The Attentional Demands of Positive Reappraisal in a Dual Task Paradigm

Title from PDF of title page, viewed October 30, 2017Thesis advisor: Diane L. FilionVitaIncludes bibliographical references (pages 52-68)Thesis (M.A.)--Department of Psychology. University of Missouri--Kansas City, 2017Emotion regulation refers to the ability to modulate experienced and expressed emotions. A specific emotion regulation strategy, cognitive reappraisal, has received extensive attention in the literature, as the strategy is widely viewed as adaptive. Cognitive reappraisal effectively alters emotional experiences through a processes of reinterpreting a stimulus, situation or event before an emotion has been fully generated. By changing the meaning of a situation before an emotion fully develops, individuals have the potential to alter the extent to which they feel certain emotions. This strategy has been associated with a wide array of beneficial health and psychological outcomes, and is also used in treating different forms of psychopathology. Despite extensive evidence documenting the effectiveness of cognitive reappraisal, researchers have recently investigated potential negative outcomes associated with this strategy. Notably, researchers have demonstrated that cognitive reappraisal requires attention, and that the attentional demands required to use this strategy can impact performance in other areas. The present study sought to expand on these findings by examining an understudied type of cognitive reappraisal: positive cognitive reappraisal. Furthermore, the present study examined how the attentional demands associated with positive cognitive reappraisal change while the strategy is being implemented as opposed to after implementation. These goals were accomplished by having participants view unpleasant and neutral images, and positively reappraise a subset of unpleasant images while performing a concurrent reaction-time (RT) task, with stimuli for the RT task presented at pseudo-random SOAs during image presentation. Results revealed greater RT during the positive reappraisal condition compared to the negative image viewing condition, and this difference changed depending on when the RT stimuli were presented. A final exploratory question examined the extent to which self-reported worry might interfere with task performance, with results revealing no impact of worry on the pattern of RT observed across conditions. The results of this study demonstrated that engaging in positive cognitive reappraisal can interfere with the ability to respond to other environmental stimuli, suggesting the strategy requires attentional resources, and that the attentional resources required to use the strategy change during the regulatory process.Introduction -- Review of the literature -- Methodology -- Results -- Discussion -- Appendi

New Wilson’s Phalarope Nesting Record from the Central Platte River Valley, Mormon Island, Hall County, Nebraska

The southeastern portion of the Wilson’s Phalarope’s (Phalaropus tricolor) breeding range encompasses parts of Nebraska (Colwell and Jehl 1994), including the Sandhills and northern Panhandle (Silcock and Jorgensen 2018). Additionally, there have been a number of breeding records from southcentral and southeastern Nebraska within the Rainwater Basin ecoregion since the mid-1990s (Mollhoff 2016, Silcock and Jorgensen 2018). However, there is very little evidence of regular breeding activity in the nearby Central Platte River Valley (CPRV), which spans from Chapman west to Overton, Nebraska, and is considered a globally important area for waterbirds (Johnsgard and Brown 2013, Silcock and Jorgensen 2018). Sutton and Arcilla (2018) documented two juvenile Wilson’s Phalaropes with two adults on 28 June 2017, confirming successful breeding in the CPRV on Mormon Island, Hall County, Nebraska. However, Sutton and Arcilla (2018) did not document an active nest and therefore lack a detailed description of the nesting habitat used by Wilson’s Phalaropes in this unique ecoregion. On 6 June 2019 we found a Wilson’s Phalarope nest while walking between avian point count stations on Mormon Island, 4.7 km northwest of Doniphan and 14.4 km southwest of Grand Island, Nebraska, on land owned and managed for the benefit of migratory birds by the Crane Trust (https://cranetrust.org/). The landscape is managed with rotational grazing and prescribed fire to simulate natural disturbance regimes (Fuhlendorf et al. 2009). Mormon Island contains the largest contiguous tract of wet meadow remaining in the CPRV (Currier and Henszey 1996, Brei and Bishop 2008). Mormon Island consists of about 1075 hectares (ha) or 2,656 acres (ac) of primarily relict and restored wet meadow and lowland tallgrass prairie habitat, and exists within a complex of 2,425 ha (5,992 ac) of land protected for conservation purposes along a 13 km (~8 mi.) stretch of the Platte River. The nest was found when an adult male Wilson’s Phalarope flushed directly off the nest from the ground at a distance of approximately 3 meters (m) from approaching observers

Landscape-Level Long-Term Biological Research and Monitoring Plan for the Crane Trust

Our obligation is to make sure we are effectively utilizing science to meet the objectives of the Platte River Whooping Crane Maintenance Trust (1981) laid out in its charter “to rehabilitate and preserve a portion of the habitat for Whooping Cranes and other migratory birds in the Big Bend reach of the Platte River between Overton and Chapman (i.e., Central Platte River Valley), Nebraska”. The original declaration is aimed at maintaining “the physical, hydrological, and biological integrity of the Big Bend area as a life-support system for the Whooping Crane and other migratory species that utilize it.” It was clear from the institution’s founding that to accomplish this goal it was necessary to study the effectiveness of land conservation and management actions in providing habitat for Whooping Cranes and other migratory bird species. Quality habitat necessarily comprises all the components that Whooping Cranes and other migratory bird life require to complete their migrations –food and shelter– including nutrient rich diet items such as invertebrates, vascular plants, herpetofauna, fish, and small mammals as well as suitable roosting and foraging locations including wide braided rivers and undisturbed wet meadows (Allen 1952; Steenhof et al. 1988; Geluso 2013; Caven et al. 2019, 2021). Article “A” of the Crane Trust’s (1981) declaration is “to establish a written habitat monitoring plan which can be used to describe change in…[habitat] within the Big Bend of the Platte River…utilized by Sandhill Cranes and Whooping Cranes….” Following initial inventories including avian (Hay and Lingle 1982), vegetation (Kolstad 1981; Nagel 1981), small mammals (Springer 1981), herpetofauna (Jones et al. 1981), insects (Ratcliffe 1981), and fish (Cochar and Jenson 1981), a variety of excellent research has continued at the Crane Trust (https://cranetrust.org/conservation-research/publications/). However, despite the clarity of the Trust’s original declaration, long-term habitat monitoring has not progressed unabated throughout the history of the Crane Trust.https://digitalcommons.unl.edu/zeabook/1130/thumbnail.jp

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but \u3e95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity

Citrullination of HP1γ chromodomain affects association with chromatin.

BACKGROUND: Stem cell differentiation involves major chromatin reorganisation, heterochromatin formation and genomic relocalisation of structural proteins, including heterochromatin protein 1 gamma (HP1γ). As the principal reader of the repressive histone marks H3K9me2/3, HP1 plays a key role in numerous processes including heterochromatin formation and maintenance. RESULTS: We find that HP1γ is citrullinated in mouse embryonic stem cells (mESCs) and this diminishes when cells differentiate, indicating that it is a dynamically regulated post-translational modification during stem cell differentiation. Peptidylarginine deiminase 4, a known regulator of pluripotency, citrullinates HP1γ in vitro. This requires R38 and R39 within the HP1γ chromodomain, and the catalytic activity is enhanced by trimethylated H3K9 (H3K9me3) peptides. Mutation of R38 and R39, designed to mimic citrullination, affects HP1γ binding to H3K9me3-containing peptides. Using live-cell single-particle tracking, we demonstrate that R38 and R39 are important for HP1γ binding to chromatin in vivo. Furthermore, their mutation reduces the residence time of HP1γ on chromatin in differentiating mESCs. CONCLUSION: Citrullination is a novel post-translational modification of the structural heterochromatin protein HP1γ in mESCs that is dynamically regulated during mESC differentiation. The citrullinated residues lie within the HP1γ chromodomain and are important for H3K9me3 binding in vitro and chromatin association in vivo.Cancer Research UK (grant reference RG17001) Wellcome Trust (Core Grant reference WT203144) Cancer Research UK (grant reference C6946/A24843). Wellcome Trust (206291/Z/17/Z) Medical Research Council (MR/P019471/1 and MR/M010082/1). Royal Society Professorship (RP150066) Medical Research Council (MR/K015850/1

Temporospatial shifts in Sandhill Crane staging in the Central Platte River Valley in response to climatic variation and habitat change

Over 80% of the Mid-Continent Sandhill Crane (Antigone canadensis) Population (MCP), estimated at over 660,000 individuals, stops in the Central Platte River Valley (CPRV) during spring migration from mid-February through mid-April. Research suggests that the MCP may be shifting its distribution spatially and temporally within the CPRV. From 2002 to 2017, we conducted weekly aerial surveys of Sandhill Cranes staging in the CPRV to examine temporal and spatial trends in their abundance and distribution. Then, we used winter temperature and drought severity measures from key wintering and early migratory stopover locations to assess the impacts of weather patterns on annual migration chronology in the CPRV. We also evaluated channel width and land cover characteristics using aerial imagery from 1938, 1998, and 2016 to assess the relationship between habitat change and the spatial distribution of the MCP in the CPRV. We used generalized linear models, cumulative link models, and Akaike’s information criterion corrected for small sample sizes (AICc) to compare temporal and spatial models. Temperatures and drought conditions at wintering and migration locations that are heavily used by Greater Sandhill Cranes (A. c. tabida) best predicted migration chronology of the MCP to the CPRV. The spatial distribution of roosting Sandhill Cranes from 2015 to 2017 was best predicted by the proportion of width reduction in the main channel since 1938 (rather than its width in 2016) and the proportion of land cover as prairie-meadow habitat within 800 m of the Platte River. Our data suggest that Sandhill Cranes advanced their migration by an average of just over 1 day per year from 2002 to 2017, and that they continued to shift eastward, concentrating at eastern reaches of the CPRV. Climate change, land use change, and habitat loss have all likely contributed to Sandhill Cranes coming earlier and staying longer in fewer reaches of the CPRV, increasing their site use intensity. These historically unprecedented densities may present a disease risk to Sandhill Cranes and other waterbirds, including Whooping Cranes (Grus americana). Our models suggest that conservation actions may be maintaining Sandhill Crane densities in areas that would otherwise be declining in use. We suggest that management actions intended to mitigate trends in the distribution of Sandhill Cranes, including wet meadow restoration, may similarly benefit prairie- and braided river–endemic species of concern. Más del 80% de la población de grullas canadienses (Antigone canadensis), de la zona central del continente (MCP por sus siglas en inglés), estimada en más de 660,000, descansa en el valle central del Río Platte (CPRV por sus siglas en inglés) durante su migración de primavera, desde mediados de febrero hasta mediados de abril. Diversos estudios indican que su distribución espacial y temporal podría estar cambiando dentro del CPRV. Desde el año 2002 hasta el 2017 realizamos sondeos aéreos semanales de grullas canadienses en el CPRV para estudiar las tendencias temporales y espaciales relacionadas a su abundancia y distribución. Usamos mediciones de temperatura durante el invierno y de la severidad de la sequía de lugares claves de invernada y de sitios de descanso durante su migración temprana para evaluar el impacto de los patrones climáticos en la cronología migratoria anual del CPRV. También analizamos la amplitud del canal y las características de la cubierta terrestre usando imágenes aéreas de 1938, 1998 y 2016 con el fin de evaluar la relación entre el cambio de hábitat y la distribución espacial de la MCP en el CPRV. Utilizamos modelos lineales generalizados, modelos de enlace acumulativo y el criterio de información de Akaike adecuados a muestras pequeñas (AICc), para comparar modelos temporales y espaciales. Las condiciones climáticas y de sequía en los sitios de invernada y migración más usados por la grulla canadiense mayor (A. c. tabida) predijeron mejor la cronología migratoria de la MCP en el CPRV. La reducción de la amplitud del canal principal desde 1938, junto con el porcentaje de cubierta terrestre como hábitat de pradera dentro de los 800 m del río Platte, fue el mejor predictor de la distribución espacial de la grulla canadiense desde el año 2015 hasta el 2017. Nuestros estudios indican que las grullas canadienses adelantaron su migración en un promedio poco más de un día por año entre el 2002 y el 2017 y que continuaron desplazándose hacia el este, concentrándose en los extremos orientales del CPRV. El cambio climático, el cambio de uso del suelo y la pérdida del hábitat probablemente contribuyeron a la migración temprana de esta especie y a su permanencia más prolongada en algunos sectores del CPRV, aumentando la intensidad del uso del sitio. Estas densidades sin precedentes podrían presentar un riesgo de enfermedad para la grulla canadiense y otras aves acuáticas, incluidas las grullas trompeteras (Grus americana). Nuestros modelos indican que las medidas actuales de conservación podrían ser la causa de preservación de la densidad poblacional de la grulla canadiense en áreas en las que, de otra forma, su presencia estaría disminuyendo. Sugerimos que las medidas de control destinadas a mitigar la tendencia de distribución de la grulla canadiense, incluyendo la restauración de los prados húmedos, pueden beneficiar de igual manera a las especies endémicas, praderas y ríos trenzados de nuestro interés

Obesity Suppresses Estrogen Receptor Beta Expression in Breast Cancer Cells via a HER2-Mediated Pathway

Obesity is associated with a worse breast cancer prognosis, while greater breast tumor estrogen receptor beta (ERβ) expression is correlated with improved therapy response and survival. The objective of this study was to determine the impact of obesity on breast cancer cell ERβ expression, which is currently unknown. We utilized an in vitro model of obesity in which breast cancer cells were exposed to patient serum pooled by body mass index category (obese (OB): ≥30 kg/m2; normal weight (N): 18.5–24.9 kg/m2). Four human mammary tumor cell lines representing the major breast cancer subtypes (SKBR3, MCF-7, ZR75, MDA-MB-231) and mammary tumor cells from MMTV-neu mice were used. ERβ expression, assessed by qPCR and western blotting, was suppressed in the two HER2-overexpressing cell lines (SKBR3, MMTV-neu) following OB versus N sera exposure, but did not vary in the other cell lines. Expression of Bcl-2 and cyclin D1, two genes negatively regulated by ERβ, was elevated in SKBR3 cells following exposure to OB versus N sera, but this difference was eliminated when the ERβ gene was silenced with siRNA. Herceptin, a HER2 antagonist, and siRNA to HER2 were used to evaluate the role of HER2 in sera-induced ERβ modulation. SKBR3 cell treatment with OB sera plus Herceptin increased ERβ expression three-fold. Similar results were obtained when HER2 expression was silenced with siRNA. OB sera also promoted greater SKBR3 cell viability and growth, but this variance was not present when ERβ was silenced or the cells were modified to overexpress ERβ. Based on this data, we conclude that obesity-associated systemic factors suppress ERβ expression in breast cancer cells via a HER2-mediated pathway, leading to greater cell viability and growth. Elucidation of the mechanism(s) mediating this effect could provide important insights into how ERβ expression is regulated as well as how obesity promotes a more aggressive disease

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)