A Closer Look at the Genomic Variation of Geographically Diverse Mycobacterium abscessus Clones That Cause Human Infection and Disease

Mycobacterium abscessus is a multidrug resistant bacterium that causes pulmonary and extrapulmonary disease. The reported prevalence of pulmonary M. abscessus infections appears to be increasing in the United States (US) and around the world. In the last five years, multiple studies have utilized whole genome sequencing to investigate the genetic epidemiology of two clinically relevant subspecies, M. abscessus subsp. abscessus (MAB) and M. abscessus subsp. massiliense (MMAS). Phylogenomic comparisons of clinical isolates revealed that substantial proportions of patients have MAB and MMAS isolates that belong to genetically similar clusters also known as ‘dominant clones’. Unlike the genetic lineages of Mycobacterium tuberculosis that tend to be geographically clustered, the MAB and MMAS clones have been found in clinical populations from the US, Europe, Australia and South America. Moreover, the clones have been associated with worse clinical outcomes and show increased pathogenicity in macrophage and mouse models. While some have suggested that they may have spread locally and then globally through ‘indirect transmission’ within cystic fibrosis (CF) clinics, isolates of these clones have also been associated with sporadic pulmonary infections in non-CF patients and unrelated hospital-acquired soft tissue infections. M. abscessus has long been thought to be acquired from the environment, but the prevalence, exposure risk and environmental reservoirs of the dominant clones are currently not known. This review summarizes the genomic studies of M. abscessus and synthesizes the current knowledge surrounding the geographically diverse dominant clones identified from patient samples. Furthermore, it discusses the limitations of core genome comparisons for studying these genetically similar isolates and explores the breadth of accessory genome variation that has been observed to date. The combination of both core and accessory genome variation among these isolates may be the key to elucidating the origin, spread and evolution of these frequent genotypes

More reliable inference for the dissimilarity index of segregation

ACL-2International audienceThe most widely used measure of segregation is the so‐called dissimilarity index. It is now well understood that this measure also reflects randomness in the allocation of individuals to units (i.e. it measures deviations from evenness, not deviations from randomness). This leads to potentially large values of the segregation index when unit sizes and/or minority proportions are small, even if there is no underlying systematic segregation. Our response to this is to produce adjustments to the index, based on an underlying statistical model. We specify the assignment problem in a very general way, with differences in conditional assignment probabilities underlying the resulting segregation. From this, we derive a likelihood ratio test for the presence of any systematic segregation, and bias adjustments to the dissimilarity index. We further develop the asymptotic distribution theory for testing hypotheses concerning the magnitude of the segregation index and show that the use of bootstrap methods can improve the size and power properties of test procedures considerably. We illustrate these methods by comparing dissimilarity indices across school districts in England to measure social segregation

Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma

Deindividuation in Anonymous Social Media: Does Anonymous Social Media Lead to an Increase in Non-Normative Behavior?

This research presents several aspects of anonymous social media postings using an anonymous social media application (i.e., Yik Yak) that is GPS-linked to college campuses. Anonymous social media been widely criticized for postings containing threats/harassment, vulgarity and suicidal intentions. However, little research has empirically examined the content of anonymous social media postings, and whether they contain a large quantity of negative social content. To best understand this phenomenon an analysis of the content of anonymous social media posts was conducted in accordance with Deindividuation Theory (Reicher, Spears, & Postmes, 1995). Deindividuation Theory predicts group behavior is congruent with group norms. Therefore, if a group norm is antisocial in nature, then so too will be group behavior. In other words, individuals relinquish their individual identity to a group identity, while they are a part of that group. Since the application used in this study is limited to a radial distance around specific college campuses, we predicted the anonymous social media users would identify as students, and behave closer to the norms expected of a student. Our results confirm that while deindividuation did occur among the college students, it did not exceed what is considered normal behavior for the social identity of a student

An Integrated Conceptual Framework Linking Attachment Insecurity to Increased Risk for Both Enacting and Experiencing Objectification

Sexual objectification (i.e., reducing a person to their appearance, body, or sex appeal and functions) is a significant risk factor for negative health outcomes. In the present investigation, we examined multiple manifestations of objectification (i.e., objectification of others, objectification of self, and objectification by others) in an interpersonal context. We merged objectification theory with attachment theory, one of the most prominent theories of close relationships, and propose that sexual objectification can shed light on attachment processes (and vice versa). To bolster this conceptual overlap, we tested this novel, integrated framework across two independent samples of women and men including (a) a sample of 813 undergraduate students—both partnered and single—who completed self-report questionnaires of attachment security and multiple forms of objectification and (b) a sample of 159 committed couples navigating pregnancy who were observed during naturalistic interactions to assess attachment security and completed self-report questionnaires of attachment security and objectification (including partner objectification). Results from both studies demonstrate the utility of our proposed conceptual framework linking attachment insecurity to increased risk for both enacting and experiencing objectification. The most compelling evidence emerged for (a) a link between attachment anxiety and self-objectification with moderate effect sizes across both samples, and (b) an association between a less secure base within the couple relationship during pregnancy and feeling more objectified by one’s partner as well as less humanized (i.e., feeling that your partner values you more for your physical attributes and less for your non-physical attributes)

Electronic Conductance and Thermopower of Cross-Conjugated and Skipped-Conjugated Molecules in Single-Molecule Junctions

We report a combined experimental and theoretical study of a series of thiomethyl (SMe) anchored cross-conjugated molecules featuring an acyclic central bridging ketone and their analogous skipped-conjugated alcohol derivatives. Studies of these molecules in a gold|single-molecule|gold junction using scanning tunneling microscopy-break junction techniques reveal a similar conductance (G) value for both the cross-conjugated molecules and their skipped-conjugated partners. Theoretical studies based on density functional theory of the molecules in their optimum geometries in the junction reveal the reason for this similarity in conductance, as the predicted conductance for the alcohol series of compounds varies more with the tilt angle. Thermopower measurements reveal a higher Seebeck coefficient (S) for the cross-conjugated ketone molecules relative to the alcohol derivatives, with a particularly high S for the biphenyl derivative 3a (−15.6 μV/K), an increase of threefold compared to its alcohol analog. The predicted behavior of the quantum interference (QI) in this series of cross-conjugated molecules is found to be constructive, though the appearance of a destructive QI feature for 3a is due to the degeneracy of the HOMO orbital and may explain the enhancement of the value of S for this molecule

Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration

Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loosely connected neural crest cells (NCCs) lead us to hypothesize that NCC remodeling of an initially punctate ECM creates a scaffold for trailing cells, enabling them to form robust and coherent stream patterns. We evaluate this idea in a theoretical setting by developing an agent-based model that incorporates reciprocal interactions between NCCs and their ECM. ECM remodeling, haptotaxis, contact guidance, and cell-cell repulsion are sufficient for cells to establish streams in silico, however additional mechanisms, such as chemotaxis, are required to consistently guide cells along the correct target corridor. Further investigations of the model imply that contact guidance and differential cell-cell repulsion between leader and follower cells are key contributors to robust collective cell migration by preventing stream breakage. Global sensitivity analysis and simulated underexpression/overexpression experiments suggest that long-distance migration without jamming is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance.Comment: 46 pages, 7 figures (of which 2 are supplementary