What Is a Group? Young Children’s Perceptions of Different Types of Groups and Group Entitativity

To date, developmental research on groups has focused mainly on in-group biases and intergroup relations. However, little is known about children’s general understanding of social groups and their perceptions of different forms of group. In this study, 5- to 6-year-old children were asked to evaluate prototypes of four key types of groups: an intimacy group (friends), a task group (people who are collaborating), a social category (people who look alike), and a loose association (people who coincidently meet at a tram stop). In line with previous work with adults, the vast majority of children perceived the intimacy group, task group, and social category, but not the loose association, to possess entitativity, that is, to be a ‘real group.’ In addition, children evaluated group member properties, social relations, and social obligations differently in each type of group, demonstrating that young children are able to distinguish between different types of in-group relations. The origins of the general group typology used by adults thus appear early in development. These findings contribute to our knowledge about children''s intuitive understanding of groups and group members'' behavior.Young children grow up in a complex social world in which they are constantly flooded with social information. Our social world is composed not only of individuals but of an array of different relationships and social groupings. One challenge for children is to decipher which of these social groupings are meaningful. People can appear to be a group from the outside, for example simply because they are in close proximity to each other, but they can be connected with each other at different levels: they can be kin or friends, be on the same sports or work team, be part of the same national or language group, or they can be associated with each other only briefly and loosely when, for instance, they take the same bus to get to the airport, or line up at a counter at the same time. Determining the type of group to which an association of people belongs is not only crucial for being able to understand individual group members’ behavior but can also be a short-cut to predicting how group members will relate to each other. For example, one can expect kin or friends to be loyal to each other, but one might not expect this about people who happen to be lining up at a counter at the same time. Another important form of predictions that can be drawn from social groupings, but which has been understudied in previous research (see also [1]), regards the grouping as a whole. For example, a friendship is supposed to be a longer-lasting, more coherent entity than a gathering in front of a counter.When it comes to the perception of social groupings, Lickel and colleagues [2] have argued that adults apply a folk typology, in which they intuitively distinguish between four qualitatively different types of groups. In support of this idea, Lickel at el. [3] investigated how adult participants sorted 40 examples of real-life groups, and how they rated each of these groups on a set of eight group characteristics such as shared goals, similarity of group members, interaction among group members, and group size. They found that participants distinguished four basic types of groups: intimacy groups (such as families and friends), task groups (such as work or sports teams), social categories (such as women or U.S. citizens), and loose associations (such as people waiting in line at a counter). Participants associated different group characteristics with each group type, for example a long duration and high levels of interaction for intimacy groups, common goals and interaction in task groups, large size and member similarity for social categories, and short duration and low levels of similarity and common goals for loose associations (for an overview, see [2]). Related research has shown that adults treat some social groupings as entities [4–6]. The extent to which a group appears to be a coherent entity and therefore possesses a quality of “groupness” has been referred to as “entitativity” [2–5, 7]. Lickel and colleagues showed that the four types of groups were perceived by adults to have different levels of entitativity, with the highest level for intimacy groups, followed by task groups, social categories, and loose associations.This group typology has received further support and validation from work in anthropology [8, 9]. Interdisciplinary work has linked these different types of groups to different relational models that are more or less prominent within each group type [10]. For example, communal sharing, a relationship in which I see “what is mine as yours” is more pronounced in intimacy groups than in other types of groups. It has been argued that children do not develop a fully-fledged concept of these different relational models before nine or ten years of age [8, 9].Despite the theoretical importance of this group typology, very little research has investigated its origins in childhood. Instead, developmental research on group cognition in young children has focused mainly on children’s in-group biases, that is, their preference for members of their own group over members of other groups. Research in this tradition has shown that children prefer members of their own group on a variety of implicit and explicit measures [11–14]. Another line of research focuses on the inferences children draw about individuals based on their group membership. For example, 4- to 6-year-old children predict what a person will do, like, or intend on the basis of that person’s gender, race, or ethnicity [15–17]. Children also use information about group membership to make inferences about social interactions: Knowing that two individuals are either from the same or from two different groups influences their prediction about whether those individuals will harm each other (around 4 years; [18]), help each other (from 6 years; [18]), or be friends with each other (from 7 years; [19]).However, this body of research leaves at least three significant gaps in our knowledge about children’s understanding of groups. First, previous research has focused primarily on just one type of group: the one Lickel and colleagues refer to as social categories, thus limiting what we can conclude about children’s understanding of group relations more generally (although see, e.g., [7, 20, 21], for work on preferential behavior towards intimacy and task group members). Second, the main focus of this previous research has been on children’s attitudes and expectations about in-group as compared with out-group members. However, as illustrated in our introductory examples, relationships among members of an in-group may differ in systematic ways depending on the type of in-group to which they belong. Finally, previous work has focused mainly on children’s perceptions of and expectations about individual group members rather than on their perceptions of and expectations about the group as a whole. It is thus important for our understanding of the development of group psychology to ask whether children distinguish different types of social groups and whether they expect relationships within and characteristics of these types of groups to differ from each other.One exception to this general trend is a study conducted by Svirydzenka and colleagues [7]. They found that 10-year-old children intuitively distinguish the same four main types of groups as adults: intimacy groups, task groups, social categories, and loose associations. They also judged the level of entitativity of different group types in similar ways as adults, but their assessments seemed to rely on group characteristics that were more perceptually salient (for example the level of interaction) than adults, who focused on more abstract features such as the importance of the group for its members [22].Inspired by this study and Lickel and colleagues’ work [3], we investigated whether the origins of this folk theory of groups could be seen even in children as young as 5 to 6 years of age. This is an important age in the development of group cognition as 5 to 6 years appears to be just at the border of explicit group understanding. It is at this age that children first show a more general preference for in-group members, even in more abstract and novel groups (in the minimal group paradigm; [21, 23]). Furthermore, it is also at this age that children first become able to predict intergroup relations in third party contexts at least for social categories (e.g., [16, 18]).Thus our objective was to investigate whether, in addition to these preferences and expectations, children of this age also have a more general understanding of groups and different types of group–in other words, an early folk typology of groups. Several prominent theoretical accounts of the origins of intergroup psychology postulate substantial development between the age group in our study and the youngest age, so far, at which a group typology has been found, 10 years [24–26]. However, given their relatively sophisticated abilities in other areas of group cognition, we predicted that already by 5 to 6 years of age, children would be able to make subtle distinctions between different types of groups and use this understanding in order to make inferences about group members’ behaviors within different group types.As a first step, we measured children’s spontaneous definition of a group. We did this to investigate children’s naïve, spontaneous ideas about groups, before presenting them with different group types. We predicted that children would be able to give some appropriate examples of groups and were especially interested in whether they would focus on one particular example or definition when thinking about groups (e.g., mention just one group type), or whether they would be able to give a more abstract definition (covering all group types, such as “a collection of people”). Second, because recent work has shown that 5-year-old children have comparable preferences for two types of group members–task group members and social category members [21]–we investigated which of these two examples (operationalized as people who work together vs. people who are similar to each other) children thought was most representative of a group. Third, we investigated whether preschool children would see an intimacy group, a task group, a social category, and a loose association as qualitatively different.It was impossible, given the young age of our participants, to adopt the exact methods of previous studies, which used complex tasks such as sorting of examples of groups and rating multiple group characteristics for each example. To simplify the procedure so that young children would understand it, we thus created a prototype for each of the four types of groups and asked children to judge these prototypes on entitativity and 12 other group characteristics. These group characteristics were generally inspired by the characteristics Lickel et al. [3] and Svirydzenka et al. [7] chose. However, in addition, we asked about several further characteristics that are important topics in recent work on the developmental origins of group psychology (e.g., [20, 27–29]) and anthropology [8, 9]. There were four main sets of group characteristics. The first three involved judgments and predictions about individual group members and group member relationships (see, e.g., [27]). The first set involved judgments about social obligations and prosocial behaviors among group members (helping, sharing, and loyalty; e.g., [18, 20, 28, 30]). The second involved the quality of group members’ social relationships (liking, familiarity, interdependence, and joint goals; [7, 31]). The third involved properties marking fundamental similarities among group members (group member similarity, shared preferences, and common knowledge; [29, 32, 33]). The fourth set, in contrast, involved traits of the group itself, concerning characteristics that apply to the group as a whole, rather than to individual members (permeability, continuance, and entitativity; [3]). We predicted generally that children’s perceptions of and expectations about groups would be contingent upon the type of group they were presented with and that they would recognize that a loose association was not a real group.     

Extinction Risk Escalates in the Tropics

The latitudinal biodiversity gradient remains one of the most widely recognized yet puzzling patterns in nature [1]. Presently, the high level of extinction of tropical species, referred to as the “tropical biodiversity crisis”, has the potential to erode this pattern. While the connection between species richness, extinction, and speciation has long intrigued biologists [2], [3], these interactions have experienced increased poignancy due to their relevancy to where we should concentrate our conservation efforts. Natural extinction is a phenomenon thought to have its own latitudinal gradient, with lower extinction rates in the tropics being reported in beetles, birds, mammals, and bivalves [4]–[7]. Processes that have buffered ecosystems from high extinction rates in the past may also buffer ecosystems against disturbance of anthropogenic origin. While potential parallels between historical and present-day extinction patterns have been acknowledged, they remain only superficially explored and plant extinction patterns have been particularly neglected. Studies on the disappearances of animal species have reached conflicting conclusions, with the rate of extinction appearing either higher [8] or lower [9] in species richness hotspots. Our global study of extinction risk in vascular plants finds disproportionately higher extinction risk in tropical countries, even when indicators of human pressure (GDP, population density, forest cover change) are taken into account. Our results are at odds with the notion that the tropics represent a museum of plant biodiversity (places of historically lowered extinction) and we discuss mechanisms that may reconcile this apparent contradiction.     

Counterproductive Effect of Saccadic Suppression during Attention Shifts

During saccadic eye movements, the processing of visual information is transiently interrupted by a mechanism known as “saccadic suppression” [1] that is thought to ensure perceptual stability [2]. If, as proposed in the premotor theory of attention [3], covert shifts of attention rely on sub-threshold recruitment of oculomotor circuits, then saccadic suppression should also occur during covert shifts. In order to test this prediction, we designed two experiments in which participants had to orient towards a cued letter, with or without saccades. We analyzed the time course of letter identification score in an “attention” task performed without saccades, using the saccadic latencies measured in the “saccade” task as a marker of covert saccadic preparation. Visual conditions were identical in all tasks. In the “attention” task, we found a drop in perceptual performance around the predicted onset time of saccades that were never performed. Importantly, this decrease in letter identification score cannot be explained by any known mechanism aligned on cue onset such as inhibition of return, masking, or microsaccades. These results show that attentional allocation triggers the same suppression mechanisms as during saccades, which is relevant during eye movements but detrimental in the context of covert orienting.     

Is the Link from Working Memory to Analogy Causal? No Analogy Improvements following Working Memory Training Gains

Analogical reasoning has been hypothesized to critically depend upon working memory through correlational data [1], but less work has tested this relationship through experimental manipulation [2]. An opportunity for examining the connection between working memory and analogical reasoning has emerged from the growing, although somewhat controversial, body of literature suggests complex working memory training can sometimes lead to working memory improvements that transfer to novel working memory tasks. This study investigated whether working memory improvements, if replicated, would increase analogical reasoning ability. We assessed participants’ performance on verbal and visual analogy tasks after a complex working memory training program incorporating verbal and spatial tasks [3], [4]. Participants’ improvements on the working memory training tasks transferred to other short-term and working memory tasks, supporting the possibility of broad effects of working memory training. However, we found no effects on analogical reasoning. We propose several possible explanations for the lack of an impact of working memory improvements on analogical reasoning.     

visPIG - A Web Tool for Producing Multi-Region,Multi-Track,Multi-Scale Plots of Genetic Data

We present VISual Plotting Interface for Genetics (visPIG; http://vispig.icr.ac.uk), a web application to produce multi-track, multi-scale, multi-region plots of genetic data. visPIG has been designed to allow users not well versed with mathematical software packages and/or programming languages such as R [1], Matlab®, Python, etc., to integrate data from multiple sources for interpretation and to easily create publication-ready figures. While web tools such as the UCSC Genome Browser [2] or the WashU Epigenome Browser [3] allow custom data uploads, such tools are primarily designed for data exploration. This is also true for the desktop-run Integrative Genomics Viewer (IGV) [4],[5]. Other locally run data visualisation software such as Circos [6] require significant computer skills of the user. The visPIG web application is a menu-based interface that allows users to upload custom data tracks and set track-specific parameters. Figures can be downloaded as PDF or PNG files. For sensitive data, the underlying R [1] code can also be downloaded and run locally. visPIG is multi-track: it can display many different data types (e.g association, functional annotation, intensity, interaction, heat map data,…). It also allows annotation of genes and other custom features in the plotted region(s). Data tracks can be plotted individually or on a single figure. visPIG is multi-region: it supports plotting multiple regions, be they kilo- or megabases apart or even on different chromosomes. Finally, visPIG is multi-scale: a sub-region of particular interest can be ''zoomed'' in. We describe the various features of visPIG and illustrate its utility with examples. visPIG is freely available through http://vispig.icr.ac.uk under a GNU General Public License (GPLv3).     

A Global Analysis of the Effectiveness of Marine Protected Areas in Preventing Coral Loss

Background

A variety of human activities have led to the recent global decline of reef-building corals [1], [2]. The ecological, social, and economic value of coral reefs has made them an international conservation priority [2], [3]. The success of Marine Protected Areas (MPAs) in restoring fish populations [4] has led to optimism that they could also benefit corals by indirectly reducing threats like overfishing, which cause coral degradation and mortality [2], [5]. However, the general efficacy of MPAs in increasing coral reef resilience has never been tested.

Methodology/Principal Findings

We compiled a global database of 8534 live coral cover surveys from 1969–2006 to compare annual changes in coral cover inside 310 MPAs to unprotected areas. We found that on average, coral cover within MPAs remained constant, while coral cover on unprotected reefs declined. Although the short-term differences between unprotected and protected reefs are modest, they could be significant over the long-term if the effects are temporally consistent. Our results also suggest that older MPAs were generally more effective in preventing coral loss. Initially, coral cover continued to decrease after MPA establishment. Several years later, however, rates of coral cover decline slowed and then stabilized so that further losses stopped.

Conclusions/Significance

These findings suggest that MPAs can be a useful tool not only for fisheries management, but also for maintaining coral cover. Furthermore, the benefits of MPAs appear to increase with the number of years since MPA establishment. Given the time needed to maximize MPA benefits, there should be increased emphasis on implementing new MPAs and strengthening the enforcement of existing MPAs.     

Archaeological Support for the Three-Stage Expansion of Modern Humans across Northeastern Eurasia and into the Americas

Background

Understanding the dynamics of the human range expansion across northeastern Eurasia during the late Pleistocene is central to establishing empirical temporal constraints on the colonization of the Americas [1]. Opinions vary widely on how and when the Americas were colonized, with advocates supporting either a pre-[2] or post-[1], [3], [4], [5], [6] last glacial maximum (LGM) colonization, via either a land bridge across Beringia [3], [4], [5], a sea-faring Pacific Rim coastal route [1], [3], a trans-Arctic route [4], or a trans-Atlantic oceanic route [5]. Here we analyze a large sample of radiocarbon dates from the northeast Eurasian Upper Paleolithic to identify the origin of this expansion, and estimate the velocity of colonization wave as it moved across northern Eurasia and into the Americas.

Methodology/Principal Findings

We use diffusion models [6], [7] to quantify these dynamics. Our results show the expansion originated in the Altai region of southern Siberia ∼46kBP , and from there expanded across northern Eurasia at an average velocity of 0.16 km per year. However, the movement of the colonizing wave was not continuous but underwent three distinct phases: 1) an initial expansion from 47-32k calBP; 2) a hiatus from ∼32-16k calBP, and 3) a second expansion after the LGM ∼16k calBP. These results provide archaeological support for the recently proposed three-stage model of the colonization of the Americas [8], [9]. Our results falsify the hypothesis of a pre-LGM terrestrial colonization of the Americas and we discuss the importance of these empirical results in the light of alternative models.

Conclusions/Significance

Our results demonstrate that the radiocarbon record of Upper Paleolithic northeastern Eurasia supports a post-LGM terrestrial colonization of the Americas falsifying the proposed pre-LGM terrestrial colonization of the Americas. We show that this expansion was not a simple process, but proceeded in three phases, consistent with genetic data, largely in response to the variable climatic conditions of late Pleistocene northeast Eurasia. Further, the constraints imposed by the spatiotemporal gradient in the empirical radiocarbon record across this entire region suggests that North America cannot have been colonized much before the existing Clovis radiocarbon record suggests.     

Community Based Case-Control Study of Rotavirus Gastroenteritis among Young Children during 2008-2010 Reveals Vast Genetic Diversity and Increased Prevalence of G9 Strains in Kolkata

Background

Group A Rotaviruses are a major etiologic agent of gastroenteritis in infants and young children (<5 years) worldwide. Although rotavirus vaccines have been successfully administered in many countries, in India the introduction of rotavirus vaccine in national immunization program was approved in 2014. Since high disease burden and large number of genetic variants have been reported from low income countries including India, monitoring of rotavirus was initiated prior to implementation of the vaccine in the region.

Methods

A total number of 3,582 stool samples were collected from an urban slum community in Kolkata, among which 1,568 samples were obtained from children of ≤5 years of age, with moderate to severe diarrhoea and 2,014 samples were collected from age-sex matched healthy neighbourhood controls. Rotavirus positive samples were typed by multiplex semi-nested PCR and nucleotide sequencing. Circulating strains were phylogenetically analyzed.

Results

Among 1,568 children with diarrhoea, 395 (25.2%), and among 2,014 asymptomatic children, 42 (2%) were rotavirus positive. G1P[8] was identified as the most common strain (32%) followed by G9P[8] (16.9%), G2P[4] (13.5%) and G9P[4] (10.75%). G12 strains with combinations of P[4], P[6] and P[8] comprised 11.9% of total positive strains. The rest (<10%) were rare and uncommon strains like G1P[4], G1P[6], G2P[8] and animal-like strains G4P[6], G6P[14] and G11P[25]. The 42 rotavirus positive samples from asymptomatic children revealed common genotypes like G1, G2 and G9.

Conclusion

This community based case-control study showed increased predominance of genotype G9 in Kolkata. It also confirmed co-circulation of a large number of genetic variants in the community. Asymptomatic rotavirus positive children though low in number can also be a source of dispersal of infection in the community. This study provides background information to the policy makers for implementation of rotavirus vaccines in this region.     

Characterization of Antibacterial and Hemolytic Activity of Synthetic Pandinin 2 Variants and Their Inhibition against Mycobacterium tuberculosis

The contention and treatment of Mycobacterium tuberculosis and other bacteria that cause infectious diseases require the use of new type of antibiotics. Pandinin 2 (Pin2) is a scorpion venom antimicrobial peptide highly hemolytic that has a central proline residue. This residue forms a structural “kink” linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked using glycine residues (P14G and P14GPG) based on the low hemolytic activities of antimicrobial peptides with structural motifs Gly and GlyProGly such as magainin 2 and ponericin G1, respectively. The two Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was less hemolytic (30%) than that of Pin2 [G] variant. In addition, based on the primary structure of Pin2 [G] and Pin2 [GPG], two short peptide variants were designed and chemically synthesized keeping attention to their physicochemical properties such as hydrophobicity and propensity to adopt alpha-helical conformations. The aim to design these two short antimicrobial peptides was to avoid the drawback cost associated to the synthesis of peptides with large sequences. The short Pin2 variants named Pin2 [14] and Pin2 [17] showed antibiotic activity against E. coli and M. tuberculosis. Besides, Pin2 [14] presented only 25% of hemolysis toward human erythrocytes at concentrations as high as 100 µM, while the peptide Pin2 [17] did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides had better activity at molar concentrations against multidrug resistance M. tuberculosis than that of the conventional antibiotics ethambutol, isoniazid and rifampicin. Therefore, Pin2 [14] and Pin2 [17] have the potential to be used as an alternative antibiotics and anti-tuberculosis agents with reduced hemolytic effects.     

A Global Regulation Inducing the Shape of Growing Folded Leaves

Shape is one of the important characteristics for the structures observed in living organisms. Whereas biologists have proposed models where the shape is controlled on a molecular level [1], physicists, following Turing [2] and d''Arcy Thomson [3], have developed theories where patterns arise spontaneously [4]. Here, we propose that volume constraints restrict the possible shapes of leaves. Focusing on palmate leaves (with lobes), the central observation is that developing leaves first grow folded inside a bud, limited by the previous and subsequent leaves. We show that the lobe perimeters end at the border of this small volume. This induces a direct relationship between the way it was folded and the final unfolded shape of the leaf. These dependencies can be approximated as simple geometrical relationships that we confirm on both folded embryonic and unfolded mature leaves. We find that independent of their position in the phylogenetic tree, these relationships work for folded species, but do not work for non-folded species. This global regulation for the leaf growth could come from a mechanical steric constraint. Such steric regulation should be more general and considered as a new simple means of global regulation.     

Pre-Saccadic Shifts of Visual Attention

The locations of visual objects to which we attend are initially mapped in a retinotopic frame of reference. Because each saccade results in a shift of images on the retina, however, the retinotopic mapping of spatial attention must be updated around the time of each eye movement. Mathôt and Theeuwes [1] recently demonstrated that a visual cue draws attention not only to the cue''s current retinotopic location, but also to a location shifted in the direction of the saccade, the “future-field”. Here we asked whether retinotopic and future-field locations have special status, or whether cue-related attention benefits exist between these locations. We measured responses to targets that appeared either at the retinotopic or future-field location of a brief, non-predictive visual cue, or at various intermediate locations between them. Attentional cues facilitated performance at both the retinotopic and future-field locations for cued relative to uncued targets, as expected. Critically, this cueing effect also occurred at intermediate locations. Our results, and those reported previously [1], imply a systematic bias of attention in the direction of the saccade, independent of any predictive remapping of attention that compensates for retinal displacements of objects across saccades [2].     

Neuroimaging Study Designs,Computational Analyses and Data Provenance Using the LONI Pipeline

Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer''s Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu.     

Phenylbutyric Acid Rescues Endoplasmic Reticulum Stress-Induced Suppression of APP Proteolysis and Prevents Apoptosis in Neuronal Cells

Background

The familial and sporadic forms of Alzheimer''s disease (AD) have an identical pathology with a severe disparity in the time of onset [1]. The pathological similarity suggests that epigenetic processes may phenocopy the Familial Alzheimer''s disease (FAD) mutations within sporadic AD. Numerous groups have demonstrated that FAD mutations in presenilin result in ‘loss of function’ of γ-secretase mediated APP cleavage [2], [3], [4], [5]. Accordingly, ER stress is prominent within the pathologically impacted brain regions in AD patients [6] and is reported to inhibit APP trafficking through the secretory pathway [7], [8]. As the maturation of APP and the cleaving secretases requires trafficking through the secretory pathway [9], [10], [11], we hypothesized that ER stress may block trafficking requisite for normal levels of APP cleavage and that the small molecular chaperone 4-phenylbutyrate (PBA) may rescue the proteolytic deficit.

Methodology/Principal Findings

The APP-Gal4VP16/Gal4-reporter screen was stably incorporated into neuroblastoma cells in order to assay γ-secretase mediated APP proteolysis under normal and pharmacologically induced ER stress conditions. Three unrelated pharmacological agents (tunicamycin, thapsigargin and brefeldin A) all repressed APP proteolysis in parallel with activation of unfolded protein response (UPR) signaling—a biochemical marker of ER stress. Co-treatment of the γ-secretase reporter cells with PBA blocked the repressive effects of tunicamycin and thapsigargin upon APP proteolysis, UPR activation, and apoptosis. In unstressed cells, PBA stimulated γ-secretase mediated cleavage of APP by 8–10 fold, in the absence of any significant effects upon amyloid production, by promoting APP trafficking through the secretory pathway and the stimulation of the non-pathogenic α/γ-cleavage.

Conclusions/Significance

ER stress represses γ-secretase mediated APP proteolysis, which replicates some of the proteolytic deficits associated with the FAD mutations. The small molecular chaperone PBA can reverse ER stress induced effects upon APP proteolysis, trafficking and cellular viability. Pharmaceutical agents, such as PBA, that stimulate α/γ-cleavage of APP by modifying intracellular trafficking should be explored as AD therapeutics.     

Mynodbcsv: Lightweight Zero-Config Database Solution for Handling Very Large CSV Files

Volumes of data used in science and industry are growing rapidly. When researchers face the challenge of analyzing them, their format is often the first obstacle. Lack of standardized ways of exploring different data layouts requires an effort each time to solve the problem from scratch. Possibility to access data in a rich, uniform manner, e.g. using Structured Query Language (SQL) would offer expressiveness and user-friendliness. Comma-separated values (CSV) are one of the most common data storage formats. Despite its simplicity, with growing file size handling it becomes non-trivial. Importing CSVs into existing databases is time-consuming and troublesome, or even impossible if its horizontal dimension reaches thousands of columns. Most databases are optimized for handling large number of rows rather than columns, therefore, performance for datasets with non-typical layouts is often unacceptable. Other challenges include schema creation, updates and repeated data imports. To address the above-mentioned problems, I present a system for accessing very large CSV-based datasets by means of SQL. It''s characterized by: “no copy” approach – data stay mostly in the CSV files; “zero configuration” – no need to specify database schema; written in C++, with boost [1], SQLite [2] and Qt [3], doesn''t require installation and has very small size; query rewriting, dynamic creation of indices for appropriate columns and static data retrieval directly from CSV files ensure efficient plan execution; effortless support for millions of columns; due to per-value typing, using mixed text/numbers data is easy; very simple network protocol provides efficient interface for MATLAB and reduces implementation time for other languages. The software is available as freeware along with educational videos on its website [4]. It doesn''t need any prerequisites to run, as all of the libraries are included in the distribution package. I test it against existing database solutions using a battery of benchmarks and discuss the results.     

DMSO Efficiently Down Regulates Pluripotency Genes in Human Embryonic Stem Cells during Definitive Endoderm Derivation and Increases the Proficiency of Hepatic Differentiation

BackgroundDefinitive endoderm (DE) is one of the three germ layers which during in vivo vertebrate development gives rise to a variety of organs including liver, lungs, thyroid and pancreas; consequently efficient in vitro initiation of stem cell differentiation to DE cells is a prerequisite for successful cellular specification to subsequent DE-derived cell types [1, 2]. In this study we present a novel approach to rapidly and efficiently down regulate pluripotency genes during initiation of differentiation to DE cells by addition of dimethyl sulfoxide (DMSO) to Activin A-based culture medium and report its effects on the downstream differentiation to hepatocyte-like cells.ResultsAddition of DMSO to the Activin A-based medium during DE specification resulted in rapid down regulation of the pluripotency genes OCT4 and NANOG, accompanied by an increase expression of the DE genes SOX17, CXCR4 and GATA4. Importantly, the expression level of ALB in DMSO-treated cells was also higher than in cells which were differentiated to the DE stage via standard Activin A treatment.     

Stimulation in the Dorsolateral Prefrontal Cortex Changes Subjective Evaluation of Percepts

Nelson and Narens have proposed a metacognition model that dissociates the objective processing of information (object-level) and the subjective evaluation of the performance (i.e., the metalevel). Neurophysiological evidence also indicates that the prefrontal cortices (PFC) are the brain areas which perform the metalevel function [1]–[3]. A corresponding neural mechanism of Nelson and Narens’s model, called dynamic filtering theory [4], [5], indicates that object-level processing is distributed in the posterior cortices and regulated by the prefrontal cortices with a filtering or gating mechanism to select appropriate signals and suppress inappropriate signals and noise. Based on this model, a hypothesis can be developed that, in the case of uncertainty or overloading of object-level processing, the prefrontal cortices will become more active in order to modulate signals and noise. This hypothesis is supported by a recent fMRI study [6] showing that the PFC (Brodmann area 9, BA9) was activated when subjects were overloaded in a bimodal attentional task, compared to a unimodal task. Here, we report a study showing that applying repetitive transmagnetic stimulation (rTMS) over the BA9 in order to interfere with its functional activity resulted in significant increas in guessed responses, compared to three other control conditions (i.e., no-TMS, sham TMS on BA9, and rTMS on Cz). The results are compatible with the dynamic filtering theory and suggest that a malfunction of the PFC would weaken the quality of meta-cognitive percepts and increase the number of guessed responses.     

Impact of HIV Comprehensive Care and Treatment on Serostatus Disclosure among Cameroonian Patients in Rural District Hospitals

This work aimed to analyze the rate of disclosure to relatives and friends over time and to identify factors affecting disclosure among seropositive adults initiating antiretroviral therapy (ART) in rural district hospitals in the context of decentralized, integrated HIV care and task-shifting to nurses in Cameroon. Stratall was a 24-month, randomized, open-label trial comparing the effectiveness of clinical monitoring alone with laboratory plus clinical monitoring on treatment outcomes. It enrolled 459 HIV-infected ART-naive adults in 9 rural district hospitals in Cameroon. Participants in both groups were sometimes visited by nurses instead of physicians. Patients with complete data both at enrolment (M0) and at least at one follow-up visit were included in the present analysis. A mixed Poisson regression was used to estimate predictors of the evolution of disclosure index over 24 months (M24).The study population included 385 patients, accounting for 1733 face-to-face interviews at follow-up visits from M0 to M24. The median [IQR] number of categories of relatives and friends to whom patients had disclosed was 2 [1]–[3] and 3 [2]–[5] at M0 and M24 (p-trend<0.001), respectively. After multiple adjustments, factors associated with disclosure to a higher number of categories of relatives and friends were as follows: having revealed one’s status to one’s main partner, time on ART, HIV diagnosis during hospitalization, knowledge on ART and positive ratio of follow-up nurse-led to physician-led visits measuring task-shifting. ART delivered in the context of decentralized, integrated HIV care including task-shifting was associated with increased HIV serological status disclosure.     

Stability-Based Comparison of Class Discovery Methods for DNA Copy Number Profiles

Motivation

Array-CGH can be used to determine DNA copy number, imbalances in which are a fundamental factor in the genesis and progression of tumors. The discovery of classes with similar patterns of array-CGH profiles therefore adds to our understanding of cancer and the treatment of patients. Various input data representations for array-CGH, dissimilarity measures between tumor samples and clustering algorithms may be used for this purpose. The choice between procedures is often difficult. An evaluation procedure is therefore required to select the best class discovery method (combination of one input data representation, one dissimilarity measure and one clustering algorithm) for array-CGH. Robustness of the resulting classes is a common requirement, but no stability-based comparison of class discovery methods for array-CGH profiles has ever been reported.

Results

We applied several class discovery methods and evaluated the stability of their solutions, with a modified version of Bertoni''s -based test [1]. Our version relaxes the assumption of independency required by original Bertoni''s -based test. We conclude that Minimal Regions of alteration (a concept introduced by [2]) for input data representation, sim [3] or agree [4] for dissimilarity measure and the use of average group distance in the clustering algorithm produce the most robust classes of array-CGH profiles.

Availability

The software is available from http://bioinfo.curie.fr/projects/cgh-clustering. It has also been partly integrated into "Visualization and analysis of array-CGH"(VAMP)[5]. The data sets used are publicly available from ACTuDB [6].