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This book brings the emergent interest in social class and inequality to the field of television studies. It reveals how the new visibility of class matters in serial television functions aesthetically and examines the cultural class politics articulated in these programmes. This ground-breaking volume argues that reality and quality TV's intricate politics of class entices viewers not only to grapple with previously invisible socio-economic realities but also to reconsider their class alignment. The stereotypical ways of framing class are now supplemented by those dedicated to exposing the economic and socio-psychological burdens of the (lower) middle class. The case studies in this book demonstrate how sophisticated narrative techniques coincide with equally complex ways of exposing class divisions in contemporary American life and how the examined shows disrupt the hegemonic order of class. The volume therefore also invites a rethinking of conventional models of social stratification.

Preregistration, the open science practice of specifying and registering details of a planned study prior to knowing the data, increases the transparency and reproducibility of research. Large-scale replication attempts for psychological results yielded shockingly low success rates and contributed to an increasing demand for open science practices among psychologists. However, preregistering one's studies is still not the norm in the field. Here, we conducted a study to explore possible reasons for this discrepancy. In a mixed-methods approach, we conducted an online survey assessing attitudes, motivations, and perceived obstacles with respect to preregistration. Respondents (N = 289) were psychological researchers that were recruited through their publications on Web of Science, PubMed, PSYNDEX, and PsycInfo, and preregistrations on OSF Registries. Based on the theory of planned behavior, we predicted that positive attitudes (moderated by the perceived importance of preregistration) as well as a favorable subjective norm and higher perceived behavioral control positively influence researchers' intention to preregister (directional hypothesis 1). Furthermore, we expected an influence of research experience on attitudes and perceived motivations and obstacles regarding preregistration (non-directional hypothesis 2). We analyzed these hypotheses with multiple regression models and included preregistration experience as a control variable. Researchers' attitudes, subjective norms, perceived behavioral control, and the perceived importance of preregistration significantly predicted researchers' intention to use preregistration in the future (see hypothesis 1). Research experience influenced both researchers' attitudes and their perception of motivations to preregister, but not the perception of obstacles (see hypothesis 2). Descriptive reports on researchers' attitudes, motivations and obstacles regarding preregistration are provided. Many researchers had already preregistered and had a rather positive attitude toward preregistration. Nevertheless, several obstacles were identified that may be addressed to improve and foster preregistration.

Preregistration, the open science practice of specifying and registering details of a planned study prior to knowing the data, increases the transparency and reproducibility of research. Large-scale replication attempts for psychological results yielded shockingly low success rates and contributed to an increasing demand for open science practices among psychologists. However, preregistering one's studies is still not the norm in the field. Here, we propose a study to explore possible reasons for this discrepancy. In a mixed-methods approach, an online survey will be conducted, assessing attitudes, motivations, and perceived obstacles with respect to preregistration. Participants will be psychological researchers that will be recruited by scanning research articles on Web of Science, PubMed, PSYNDEX, and PsycInfo, and preregistrations on OSF Registries (targeted sample size: N = 296). Based on the theory of planned behavior, we predict that positive attitudes (moderated by the perceived importance of preregistration) as well as a favorable subjective norm and higher perceived behavioral control positively influence researchers' intention to preregister (hypothesis 1). Furthermore, we expect an influence of research experience on attitudes and perceived motivations and obstacles regarding preregistration (hypothesis 2). We will analyze these hypotheses with multiple regression models, and will include preregistration experience as control variable.

We examined two aspects of college students' (N = 385) sense of belonging and its relations with three indicators of self-regulated learning. We also tested the mediating role of achievement goals in these relations. One aspect, sense of belonging to school, functioned as a significant predictor of self-reported metacognitive and academic time management strategies. In comparison, a second aspect, sense of belonging to peer groups, was a significant predictor of self-reported peer learning strategies. Findings from the mediation analyses indicated that sense of belonging to school was related with mastery goals, whereas sense of belonging to peer groups was related with performance goals. Further, mastery goals mediated the relations between sense of belonging to school and metacognitive and academic time management strategies.

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

Background People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes. Methods We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD). Results The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50–59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages. Conclusions We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.

This study is a first step approach towards the prediction of the proportion of grassland-based feeds (%GB) in dairy cow diets with the aid of three different groups of milk biomarkers. We aimed to evaluate and quantify the associations between biomarkers commonly suggested in the literature and %GB in individual cows as a hypothesis-generating stage for the prospective establishment of accurate %GB prediction models. Consumers and governments financially encourage sustainable, local milk production making grass-based feeding, in grassland-dominated regions, of major interest. Milk from grassland-fed cows differs from that of other feeding systems by inferential fatty acids (FA), β-carotene content and yellow color; however, these biomarkers have not been evaluated together for their association with %GB. Using approved methods of parametric regression analysis, gas chromatography (GC), mid-infrared spectra (MIR) and color spectroscopy, we aimed to develop a first step towards an easy-to-implement, cost-effective milk-based control to estimate %GB in dairy cow diets. The underlying database was generated with 24 cows each fed one of 24 different diets gradually increasing in grass silage and decreasing in corn silage. Our results indicate that GC-measured α-linolenic acid, total n-3 FA and the n-6:n-3 ratio, MIR-estimated PUFA and milk red-green color index a* are robust milk biomarkers for constructing accurate prediction models to determine %GB. Based on simplified regression analysis, diets containing 75% GB should contain ≥ 0.669 and 0.852 g α-linolenic acid and total n-3 FA per 100 g total FA, respectively, and an n-6:n-3 FA ratio of < 2.02 measured with GC; estimated with MIR, polyunsaturated FA should be ≥ 3.13 g/100 g total FA. β-carotene was not a good predictor for estimating %GB. Unexpectedly, the milk became greener with increasing %GB (negative a* values, ‒6.416 for 75% GB), suggesting the red-green color index, not yellow-blue, as a suitable biomarker.

In previous research, we demonstrated that spatial coding of proprioceptive reach targets depends on the presence of an effector movement (Mueller & Fiehler, Neuropsychologia, 2014, 2016). In these studies, participants were asked to reach in darkness with their right hand to a proprioceptive target (tactile stimulation on the finger tip) while their gaze was varied. They either moved their left, stimulated hand towards a target location or kept it stationary at this location where they received a touch on the fingertip to which they reached with their right hand. When the stimulated hand was moved, reach errors varied as a function of gaze relative to target whereas reach errors were independent of gaze when the hand was kept stationary. The present study further examines whether (a) the availability of proprioceptive online information, i.e. reaching to an online versus a remembered target, (b) the time of the effector movement, i.e. before or after target presentation, or (c) the target distance from the body influences gaze-centered coding of proprioceptive reach targets. We found gaze-dependent reach errors in the conditions which included a movement of the stimulated hand irrespective of whether proprioceptive information was available online or remembered. This suggests that an effector movement leads to gaze-centered coding for both online and remembered proprioceptive reach targets. Moreover, moving the stimulated hand before or after target presentation did not affect gaze-dependent reach errors, thus, indicating a continuous spatial update of positional signals of the stimulated hand rather than the target location per se. However, reaching to a location close to the body rather than farther away (but still within reachable space) generally decreased the influence of a gaze-centered reference frame.

Resting memory CD4+ T-cells harboring latent HIV proviruses represent a critical barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to induce HIV expression in these resting cells. Recently, it has been demonstrated that the low levels of viral gene expression induced by a candidate HDACi may be insufficient to cause the death of infected cells by viral cytopathic effects, necessitating their elimination by immune effectors, such as cytotoxic T-lymphocytes (CTL). Here, we study the impact of three HDACis in clinical development on T-cell effector functions. We report two modes of HDACi-induced functional impairment: i) the rapid suppression of cytokine production from viable T-cells induced by all three HDACis ii) the selective death of activated T-cells occurring at later time-points following transient exposures to romidepsin or, to a lesser extent, panobinostat. As a net result of these factors, HDACis impaired CTL-mediated IFN-γ production, as well as the elimination of HIV-infected or peptide-pulsed target cells, both in liquid culture and in collagen matrices. Romidepsin exerted greater inhibition of antiviral function than SAHA or panobinostat over the dose ranges tested. These data suggest that treatment with HDACis to mobilize the latent reservoir could have unintended negative impacts on the effector functions of CTL. This could influence the effectiveness of HDACi-based eradication strategies, by impairing elimination of infected cells, and is a critical consideration for trials where therapeutic interruptions are being contemplated, given the importance of CTL in containing rebound viremia.

Whereas contact sites between mitochondria and the ER have been in the focus of animal and fungal research for several years, the importance of this organellar interface and the molecular effectors are largely unknown for plants. This work gives an introduction into known evolutionary differences of molecular effectors of mitochondrial dynamics and interactions between animals, fungi, and plants. Using the model plant Physcomitrella patens, we provide microscopic evidence for the existence of mitochondria-ER interactions in plants and their correlation with mitochondrial constriction and fission. We further investigate a previously identified protein of unknown function (MELL1), and show that it modulates the amount of mitochondrial association to the ER, as well as mitochondrial shape and number.