F-actin flashes on phagosomes mechanically deform contents for efficient digestion in macrophages.

The mechanism and role of transient F-actin recruitment, or F-actin 'flashes', on phagosomes remains enigmatic. Here we provide a comprehensive characterization of F-actin flashing dynamics on phagosomes, including receptor and signaling involvement. F-actin flashes predominate during the integrin-driven complement receptor (CR)-mediated phagocytosis. F-actin flashes begin shortly after internalization and persist on phagosomes for approximately 3 minutes before disassembling and reassembling several times within the first hour. Strikingly, the appearance of F-actin flashes on phagosomes coincides with morphological deformation, lysis and occasional fission of internalized red blood cells. The cadence of flashes depends on particle stiffness, and the F-actin networks on phagosomes are enriched in mechanosensitive components including focal adhesion proteins, RhoA and actomyosin. Inhibiting Arp2/3 and myosin IIA activity significantly reduces the frequency at which phagosome cargo becomes deformed during transient F-actin accumulation. At later time points, post-F-actin flashing, enhanced degradation of phagosome contents is observed, compared with non-flashing phagosomes. Taken together, these data suggest that actomyosin-driven phagosome contractions serve to disrupt malleable particles physically, a process akin to mastication, to enhance later enzymatic digestion.

The probability of object-scene co-occurrence influences object identification processes.

Contextual information allows the human brain to make predictions about the identity of objects that might be seen and irregularities between an object and its background slow down perception and identification processes. Bar and colleagues modeled the mechanisms underlying this beneficial effect suggesting that the brain stocks information about the statistical regularities of object and scene co-occurrence. Their model suggests that these recurring regularities could be conceptualized along a continuum in which the probability of seeing an object within a given scene can be high (probable condition), moderate (improbable condition) or null (impossible condition). In the present experiment, we propose to disentangle the electrophysiological correlates of these context effects by directly comparing object-scene pairs found along this continuum. We recorded the event-related potentials of 30 healthy participants (18-34 years old) and analyzed their brain activity in three time windows associated with context effects. We observed anterior negativities between 250 and 500 ms after object onset for the improbable and impossible conditions (improbable more negative than impossible) compared to the probable condition as well as a parieto-occipital positivity (improbable more positive than impossible). The brain may use different processing pathways to identify objects depending on whether the probability of co-occurrence with the scene is moderate (rely more on top-down effects) or null (rely more on bottom-up influences). The posterior positivity could index error monitoring aimed to ensure that no false information is integrated into mental representations of the world.

Chlamydia trachomatis Inclusion Disrupts Host Cell Cytokinesis to Enhance Its Growth in Multinuclear Cells.

Chlamydia trachomatis, the leading cause of bacterial sexually transmitted infections, disrupts cytokinesis and causes significant multinucleation in host cells. Here, we demonstrate that multinuclear cells that result from unsuccessful cell division contain significantly higher Golgi content, an important source of lipids for chlamydiae. Using immunofluorescence and fluorescent live cell imaging, we show that C. trachomatis in multinuclear cells indeed intercept Golgi-derived lipid faster than in mononuclear cells. Moreover, multinuclear cells enhance C. trachomatis inclusion growth and infectious particle formation. Together, these results indicate that C. trachomatis robustly position inclusions to the cell equator to disrupt host cell division in order to acquire host Golgi-derived lipids more quickly in multinucleated progeny cells.

Missing links: testing the completeness of host-parasite checklists.

Host-parasite checklists are essential resources in ecological parasitology, and are regularly used as sources of data in comparative studies of parasite species richness across host species, or of host specificity among parasite species. However, checklists are only useful datasets if they are relatively complete, that is, close to capturing all host-parasite associations occurring in a particular region. Here, we use three approaches to assess the completeness of 25 checklists of metazoan parasites in vertebrate hosts from various geographic regions. First, treating checklists as interaction networks between a set of parasite species and a set of host species, we identify networks with a greater connectance (proportion of realized host-parasite associations) than expected for their size. Second, assuming that the cumulative rise over time in the number of known host-parasite associations in a region tends toward an asymptote as their discovery progresses, we attempt to extrapolate the estimated total number of existing associations. Third, we test for a positive correlation between the number of published reports mentioning an association and the time since its first record, which is expected because observing and reporting host-parasite associations are frequency-dependent processes. Overall, no checklist fared well in all three tests, and only three of 25 passed two of the tests. These results suggest that most checklists, despite being useful syntheses of regional host-parasite associations, cannot be used as reliable sources of data for comparative analyses.

Colonization of the Mediterranean basin by the vector biting midge species Culicoides imicola: an old story.

Understanding the demographic history and genetic make-up of colonizing species is critical for inferring population sources and colonization routes. This is of main interest for designing accurate control measures in areas newly colonized by vector species of economically important pathogens. The biting midge Culicoides imicola is a major vector of orbiviruses to livestock. Historically, the distribution of this species was limited to the Afrotropical region. Entomological surveys first revealed the presence of C. imicola in the south of the Mediterranean basin by the 1970s. Following recurrent reports of massive bluetongue outbreaks since the 1990s, the presence of the species was confirmed in northern areas. In this study, we addressed the chronology and processes of C. imicola colonization in the Mediterranean basin. We characterized the genetic structure of its populations across Mediterranean and African regions using both mitochondrial and nuclear markers, and combined phylogeographical analyses with population genetics and approximate Bayesian computation. We found a west/east genetic differentiation between populations, occurring both within Africa and within the Mediterranean basin. We demonstrated that three of these groups had experienced demographic expansions in the Pleistocene, probably because of climate changes during this period. Finally, we showed that C. imicola could have colonized the Mediterranean basin in the Late Pleistocene or Early Holocene through a single event of introduction; however, we cannot exclude the hypothesis involving two routes of colonization. Thus, the recent bluetongue outbreaks are not linked to C. imicola colonization event, but rather to biological changes in the vector or the virus.

Manipulability agreement as a predictor of action initiation latency.

In the domain of cognition, an increasing number of researchers are interested in the role of objects' motor affordances in cognitive processing. However, outside of the existing norms on the objects' levels of manipulability (e.g., Magnié, Besson, Poncet, & Dolisi, Journal of Clinical and Experimental Neuropsychology, 25:521-560,2003), relatively few norms exist that would allow researchers to have good control over objects' motor dimensions. In the present study, we have provided norms on the extent to which participants agreed about the movements typically performed for using specific objects--what we will call manipulability agreement. We showed that manipulability agreement was a good predictor of the times needed to initiate the action associated with the object. This study provides ratings on a new dimension of objects' motor affordances that could be useful to researchers in the domain of visual cognition.

Four types of manipulability ratings and naming latencies for a set of 560 photographs of objects.

The role of objects' motor affordances in cognition is a topic that has gained in popularity over the last decades. However, few studies exist that have normed the different motor dimensions of the objects; this limits researchers regarding usable stimuli, as well as comparability between studies. In the present study, we normed a set of 560 objects on four motor dimensions: the ease with which they can be grasped, moved, and pantomimed and the number of actions they afford. We then examined whether these four dimensions predict objects' naming latency. We believe that these norms will allow researchers interested in the role of motor affordances to have a better control over the dimensions they want to manipulate.

Do reward-processing deficits in schizophrenia-spectrum disorders promote cannabis use? An investigation of physiological response to natural rewards and drug cues.

BACKGROUND: Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use. METHODS: We divided a group of patients with SSD and nonpsychotic controls into cannabis users and nonusers. Response to emotional and cannabis-associated visual stimuli was assessed using self-report, event-related potentials (using the late positive potential [LPP]), facial electromyography and skin-conductance response. RESULTS: Our sample comprised 35 patients with SSD and 35 nonpsychotic controls. Compared with controls, the patients with SSD showed blunted LPP response to pleasant stimuli (p = 0.003). Across measures, cannabis-using controls showed greater response to pleasant stimuli than to cannabis stimuli whereas cannabis-using patients showed little bias toward pleasant stimuli. Reduced LPP response to pleasant stimuli was predictive of more frequent subsequent cannabis use (ß = -0.24, p = 0.034). LIMITATIONS: It is not clear if the deficit associated with cannabis use is specific to rewarding stimuli or nonspecific to any kind of emotionally salient stimuli. CONCLUSION: The LPP captures a reward-processing deficit in patients with SSD and shows potential as a biomarker for identifying patients at risk of heavy cannabis use.

Biting midges monitoring (Diptera: Ceratopogonidae: Culicoides Latreille) in the governate of Monastir (Tunisia): species composition and molecular investigations.

The results of entomological studies carried out in the governate of Monastir (Tunisia) in 2009-2010 (captures and emergences from muds) focusing on Culicoides species are presented in the present study. Identification of Culicoides at the species level is based on morphological characters, and a molecular study has been carried out based on mitochondrial DNA cytochrome C oxidase I gene (COI) and D1 and D2 domains of the 28S rDNA. The DNA sequences reported here are related to 10 species (on 25 known) of Culicoides described in Tunisia: Culicoides cataneii-gejgelensis, Culicoides circumscriptus, Culicoides imicola, Culicoides jumineri, Culicoides kingi, Culicoides langeroni, Culicoides newsteadi, Culicoides paolae, Culicoides puncticollis and Culicoides sahariensis. DNA sequencing of the COI gene and D1D2 domains discriminated all morphologically determined species. The choice of D1D2 domains considered as a conserved region is informative for Culicoides species identification. The molecular analyses of COI has grouped both C. circumscriptus, C. puncticollis within two clusters and C. newsteadi within five subclusters. However, C. newsteadi shows relatively deep intraspecific divergence using COI sequences.

The bank of standardized stimuli (BOSS): comparison between French and English norms.

Throughout the last decades, numerous picture data sets have been developed, such as the Snodgrass and Vanderwart (1980) set, and have been normalized for variables such as name and familiarity; however, due to cultural and linguistic differences, norms can vary from one country to another. The effect due specifically to culture has already been demonstrated by comparing samples from different countries where the same language is spoken. On the other hand, it is still not clear how differences between languages may affect norms. The present study explores this issue by collecting and comparing norms on names and many other features from French Canadian speakers and English Canadian speakers living in Montreal, who thus live in similar cultural environments. Norms were collected for the photos of objects from the Bank of Standardized Stimuli (BOSS) by asking participants to name the objects, to categorize them, and to rate their familiarity, visual complexity, object agreement, viewpoint agreement, and manipulability. Names and ratings from the French speakers are available in Appendix A, available in the supplemental materials. The results show that most of the norms are comparable across linguistic groups and also that the ratings given are correlated across linguistic groups. The only significant group differences were found in viewpoint agreement and visual complexity. Overall, there was good concordance between the norms collected from French and English native speakers living in the same cultural setting.

The influence of contour fragmentation on recognition memory: an event-related potential study.

The present study was carried out to examine how the event-related potentials to fragmentation predict recognition success. Stimuli were abstract meaningless figures that were either complete or fragmented to various extents but still recoverable. Stimuli were first encoded as part of a symmetry discrimination task. In a subsequent recognition phase, encoded stimuli were presented complete along with never presented stimuli and participants performed an old/new discrimination task. Fragmentation stimuli elicited more negative ERPs than complete figures over the frontal, central and parietal areas between 180 and 260 ms, and over the occipito-temporal areas between 220 and 340 ms. Only this latter effect was modulated as a function of whether stimuli were recognized or not during the recognition phase of the memory test. More specifically, the effect occurred for stimuli that were later forgotten and was absent for stimuli that were later recognized. This ERP to fragmentation, the occipito-temporal N(frag), possibly reflects the brain response to encoding difficulty, and is thus predictive of recognition performance.

Laboratory and field-based tests of deltamethrin insecticides against adult Culicoides biting midges.

Bluetongue virus (BTV) is an economically important arbovirus of ruminants transmitted by Culicoides biting midges. Vector control using residual spraying or application to livestock is recommended by many authorities to reduce BTV transmission; however, the impact of these measures in terms of both inflicting mortality on Culicoides and subsequently upon BTV transmission is unclear. This study consisted of a standardized World Health Organization laboratory assay to determine the susceptibility of European Culicoides species to deltamethrin and a field trial based upon allowing individuals of a laboratory strain of Culicoides nubeculosus Meigen to feed upon sheep treated with Butox 7.5 pour-on (a deltamethrin-based topical formulation). Susceptibility in the laboratory trial was higher in colony C. nubeculosus (24-h LC90 = 0.00106%), than in field populations of Culicoides obsoletus Meigen (24-h LC90 = 0.00203%) or Culicoides imicola Kieffer (24-h LC90 = 0.00773%). In the field, the pour-on formulation was tested with a total of 816 C. nubeculosus specimens fed upon on the thigh of treated sheep. The study revealed a maximum mortality rate of 49% at 4 d postapplication, and duration of lethal effect was predicted to be as short as 10 d, despite testing being carried out with a highly susceptible strain. The reasons for this low efficacy are discussed with reference both to the potential for lack of spread of the active ingredient on the host and feeding patterns of the major potential vector species on the sheep host. Practical implications for vector control strategies during BTV incursions are also detailed.

Efficacy of psychological interventions targeting cognitive biases in schizophrenia: A systematic review and meta-analysis.

Cognitive biases, which are tendencies to systematically process, select and remember certain information (e.g., jumping to conclusions), are exacerbated in schizophrenia and associated with delusions. Here we review and quantitatively assess psychological interventions targeting cognitive biases (e.g., metacognitive training, reasoning training, Maudsley review training programme) to evaluate their efficacy in improving cognitive biases, positive symptoms, and insight. Overall, thirty-two studies, including 15 distinct interventions and 2738 participants, were identified through a comprehensive keyword database search. Meta-analytic effect sizes were calculated and heterogeneity, publication bias, and subgroup analyses (study bias, active/passive intervention) were conducted. We observed significant small to moderate beneficial effects of cognitive interventions on cognitive biases (Hedges' g = 0.27; 95% CI = [0.13-0.41]; z = 3.77; p < .001), positive symptoms (Hedges' g = 0.30; 95% CI = [0.13-0.48]; z = 3.44, p < .005), and insight (Hedges' g = 0.35; 95% CI = [0.15-0.56]; z = 3.37,p < .005). Interestingly, studies with high risk of bias or passive control condition did not differ significantly from those with low risk or active control condition, respectively. Thus, cognitive biases are malleable via psychological interventions, which also exert, either directly or indirectly through reduced cognitive biases, beneficial effects on positive symptoms and insight.

Pharmacologic normalization of pathogenic dosage underlying genetic diseases: an overview of the literature and path forward.

Most monogenic disorders are caused by a pathologic deficit or excess of a single transcript and/or protein. Given that small molecules, including drugs, can affect levels of mRNA and protein, the pharmacologic normalization of such pathogenic dosage represents a possible therapeutic approach for such conditions. Here, we review the literature exploring pharmacologic modulation of mRNA and/or protein levels for disorders with paralogous modifier genes, for haploinsufficient disorders (insufficient gene-product), as well as toxic gain-of-function disorders (surplus or pathologic gene-product). We also discuss challenges facing the development of rare disease therapy by pharmacologic modulation of mRNA and protein. Finally, we lay out guiding principles for selection of disorders which may be amenable to this approach.

The Prevalence of Negative Symptoms Across the Stages of the Psychosis Continuum.

BACKGROUND: Patients in every stage of the psychosis continuum can present with negative symptoms. While no treatment is currently available to address these symptoms, a more refined characterization of their course over the lifetime could help in elaborating interventions. Previous reports have separately investigated the prevalence of negative symptoms within each stage of the psychosis continuum. Our aim in this review is to compare those prevalences across stages, thereby disclosing the course of negative symptoms. METHODS: We searched several databases for studies reporting prevalences of negative symptoms in each one of our predetermined stages of the psychosis continuum: clinical or ultra-high risk (UHR), first-episode of psychosis (FEP), and younger and older patients who have experienced multiple episodes of psychosis (MEP). We combined results using the definitions of negative symptoms detailed in the Brief Negative Symptom Scale, a recently developed tool. For each negative symptom, we averaged and weighted by the combined sample size the prevalences of each negative symptom at each stage. RESULTS: We selected 47 studies totaling 1872 UHR, 2947 FEP, 5039 younger MEP, and 669 older MEP patients. For each negative symptom, the prevalences showed a comparable course. Each negative symptom decreased from the UHR to FEP stages and then increased from the FEP to MEP stages. CONCLUSIONS: Certain psychological, environmental, and treatment-related factors may influence the cumulative impact of negative symptoms, presenting the possibility for early intervention to improve the long-term course.

Social Values and Determinants of Cultural Fit in Quebec: The Roles of Ancestry, Linguistic Group, and Mental Health Status.

Many quantitative cross-cultural research studies assume that cultural groups consist of anyone born and raised in the same country. Applying these criteria to the formation of study samples may produce cohorts that share a country but are heterogeneous in relevant domains of culture. For example, in Canada, Franco- and Anglo-Canadians are generally assumed to represent different linguistic groups but the same cultural group. However, speaking a different first language also can mean exposure to different media, information, and conventions, which are known to shape certain cultural domains, such as social values. Other factors may also produce cultural heterogeneity. For example, ancestral origins and recency of familial migration may influence endorsed social values after exposure to diverse cultures or norms. Mental health status or psychiatric conditions may also influence subscription of social values due to different lifestyle demands. Understanding the nuanced contributions of diverse backgrounds to cultural membership and fit (i.e., the degree to which an individual behaves like other cultural members) is useful when performing quantitative cross-cultural studies to minimize alternative explanations for statistical outcomes. This study used Cultural Consensus Analysis (CCA) to assess the cultural fit of social values for 222 Canadians, who had participated in cross-cultural neuropsychological experiments. CCA is an anthropological statistical method for evaluating cultural agreement of a sample. Participants were systematically evaluated by linguistic groups (French and English), migratory generation (1st-3rd+), and mental health status (healthy and patient). Group and individual variances were statistically interrogated. Results demonstrated that Franco- and Anglo-Canadians represent different cultural groups cohabitating in Quebec. Social values dividing Franco- and Anglo-Canadians were also identified. Second and third generation Canadians held more heterogeneous social values than Canadians, whose families had migrated earlier. Second generation Canadians with psychiatric disorders showed notably reduced cultural fit with other Canadians, which supports other literature reporting difficulties experienced by second generation migrants. However, third and later generations of Canadians with psychiatric disorders held a greater range of social values compared to healthy Canadians but still were good fits for Canadian culture. This study concluded that linguistic group and migratory generation partially determines cultural group for the social values domain while mental health status does not, contrary to theories proposed by previous literature.

Cognitive capacity similarly predicts insight into symptoms in first- and multiple-episode psychosis.

BACKGROUND: Lack of insight is a frequent characteristic of psychotic disorders, both in patients who recently experienced a first episode of psychosis (FEP) and those who experience recurrent multiple episodes (MEP). Insight is a multifaceted construct: its clinical form notably includes the unawareness of being ill, of symptoms, and of the need for treatment. Cognitive capacity is among the key determinants of insight into symptoms, but less is known about whether stage of illness (FEP vs. MEP) moderates this association. METHODS: Our aim is to evaluate the association between cognitive capacity and symptom unawareness using structural equation modeling and moderated multiple regression. A total of 193 FEP and MEP patients were assessed using the CogState battery and the Scale to Assess Unawareness of Mental Disorder. RESULTS: Analyses suggest that cognitive capacity accounts for a relatively small proportion of the total variation in symptom unawareness (6.4%). There was no evidence to suggest a moderating effect of stage of illness on this association. CONCLUSIONS: The effect of general cognitive capacity on symptom unawareness is relatively small, and this basic relation was unrelated to stage of illness. It is possible that stage of illness could moderate this association only for certain facets of insight not assessed in this study (e.g., unawareness of the need for treatment).

Indoor activity of Culicoides associated with livestock in the bluetongue virus (BTV) affected region of northern France during autumn 2006.

In August 2006, bluetongue virus (BTV) was detected in the Netherlands, Belgium, western Germany, Luxembourg and northern France for the first time. Consequently, a longitudinal entomological study was conducted in the affected region of northern France (Ardennes) throughout the autumn of 2006. Data on the spatio-temporal distribution of Culicoides (Diptera: Ceratopogonidae) associated with livestock were collected and an attempt was made to identify the vector(s) involved in BTV transmission by means of virus detection in wild-caught biting midges. Weekly sampling using standardized Onderstepoort-type blacklight traps were performed simultaneously both outdoors and indoors in one BTV-free and three BTV-affected farms between September and December 2006. Culicoides were sorted according to farm, location (outdoors vs. indoors), time point (in weeks), species and physiological stage. BTV detection was conducted by RT-PCR on monospecific pools of non-bloodfed parous female Culicoides. The principal results showed: (i) the absence of the Mediterranean vector, C. imicola, (ii) the relatively low abundance of C. dewulfi and C. pulicaris, (iii) the widespread occurrence and abundance of C. obsoletus/C. scoticus with longevity and behaviour compatible with BTV transmission, and (iv) all Culicoides pools tested for BTV were negative. In France, the very low levels of BTV-8 circulation were probably due to the limited introduction of the virus from affected neighbouring countries, and not due to the absence of local vector populations. A key finding has been the substantiation, for the first time, that Culicoides, and particularly the potential vectors C. obsoletus/C. scoticus and C. dewulfi, can be active at night inside livestock buildings and not only outside, as originally believed. The endophagic tendencies of members of the Obsoletus group are discussed in light of the prolonged period of BTV transmission during the autumn of 2006 and the risk of BTV overwintering and resurgence in the spring of 2007. Overall, there is an urgent need to improve our knowledge on the ecology of local Culicoides species before any clear, effective and reliable recommendations can be provided to the veterinary authorities in terms of prevention and control.

Comparing cognitive clusters across first- and multiple-episode of psychosis.

Cognitive impairments in psychotic disorders (PD) present heterogeneously across patients. Between 2 and 5 clusters have been identified in previous studies with first-episode (FEP) and multiple-episodes of psychosis (MEP) patients suggesting different profiles of impairment. Past findings suggest there are differences between FEP and MEP patients regarding severity and number of affected cognitive domains. Heterogeneity of cognitive deficits in PD has perhaps hindered our understanding of their course. The present study compared non-affective FEP and MEP patients to assess whether illness chronicity could influence cognitive impairment profiles. We analyzed cognitive data, collected with the Cogstate Schizophrenia Battery, of FEP and MEP patients using cluster analysis. We compared clustering methods to obtain a more robust solution. For FEP patients, data were collected at their entry to a specialized clinic; the MEP group consisted of in- and outpatients. Results suggested cognitive heterogeneity was similar in FEP and MEP samples, although in different proportions. Three clusters were identified as the most stable solution and comprised groups of patients with either 1- no cognitive impairment (over-representation of FEP), 2- generalized deficits (over-representation of MEP), or 3- intermediate impairments. These findings encourage early interventions adapted to the profile of impairment.