Impulsivity, Venturesomeness, and Pride: Potential Moderators of the Relationship Between Childhood Trauma, Substance Use, and Physical Aggression

Impulsivity, venturesomeness, and pride variables were examined as potential moderators of the associations between childhood trauma and physical aggression, alcohol use and physical aggression, and drug use and physical aggression. Participants (n = 457) were college students recruited from a university in the Southeast. It was hypothesized that childhood trauma, alcohol use, and drug use would be associated with increased scores of physical aggression. In addition, it was hypothesized that impulsivity, venturesomeness, authentic pride, and hubristic pride would moderate these relationships. Linear, multivariate hierarchical regression analyses were used to examine these variables as potential moderators. Hypotheses concerning hubristic pride as a moderator of the relationship between alcohol use and physical aggression as well as the relationship between drug use and physical aggression were supported. In addition, the hypothesis concerning authentic pride as a moderator of the relationship between alcohol use and physical aggression was supported albeit in the opposite direction than predicted. Hypotheses concerning the moderating roles of impulsivity and venturesomeness were not supported. Findings support the idea that the deleterious psychological effects of substance use can be compounded by personality factors such as authentic and hubristic pride. The discussion encompasses why interventions should target attributions and cognitions and why simply encouraging someone to have a more “healthy pride” is likely to be ineffective at reducing physical aggression in the context of drug use and alcohol use

Functional Impairment, Illness Burden, and Depressive Symptoms in Older Adults: Does Type of Social Relationship Matter?

Objective: The nature of interpersonal relationships, whether supportive or critical, may affect the association between health status and mental health outcomes. We examined the potential moderating effects of social support, as a buffer, and family criticism, as an exacerbating factor, on the association between illness burden, functional impairment and depressive symptoms. Methods: Our sample of 735 older adults, 65 years and older, was recruited from internal and family medicine primary care offices. Trained interviewers administered the Hamilton Rating Scale for Depression, Duke Social Support Inventory, and Family Emotional Involvement and Criticism Scale. Physician-rated assessments of health, including the Karnofsky Performance Status Scale and Cumulative Illness Rating Scale, were also completed. Results: Linear multivariable hierarchical regression results indicate that social interaction was a significant buffer, weakening the association between illness burden and depressive symptoms, whereas perceived social support buffered the relationship between functional impairment and depressive symptoms. Family criticism and instrumental social support were not significant moderators. Conclusions: Type of medical dysfunction, whether illness or impairment, may require different therapeutic and supportive approaches. Enhancement of perceived social support, for those who are impaired, and encouragement of social interactions, for those who are ill, may be important intervention targets for treatment of depressive symptoms in older adult primary care patients

Coupled Contagion Dynamics of Fear and Disease: Mathematical and Computational Explorations

Background: In classical mathematical epidemiology, individuals do not adapt their contact behavior during epidemics. They do not endogenously engage, for example, in social distancing based on fear. Yet, adaptive behavior is welldocumented in true epidemics. We explore the effect of including such behavior in models of epidemic dynamics. Methodology/Principal Findings: Using both nonlinear dynamical systems and agent-based computation, we model two interacting contagion processes: one of disease and one of fear of the disease. Individuals can ‘‘contract’ ’ fear through contact with individuals who are infected with the disease (the sick), infected with fear only (the scared), and infected with both fear and disease (the sick and scared). Scared individuals–whether sick or not–may remove themselves from circulation with some probability, which affects the contact dynamic, and thus the disease epidemic proper. If we allow individuals to recover from fear and return to circulation, the coupled dynamics become quite rich, and can include multiple waves of infection. We also study flight as a behavioral response. Conclusions/Significance: In a spatially extended setting, even relatively small levels of fear-inspired flight can have a dramatic impact on spatio-temporal epidemic dynamics. Self-isolation and spatial flight are only two of many possible actions that fear-infected individuals may take. Our main point is that behavioral adaptation of some sort must b

Superhelical Duplex Destabilization and the Recombination Position Effect

The susceptibility to recombination of a plasmid inserted into a chromosome varies with its genomic position. This recombination position effect is known to correlate with the average G+C content of the flanking sequences. Here we propose that this effect could be mediated by changes in the susceptibility to superhelical duplex destabilization that would occur. We use standard nonparametric statistical tests, regression analysis and principal component analysis to identify statistically significant differences in the destabilization profiles calculated for the plasmid in different contexts, and correlate the results with their measured recombination rates. We show that the flanking sequences significantly affect the free energy of denaturation at specific sites interior to the plasmid. These changes correlate well with experimentally measured variations of the recombination rates within the plasmid. This correlation of recombination rate with superhelical destabilization properties of the inserted plasmid DNA is stronger than that with average G+C content of the flanking sequences. This model suggests a possible mechanism by which flanking sequence base composition, which is not itself a context-dependent attribute, can affect recombination rates at positions within the plasmid

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Functional impairment, illness burden, and depressive symptoms in older adults: does type of social relationship matter

Objective: The nature of interpersonal relationships, whether supportive or critical, may affect the association between health status and mental health outcomes. We examined the potential moderating effects of social support, as a buffer, and family criticism, as an exacerbating factor, on the association between illness burden, functional impairment and depressive symptoms. Methods: Our sample of 735 older adults, 65 years and older, was recruited from internal and family medicine primary care offices. Trained interviewers administered the Hamilton Rating Scale for Depression, Duke Social Support Inventory, and Family Emotional Involvement and Criticism Scale. Physician-rated assessments of health, including the Karnofsky Performance Status Scale and Cumulative Illness Rating Scale, were also completed. Results: Linear multivariable hierarchical regression results indicate that social interaction was a significant buffer, weakening the association between illness burden and depressive symptoms, whereas perceived social support buffered the relationship between functional impairment and depressive symptoms. Family criticism and instrumental social support were not significant moderators. Conclusions: Type of medical dysfunction, whether illness or impairment, may require different therapeutic and supportive approaches. Enhancement of perceived social support, for those who are impaired, and encouragement of social interactions, for those who are ill, may be important intervention targets for treatment of depressive symptoms in older adult primary care patients