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.

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.

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.

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.

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).

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.

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.

Sensitivity of the Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Diagnosis of Schistosoma mansoni in Low-Endemicity Settings in Côte d'Ivoire.

The sensitivity of a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for diagnosis of Schistosoma mansoni in low-endemicity settings is poorly understood. We conducted a cross-sectional survey in 14 villages in western Côte d'Ivoire and diagnosed children aged 9-12 years for schistosomiasis. Two stool samples were subjected to triplicate Kato-Katz thick smears each for diagnosis of S. mansoni, whereas a single urine sample was examined by POC-CCA for S. mansoni, filtration for Schistosoma haematobium, and reagent strip for microhematuria. According to the Kato-Katz technique, we found 45 out of 681 children positive for S. mansoni (6.6%) with a mean intensity among infected children of 72.2 eggs per gram of stool. Point-of-care circulating cathodic antigen revealed a prevalence of S. mansoni of 33.0% when trace results were considered positive and 12.5% when trace results were considered negative. Eggs of S. haematobium were found in eight participants (1.2%), whereas the prevalence of microhematuria was 13.5%. A single POC-CCA urine cassette test revealed a several-fold higher prevalence of S. mansoni than multiple Kato-Katz thick smears in this low-endemicity area. Our findings have important ramifications for choosing an appropriate diagnostic tool in low-endemic areas that might be targeted for elimination.

Schmallenberg virus in Culicoides Latreille (Diptera: Ceratopogonidae) populations in France during 2011-2012 outbreak.

Following the emergence of the Schmallenberg virus (SBV) in 2011 in Germany and its rapid spread in Europe, Culicoides (Diptera: Ceratopogonidae) collected through the French surveillance network were analysed in order to record the presence of virus genome into species diversity collected, to assess the minimum infectious rates (MIR) and the virus circulation dynamics in Culicoides populations. Two vector activity periods were selected (2011, August to October, 53 sites and 2012, June to October, 35 sites) corresponding to 704 night collections. A total of 29,285 individual midges covering at least 50 species were tested either in pools of maximum 50 females or individually (for Culicoides obsoletus/Culicoides scoticus) using real-time RT-PCR. Nine species were found SBV positive (C. obsoletus, C. scoticus, Culicoides chiopterus, Culicoides dewulfi, Culicoides imicola, Culicoides pulicaris, Culicoides newsteadi, Culicoides lupicaris and Culicoides nubeculosus) with overall MIR ranging from 0.2% to 4.2%. While the Culicoides nubeculosus laboratory strain is generally considered to have only low vector competence for viruses, interestingly, field-caught C. nubeculosus specimens were found positive twice for SBV. The first SBV-positive pool was recorded in August 2011 in north-eastern France, dating the virus circulation in France 5 months earlier than the first recorded congenital malformations and 2 months earlier than the former recorded date based on retrospective serological data. The MIR were maximum in October 2011, and in July 2012 according to dates of virus arrival in the studied areas. Moreover, our study also showed that virus circulation could be locally intense with infection rate (IR) reaching up to 16% for C. obsoletus/C. scoticus in July 2012 in one site of western France. This retrospective study demonstrates the importance of large-scale analysis to describe the spatio-temporal dynamics of virus circulation.

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.

Heightened Responses of the Parahippocampal and Retrosplenial Cortices during Contextualized Recognition of Congruent Objects.

Context sometimes helps make objects more recognizable. Previous studies using functional magnetic resonance imaging (fMRI) have examined regional neural activity when objects have strong or weak associations with their contexts. Such studies have demonstrated that activity in the parahippocampal cortex (PHC) generally corresponds with strong associations between objects and their spatial contexts while retrosplenial cortex (RSC) activity is linked with episodic memory. However these studies investigated objects viewed in associated contexts, but the direct influence of scene on the perception of visual objects has not been widely investigated. We hypothesized that the PHC and RSC may only be engaged for congruent contexts in which the object could typically be found but not for neutral contexts. While in an fMRI scanner, 15 participants rated the recognizability of 152 photographic images of objects, presented within congruent and incongruent contexts. Regions of interest were created to examine PHC and RSC activity using a hypothesis-driven approach. Exploratory analyses were also performed to identify other regional activity. In line with previous studies, PHC and RSC activity emerged when objects were viewed in congruent contexts. Activity in the RSC, inferior parietal lobe (IPL) and fusiform gyrus also emerged. These findings indicate that different brain regions are employed when objects are meaningfully contextualized.

The beneficial influence of inattention on visual interference in schizophrenia.

OBJECTIVE: Schizophrenia is associated with poor spatial attention. However, although this deficit undermines the perception of target information, it may be helpful for ignoring irrelevant inputs. The present study examined whether event-related brain potential (ERP) indices of visual spatial attention predicted the magnitude of the brain response to interference in schizophrenia. METHOD: ERPs were recorded in 16 schizophrenia patients and 20 healthy control participants who had to indicate whether the target E was global or local in compound letter stimuli. The nontarget could be either highly similar to the target (i.e., a global E composed of local Ss and vice versa) and thus produce more interference, or it could be dissimilar (i.e., a global E composed of local Hs and vice versa) and generate less interference. RESULTS: Both groups' responses were slowed by interference. Voltage amplitudes of the P1, and of ERP interference effects from 300-500 ms after stimulus onset, were significantly smaller in schizophrenia patients than in healthy participants when the target was global. In patients, larger P1 amplitudes were correlated with larger interference effects and with more severe symptoms of attentional deficits and conceptual disorganization. Schizophrenia participants thus exhibited abnormal ERPs to interference despite normal behavioral performance. CONCLUSIONS: Schizophrenia patients likely pay less attention to stimuli in general; however, the impact of this impairment on target detection is compensated by relatively greater inattention to irrelevant components of the stimuli, and this explains why they are not more influenced by interference than healthy participants at the behavioral level. (PsycINFO Database Record

Recollection rejection of new items in individuals with first-episode psychosis.

Many objects seen for the first time look familiar because they resemble known objects. To overcome this feeling of familiarity and detect novelty, memories of known objects must be recollected and compared to new objects. This experiment examines whether recollection performed when perceiving new items (i.e., recollection rejection) is abnormal in people who experienced a first episode of psychosis (FEP). Recollection of old items is impaired in this clinical population but it has not yet been demonstrated that this impairment influences the processing of new items. Eighteen FEP participants and 19 healthy controls completed an episodic memory task consisting of a study phase and a recognition phase. All the new objects looked familiar because they resembled the studied objects. Brain activity underlying false recognition and correct rejection of new objects was measured with functional resonance magnetic imaging and compared across groups. Behavioral responses to new items were not significantly different between the 2 groups. However, the between-groups analysis revealed significant differences in brain activity in the left middle frontal gyrus, the left inferior parietal lobule, the right superior parietal lobule, and the right temporal fusiform gyrus during the correct rejection of new items. This activity seems related to recollection rejection and suggests that FEP patients do not normally recollect information of past events when they process new items.

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.

Taxonomic assessment of Culicoides brunnicans, C. santonicus and C. vexans (Diptera: Ceratopogonidae) in France: Implications in systematics.

Culicoides brunnicans Edwards, 1939, Culicoides santonicus, Callot et al., 1966, and Culicoides vexans (Staeger, 1839) belong to the Vexans group of the subgenus Oecacta. These species had never been studied by molecular methods and their distribution in Western Europe overlapped. C. brunnicans and C. santonicus are two closely related species and their diagnoses are based on the wing pattern only. An integrative taxonomic approach was conducted on females of the Vexans group, Culicoides furens (the type species of the subgenus Oecacta), and Culicoides nubeculosus (as outgroup) using sequences of D1D2 rDNA domains, sequences of COI mtDNA, and wing morphometrics. Species of the Vexans group were discriminated by all traits, and were closely related in the phylogeny. Their taxonomic status and their relation to C. furens were re-evaluated.

ERP evidence for the influence of scene context on the recognition of ambiguous and unambiguous objects.

We are used to seeing objects in specific settings, and in association with other related objects. This contextual information allows for fast and efficient object recognition and influences brain-related processes. The influence of scene context has been studied using event-related potentials (ERPs) in order to further our understanding of the underlying brain mechanisms. Current ERP studies have focused on effects related to the incongruity between unambiguous objects and their scenes, rather than the specific influence of a congruent scene. The present study sought to examine ERPs associated with the beneficial influence of scene context on object recognition. This influence was examined using ambiguous objects that required a congruent scene in order to be recognized, as well as unambiguous objects, to determine whether scene processing occurs even when it is unnecessary for recognizing the object. Twenty healthy subjects were instructed to indicate whether they recognized, had a vague idea, or did not recognize target objects that appeared within congruent and neutral scenes. ERPs from 250 to 1000 ms, including the N300 and N400, were more positive at anterior sites and more negative at posterior sites, when objects appeared in congruent scenes as opposed to when they appeared in neutral scenes, with a larger effect seen for ambiguous objects. Upon further examination, the results showed that the ERPs to ambiguous objects became similar to those of unambiguous objects when they appeared in congruent contexts. These findings indicated that a congruent context exerted its influence by reducing the ambiguity of objects.

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.