple sequence alignment and cluster analysis. Altogether, the phylogenetic position of the genus Sappinia within the Thecamoebidae was corroborated; however, it was shown that the genus splits into several well-separated clusters making the establishment of new species within this genus inevitable. Furthermore, two of the S. diploidea-like strains were actually more closely related to S. pedata than to S. diploidea, although the diagnostically relevant standing form which seems to be characteristic for S. pedata was not observed in either of the two strains. Claudia Wylezich and Julia Walochnik have contributed equally to this work.

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Working memory capacity,intelligence, and the magnitude of the attentional blink revisited

The attentional blink (AB) is a well-established phenomenon in the study of attention. This deficit in reporting the second of two targets presented in rapid serial visual presentation when it occurs 200–500 ms after the first is considered to reflect a fundamental limitation in attentional processing. However, we recently reported that some individuals do not show an AB, and presented psychophysiological evidence that target processing differs between blinkers and non-blinkers. One possibility is that non-blinkers may have a larger WM capacity, allowing better attentional control. Here we explore the relation between the magnitude of the AB, general intelligence, and different measures of working memory (WM) and short-term memory (STM) capacity. Surprisingly, no correlation was found between memory capacity measures and AB magnitude, raising doubts about the generalizability of earlier findings of such a relationship.

Combining Nonlinear Biometric and Psychometric Models of Cognitive Abilities

It is well-established that genetic factors account for large proportions of individual differences in multiple cognitive abilities. It is also well-established that individual differences in performance on many different cognitive ability measures are strongly correlated. Recent empirical investigations, however, have suggested two interesting qualifications to these well-established findings: Genetic variance in cognitive abilities is higher in richer home environments (gene-by-environment interaction), and common variance in different cognitive abilities is lower at higher levels of overall ability (nonlinear factor structure). Although they have been investigated independently, these two phenomena may interact, because richer environments are routinely associated with higher ability levels. Using simulation we demonstrate how un-modeled nonlinear factor structure can obscure interpretation of gene-by-environment interaction. We then reanalyze data from the National Collaborative Perinatal Project, previously used by Turkheimer et al. (2003; Psychol Science), with a two-step method to model both phenomena.

Computational Modeling and Real-Time Control of Patient-Specific Laser Treatment of Cancer

An adaptive feedback control system is presented which employs a computational model of bioheat transfer in living tissue to guide, in real-time, laser treatments of prostate cancer monitored by magnetic resonance thermal imaging. The system is built on what can be referred to as cyberinfrastructure—a complex structure of high-speed network, large-scale parallel computing devices, laser optics, imaging, visualizations, inverse-analysis algorithms, mesh generation, and control systems that guide laser therapy to optimally control the ablation of cancerous tissue. The computational system has been successfully tested on in vivo, canine prostate. Over the course of an 18 min laser-induced thermal therapy performed at M.D. Anderson Cancer Center (MDACC) in Houston, Texas, the computational models were calibrated to intra-operative real-time thermal imaging treatment data and the calibrated models controlled the bioheat transfer to within 5 °C of the predetermined treatment plan. The computational arena is in Austin, Texas and managed at the Institute for Computational Engineering and Sciences (ICES). The system is designed to control the bioheat transfer remotely while simultaneously providing real-time remote visualization of the on-going treatment. Post-operative histology of the canine prostate reveal that the damage region was within the targeted 1.2 cm diameter treatment objective.

Evidence for an attentional component in saccadic inhibition of return

After presentation of a peripheral cue, facilitation at the cued location is followed by inhibition of return (IOR). It has been recently proposed that IOR may originate at different processing stages for manual and ocular responses, with manual IOR resulting from inhibited attentional orienting, and ocular IOR resulting form inhibited motor preparation. Contrary to this interpretation, we found an effect of target contrast on saccadic IOR. The effect of contrast decreased with increasing reaction times (RTs) for saccades, but not for manual key-press responses. This may have masked the effect of contrast on IOR with saccades in previous studies (Hunt and Kingstone in J Exp Psychol Hum Percept Perform 29:1068–1074, 2003) because only mean RTs were considered. We also found that background luminance strongly influenced the effects of gap and target contrast on IOR.

Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice

Galectins have recently emerged as central regulators of the immune system. We have previously demonstrated that carbohydrate-dependent binding of galectin-2 induces apoptosis in activated T cells. Here, we investigate the potential therapeutic effect of galectin-2 in experimental colitis. Galectin-2 expression and its binding profile were determined by immunohistochemistry. Acute and chronic colitis was induced by dextran sodium sulfate administration and in a T-cell transfer colitis model. Apoptosis was assessed by TdT-mediated dUTP-biotin nick-end labeling, and cytokine secretion was determined by cytometric bead array. We show that galectin-2 was constitutively expressed mainly in the epithelial compartment of the mouse intestine and bind to lamina propria mononuclear cells. During colitis, galectin-2 expression was reduced, but could be restored to normal levels by immunosuppressive treatment. Galectin-2 treatment induced apoptosis of mucosal T cells and thus ameliorated acute and chronic dextran-sodium-sulfate-induced colitis and in a T-helper-cell 1-driven model of antigen-specific transfer colitis. Furthermore, the pro-inflammatory cytokine release was inhibited by galectin-2 treatment. In preliminary toxicity studies, galectin-2 was well tolerated. Our study provides evidence that galectin-2 induces apoptosis in vivo and ameliorates acute and chronic murine colitis. Furthermore, galectin-2 has no significant toxicity over a broad dose range, suggesting that it may serve as a new therapeutic agent in the treatment of inflammatory bowel disease.

Methodological problems undermine tests of the ideo-motor conjecture

Recent behavioural research has investigated whether viewing someone perform an action results in activation of that action by the observer. Postulated empirical support for this ‘ideo-motor (IM) conjecture’ typically rests upon two types of experimental paradigm (reaction time and movement tracking tasks). These paradigms purport to show movement facilitation when compatible movements are observed and vice versa, but only for biological stimuli. Unfortunately, these paradigms often contain confounding (and unavoidable) generic stimulus–response compatibility effects that are not restricted to observed human movement. The current study demonstrates in three experiments that equivalent compatibility effects can be produced by non-biological stimuli. These results suggest that existing empirical paradigms may not, and perhaps cannot, support the IM-conjecture.

RNAi-dependent and -independent antiviral phenotypes of chromosomally integrated shRNA clones: Role of VASP in respiratory syncytial virus growth

Stable RNA interference (RNAi) is commonly achieved by recombinant expression of short hairpin RNA (shRNA). To generate virus-resistant cell lines, we cloned a shRNA cassette against the phosphoprotein gene of respiratory syncytial virus (RSV) into a polIII-driven plasmid vector. Analysis of individual stable transfectants showed a spectrum of RSV resistance correlating with the levels of shRNA expressed from different chromosomal locations. Interestingly, resistance in a minority of clones was due to mono-allelic disruption of the cellular gene for vasodilator-stimulated phosphoprotein (VASP). Thus, pure clones of chromosomally integrated DNA-directed RNAi can exhibit gene disruption phenotypes resembling but unrelated to RNAi.

Postural costs of performing cognitive tasks in non-coincident reference frames

Dual-task interactions in posture and cognitive tasks have been explained as a competition for spatial processing structures or as interference in the online sensorimotor adjustments required for sensory integration. Going beyond these general terms accounts, we propose that interference between spatial and temporal operations in posture–cognition arises at least partly from the need to share a common behavioral context, such as a spatial frame of reference. Using immersive visualization and motion-tracking techniques, we manipulated the spatial reference frames for a standing task and a conjunction visual search task into or out of coincidence. Aside from performance trade-offs due to task-load manipulations, performing visual search in a non-coincident reference frame led to cognitive task and postural task performance decrements (Experiment 1). Postural dual-task decrements were also observed when visual search was split between coincident and non-coincident frames and both frame conditions rendered identical in visual information relevant to posture control (Experiment 2). We concluded that the postural control costs observed for posture–cognition dual-tasking may in part reflect costs of keeping tasks’ reference frames in register.

Spontaneous reactions to health risk feedback: a network perspective

Research on the reception of health risk feedback has focused on the analysis of single, researcher-selected cognitive reactions. The full range of spontaneous reactions and their patterns have received little attention. The present paper explores content, interrelations, and adaptivity of spontaneous reactions to health risk feedback from a network perspective. Participants (n = 423) received blood pressure and cholesterol feedback and listed their thoughts afterwards. A network of reactions to health risk feedback was constructed from the responses. Emotions, risk feedback valence, future lifestyle, and expectedness emerged as strong and largely well-connected network nodes, while previously well-researched reactions like feedback acceptance formed small, less connected nodes. The majority of reaction patterns identified through the network appeared adaptive, even after negative feedback. The network provides a potentially useful tool for research and practice, highlighting previously neglected relevant reactions, and providing a group-level background against which individual reactions can be evaluated.

Application of Whole Mouse Embryo Culture System on Stem Cell Research

The normal development of mouse embryo in vivo could be maintained in vitro up to 72 h in the presence of rat serum which is continuously supplied with the appropriate concentration of O₂ and CO₂. There are several applications of the whole mouse embryo culture model for study of cellular dynamics in hematopoiesis and its interaction with vasculogenesis. In this protocol, we have described details of manipulation techniques in combination with the whole embryo culture and also some advance techniques applied to the mouse embryo such as intra-cardiac inoculation of acetylated low density lipoprotein for cell-specific labeling and engraftment of donor yolk-sac from different genotype/phenotype mouse embryo onto the yolk-sac of host mouse for study of the dynamic distribution of hematopoietic cell.

Estimation of Breathing Rate from Respiratory Sinus Arrhythmia: Comparison of Various Methods

Although respiratory sinus arrhythmia (RSA) is a well-known and often studied phenomenon, methods to estimate (average) respiratory rate from heart rate variability via RSA have been investigated and published only sparsely. We reinvestigate three published techniques and contrast them to our own approaches. All methods were also evaluated for respiration signals to yield approximations of the true breathing rate for comparison. Our analyses are based on physiological recordings available at PhysioNet, an online database. Results show that the RSA of young supine subjects yields good approximations of mean respiratory rate in the case of time series longer than 1 min, while the estimations become noticeably less accurate for elderly persons. Our own “advanced counting method” produced the best results, and in addition principally permits even the definition of instantaneous respiratory rates. Consequently, it is recommended for further investigations.

Physical inactivity and cognitive functioning: results from bed rest studies

In addition to multiple health benefits, participation in physical activity can enhance cognitive functioning. Less clear is how reducing physical activity levels affects cognition, an issue potentially addressed by bed rest studies having included cognitive tests. Detailed and reviewed here are 17 such studies, featuring 251 subjects, bed rest for 7–70 days, and tests of cognition ranging from reaction time to executive functions. The reported effects of bed rest on cognitive performance vary considerably, from a generally expected worsening to an improvement. Practice effects could be implicated in the performance improvements, and reports of worsening are often of limited interpretability or the results were not replicated. Any cognitive effects of bed rest thus remain to be established. Detrimental effects could influence the in-progress plans for human spaceflights to Mars (simulated by bed rest), and have implications for medical conditions promoting inactivity and lifestyles that are largely sedentary.

Saccadic inhibition underlies the remote distractor effect

The remote distractor effect is a robust finding whereby a saccade to a lateralised visual target is delayed by the simultaneous, or near simultaneous, onset of a distractor in the opposite hemifield. Saccadic inhibition is a more recently discovered phenomenon whereby a transient change to the scene during a visual task induces a depression in saccadic frequency beginning within 70 ms, and maximal around 90–100 ms. We assessed whether saccadic inhibition is responsible for the increase in saccadic latency induced by remote distractors. Participants performed a simple saccadic task in which the delay between target and distractor was varied between 0, 25, 50, 100 and 150 ms. Examination of the distributions of saccadic latencies showed that each distractor produced a discrete dip in saccadic frequency, time-locked to distractor onset, conforming closely to the character of saccadic inhibition. We conclude that saccadic inhibition underlies the remote distractor effect.

Does the semantic activation of quantity representations influence motor parameters?

In size and parity judgment tasks, we investigated whether the activation of numerical quantity exerts an influence on motor response parameters such as response force. Results showed typically strong effects on reaction time of numerical distance in the size judgment task (Experiments 1 and 2) and SNARC-compatibility (Experiment 1) in both tasks, indicating that semantic quantity representations were activated. Response force, however, varied at most weakly with the numerical magnitudes of the digits. Our results place limits on previously suggested interconnections of the magnitude and response systems. Activations within the magnitude system seem to have a strong influence on the initiation and selection of which action to produce, but only a little influence on the dynamics of response production (i.e., response execution).