Conceptual Analysis: A Social Neuroscience Approach to Interpersonal Interaction in the Context of Disruption and Disorganization of Attachment (NAMDA)

Humans are strongly dependent upon social resources for allostasis and emotion regulation. This applies especially to early childhood because humans—as an altricial species—have a prolonged period of dependency on support and input from caregivers who typically act as sources of co-regulation. Accordingly, attachment theory proposes that the history and quality of early interactions with primary caregivers shape children's internal working models of attachment. In turn, these attachment models guide behavior, initially with the set goal of maintaining proximity to caregivers but eventually paving the way to more generalized mental representations of self and others. Mounting evidence in non-clinical populations suggests that these mental representations coincide with differential patterns of neural structure, function, and connectivity in a range of brain regions previously associated with emotional and cognitive capacities. What is currently lacking, however, is an evidence-based account of how early adverse attachment-related experiences and/or the emergence of attachment disorganization impact the developing brain. While work on early childhood adversities offers important insights, we propose that how these events become biologically embedded crucially hinges on the context of the child–caregiver attachment relationships in which the events take place. Our selective review distinguishes between direct social neuroscience research on disorganized attachment and indirect maltreatment-related research, converging on aberrant functioning in neurobiological systems subserving aversion, approach, emotion regulation, and mental state processing in the wake of severe attachment disruption. To account for heterogeneity of findings, we propose two distinct neurobiological phenotypes characterized by hyper- and hypo-arousal primarily deriving from the caregiver serving either as a threatening or as an insufficient source of co-regulation, respectively

Exclusion Expected? Cardiac Slowing Upon Peer Exclusion Links Preschool Parent Representations to School‐Age Peer Relationships

Attachment theory proposes that children’s representations of interactions with caregivers guide information‐processing about others, bridging interpersonal domains. In a longitudinal study (N = 165), preschoolers (Mage = 5.19 years) completed the MacArthur Story Stem Battery to assess parent representations. At school‐age (Mage = 8.42 years), children played a virtual ballgame with peers who eventually excluded them to track event‐related cardiac slowing, a physiological correlate of rejection, especially when unexpected. At both ages, parents and teachers reported on peer and emotional problems. During exclusion versus inclusion‐related events, cardiac slowing was associated with greater positive parent representations and fewer emerging peer problems. Cardiac slowing served as a mediator between positive parent representations and peer problems, supporting a potential psychophysiological mechanism underlying the generalization of attachment‐related representations to peer relationships

Emotional maltreatment and neglect impact neural activation upon exclusion in early and mid-adolescence: An event-related fMRI study

Child maltreatment gives rise to atypical patterns of social functioning with peers which might be particularly pronounced in early adolescence when peer influence typically peaks. Yet, few neuroimaging studies in adolescents use peer interaction paradigms to parse neural correlates of distinct maltreatment exposures. This fMRI study examines effects of abuse, neglect, and emotional maltreatment (EM) among 98 youth (n = 58 maltreated; n = 40 matched controls) using an event-related Cyberball paradigm affording assessment of both social exclusion and inclusion across early and mid-adolescence (≤13.5 years, n = 50; >13.5 years, n = 48). Younger adolescents showed increased activation to social exclusion versus inclusion in regions implicated in mentalizing (e.g., superior temporal gyrus). Individual exposure-specific analyses suggested that neglect and EM coincided with less reduction of activation to social exclusion relative to inclusion in the dorsal anterior cingulate cortex/pre-supplementary motor area (dACC/pre-SMA) among younger versus older adolescents. Integrative follow-up analyses showed that EM accounted for this dACC/pre-SMA activation pattern over and above other exposures. Moreover, age-independent results within respective exposure groups revealed that greater magnitude of neglect predicted blunted exclusion-related activity in the parahippocampal gyrus, while EM predicted increased activation to social exclusion in the precuneus/posterior cingulate cortex

Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity

There is a pressing need for host-directed therapeutics that elicit broad-spectrum antiviral activities to potentially address current and future viral pandemics. Apratoxin S4 (Apra S4) is a potent Sec61 inhibitor that prevents cotranslational translocation of secretory proteins into the endoplasmic reticulum (ER), leading to anticancer and antiangiogenic activity both in vitro and in vivo. Since Sec61 has been shown to be an essential host factor for viral proteostasis, we tested Apra S4 in cellular models of viral infection, including SARS-CoV-2, influenza A virus, and flaviviruses (Zika, West Nile, and Dengue virus). Apra S4 inhibited viral replication in a concentration-dependent manner and had high potency particularly against SARS-CoV-2 and influenza A virus, with subnanomolar activity in human cells. Characterization studies focused on SARS-CoV-2 revealed that Apra S4 impacted a post-entry stage of the viral life-cycle. Transmission electron microscopy revealed that Apra S4 blocked formation of stacked double-membrane vesicles, the sites of viral replication. Apra S4 reduced dsRNA formation and prevented viral protein production and trafficking of secretory proteins, especially the spike protein. Given the potent and broad-spectrum activity of Apra S4, further preclinical evaluation of Apra S4 and other Sec61 inhibitors as antivirals is warranted

Search for right-handed W bosons in top quark decay

We present a measurement of the fraction f+ of right-handed W bosons produced in top quark decays, based on a candidate sample of $t\bar{t}$ events in the lepton+jets decay mode. These data correspond to an integrated luminosity of 230pb^-1, collected by the DO detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. We use a constrained fit to reconstruct the kinematics of the $t\bar{t}$ and decay products, which allows for the measurement of the leptonic decay angle $\theta^*$ for each event. By comparing the $\cos\theta^*$ distribution from the data with those for the expected background and signal for various values of f+, we find f+=0.00+-0.13(stat)+-0.07(syst). This measurement is consistent with the standard model prediction of f+=3.6x10^-4.Comment: Submitted to Physical Review D Rapid Communications 7 pages, 3 figure

The Fundamental Scaling Relations of Elliptical Galaxies

(ABRIDGED) We examine the fundamental scaling relations of elliptical galaxies formed through mergers. Using hundreds of simulations to judge the impact of progenitor galaxy properties on merger remnants, we find that gas dissipation provides an important contribution to tilt in the Fundamental Plane relation. Dissipationless mergers of disks produce remnants that occupy the virial plane. As the gas content of disk galaxies is increased, the tilt of the Fundamental Plane relation increases and the slope of the Re-M_* relation steepens. For gas fractions fgas > 30%, the simulated Fundamental Plane scalings approach those observed in the K-band. In our simulations, feedback from supermassive black hole growth has only a minor influence on the stellar-mass scaling relations of spheroidal galaxies, but may play a role in maintaining the observed Fundamental Plane tilt at optical wavelengths by suppressing residual star formation in merger remnants. We estimate that \approx 40-100% of the Fundamental Plane tilt induced by structural properties owes to trends in the central total-to-stellar mass ratio M_total/M_* produced by dissipation. Lower mass systems obtain greater phase- space densities than higher mass systems, producing a galaxy mass-dependent central M_total/M_* and a corresponding tilt in the Fundamental Plane.Comment: Version accepted by ApJ, 20 pages, 18 figures, resolution reduced for siz

A search for W bb and W Higgs production in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for W b \bar{b} production in p \bar{p} collisions at sqrt{s}=1.96 TeV in events containing one electron, an imbalance in transverse momentum, and two b-tagged jets. Using 174 pb-1 of integrated luminosity accumulated by the D0 experiment at the Fermilab Tevatron collider, and the standard-model description of such events, we set a 95% C.L. upper limit on W b \bar{b}$production of 6.6 pb for b quarks with transverse momenta p_T^b > 20 GeV and b \bar{b} separation in pseudorapidity-azimuth space Delta R_bb > 0.75. Restricting the search to optimized b \bar{b} mass intervals provides upper limits on$WH$production of 9.0$-$12.2 pb, for Higgs-boson masses of 105$-$135 GeV.Comment: 7 pages, 4 figures, 1 table, submitted to Physical Review Letter

Measurement of the Ratio of B+ and B0 Meson Lifetimes

The ratio of B+ and B0 meson lifetimes was measured using data collected in 2002-2004 by the D0 experiment in Run II of the Fermilab Tevatron Collider. These mesons were reconstructed in B -> mu+ nu D*- X decays, which are dominated by B0, and B ->mu+ nu D0bar X decays, which are dominated by B+. The ratio of lifetimes is measured to be t+/t0 = 1.080 +- 0.016(stat) +- 0.014(syst).Comment: 7 pages, 2 figures, LaTeX, to be submitted to Physical Review Letter

Measurement of the Lifetime Difference in the B_s^0 System

We present a study of the decay B_s^0 -> J/psi phi We obtain the CP-odd fraction in the final state at time zero, R_perp = 0.16 +/- 0.10 (stat) +/- 0.02 (syst), the average lifetime of the (B_s, B_sbar) system, tau (B_s^0) =1.39^{+0.13}_{-0.16} (stat) ^{+0.01}_{-0.02} (syst) ps, and the relative width difference between the heavy and light mass eigenstates, Delta Gamma/Gamma = (Gamma_L - Gamma_H)/Gamma =0.24^{+0.28}_{-0.38} (stat) ^{+0.03}_{-0.04} (syst). With the additional constraint from the world average of the B_s^0$lifetime measurements using semileptonic decays, we find tau (B_s^0)= 1.39 +/- 0.06 ~ps and Delta Gamma/\Gamma = 0.25^{+0.14}_{-0.15}. For the ratio of the B_s^0 and B^0 lifetimes we obtain tau(B_s^0)/tau(B^0)} = 0.91 +/- 0.09 (stat) +/- 0.003 (syst).Comment: submitted to Phys. Rev. Lett. FERMILAB-PUB-05-324-

Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi

BACKGROUND: Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively. METHODS: Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ET(B )receptors) and endothelin-1 (an ET(A )and ET(B )receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ET(B )receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ET(A )receptors. ET(A )and ET(B )receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ET(A )and ET(B )receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies. RESULTS: After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ET(A )and ET(B )receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ET(A )and ET(B )receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ET(A )and ET(B )receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism. CONCLUSION: The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism