A Critical Review of the “Undoing Hypothesis”: Do Positive Emotions Undo the Effects of Stress?

Research in affective science has shown that trait positive affect reduces the risk of developing disease and is protective against the progression of certain diseases. Research also suggests that trait positive affect predisposes individuals to more frequent experiences of positive emotional states. The undoing effect has been proposed as a potential mechanism explaining how positive emotions influence health outcomes. According to this hypothesis, the experience of state positive emotions or positive affect contributes to faster recovery from the body’s physiological response to stress. This paper critically reviews literature concerning the undoing hypothesis. Several common methodological weaknesses were identified, including conceptual and design issues. Based on the reviewed studies two separate conclusions were drawn. First, there was insufficient evidence to conclude that the occurrence of positive emotional states speeds physiological recovery. Second, there was insufficient evidence to evaluate the undoing hypothesis as a potential mechanism through which state positive emotions affect health. Future research should focus on identifying the key parameters responsible for demonstrating the undoing effect when it is observed in order to understand how the experience of positive emotions may exert positive effects on health outcomes.     

Modelling multilocus selection in an individual‐based,spatially‐explicit landscape genetics framework

We implemented multilocus selection in a spatially‐explicit, individual‐based framework that enables multivariate environmental gradients to drive selection in many loci as a new module for the landscape genetics programs, CDPOP and CDMetaPOP. Our module simulates multilocus selection using a linear additive model, providing a flexible platform to evaluate a wide range of genotype‐environment associations. Importantly, the module allows simulation of selection in any number of loci under the influence of any number of environmental variables. We validated the module with individual‐based selection simulations under Wright‐Fisher assumptions. We then evaluated results for simulations under a simple landscape selection model. Next, we simulated individual‐based multilocus selection across a complex selection landscape with three loci linked to three different environmental variables. Finally, we demonstrated how the program can be used to simulate multilocus selection under varying selection strengths across different levels of gene flow in a landscape genetics framework. This new module provides a valuable addition to the study of landscape genetics, allowing for explicit evaluation of the contributions and interactions between gene flow and selection‐driven processes across complex, multivariate environmental and landscape conditions.     

Detection of a Novel Bovine Lymphotropic Herpesvirus

Degenerate PCR primers which amplify a conserved region of the DNA polymerase genes of the herpesvirus family were used to provide sequence evidence for a new bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear cells (PBMC). The sequence of the resultant amplicon was found to be distinct from those of known herpesvirus isolates. Alignment of amino acid sequences demonstrated 70% identity with ovine herpesvirus 2, 69% with alcelaphine herpesvirus 1, 65% with bovine herpesvirus 4, and 42% with bovine herpesvirus 1. Phylogenetic analysis placed this putative virus within the tumorigenic Gammaherpesvirinae subfamily, and it is tentatively identified as bovine lymphotropic herpesvirus. This novel agent was expressed in vitro from infected PBMC, and cell-free supernatants were used to transfer infection to a bovine B-cell line, BL3. Analysis, with specific PCR primers, of DNA from bovine PBMC and lymphoma cells identified infection in blood of 91% of adult animals (n = 101), 63% of lymphomas (n = 32), and 38% of juveniles (n = 13). Of the adults, herpesvirus infection was present in 94% of animals that were seropositive for bovine leukemia virus (BLV) (n = 63) and in 87% of BLV-seronegative animals (n = 38). Of the seropositive group, 17 animals exhibited persistent lymphocytosis, and 100% of these were herpesvirus positive by PCR. A role for bovine lymphotropic herpesvirus as a cofactor in BLV pathogenesis is considered.     

Restricted heterogeneity of antibody to gp120 and p24 in AIDS

Neurologic complications and cerebrospinal fluid (CSF) abnormalities are common in AIDS. We found that a substantial number of AIDS patients with neurologic involvement had oligoclonal IgG bands in CSF and sera by IEF. Using an IEF-Ag overlay technique, anti-gp120 antibody activity was demonstrated more frequently than anti-p24 antibody activity. These antibody activities exhibited restricted heterogeneity of their IEF pattern; this restriction may contribute to the relatively low titers of neutralizing antibody found in AIDS sera. None of the CSF and serum oligoclonal bands showed anti-HIV antibody activity, suggesting that they are directed against opportunistic agents or result from immunodysregulation.     

RGK regulation of voltage-gated calcium channels

Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.     

Improving probabilistic infectious disease forecasting through coherence

With an estimated $10.4 billion in medical costs and 31.4 million outpatient visits each year, influenza poses a serious burden of disease in the United States. To provide insights and advance warning into the spread of influenza, the U.S. Centers for Disease Control and Prevention (CDC) runs a challenge for forecasting weighted influenza-like illness (wILI) at the national and regional level. Many models produce independent forecasts for each geographical unit, ignoring the constraint that the national wILI is a weighted sum of regional wILI, where the weights correspond to the population size of the region. We propose a novel algorithm that transforms a set of independent forecast distributions to obey this constraint, which we refer to as probabilistically coherent. Enforcing probabilistic coherence led to an increase in forecast skill for 79% of the models we tested over multiple flu seasons, highlighting the importance of respecting the forecasting system’s geographical hierarchy.     

Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis

Two component systems (TCSs) are a primary mechanism of signal sensing and response in bacteria. Systematic characterization of an entire TCS could provide a mechanistic understanding of these important signal transduction systems. Here, genetic selections were employed to dissect the molecular basis of signal transduction by the HitRS system that detects cell envelope stress in the pathogen Bacillus anthracis. Numerous point mutations were isolated within HitRS, 17 of which were in a 50-residue HAMP domain. Mutational analysis revealed the importance of hydrophobic interactions within the HAMP domain and highlighted its essentiality in TCS signaling. In addition, these data defined residues critical for activities intrinsic to HitRS, uncovered specific interactions among individual domains and between the two signaling proteins, and revealed that phosphotransfer is the rate-limiting step for signal transduction. Furthermore, this study establishes the use of unbiased genetic selections to study TCS signaling and provides a comprehensive mechanistic understanding of an entire TCS.