Conventional wisdom holds that partisanship and political ideology, writ large, are some of the most powerful explanations of attitudes towards climate change and environmental politics. While ...compelling, most studies focus on a narrow definition of political ideology in the US. This study adds to the literature by assessing the relationship between populism, climate skepticism, and support for environmental protection. Populism offers an orthogonal dimension to partisanship and left-right self-placement, which broadens the scope of the concept. Assessing the UK facilitates understanding the role of political ideology beyond the strong party sorting apparent in the US. Data from the 2015 British Election Study offer strong support for the proposition that populism holds a consequential role in climate and environmental politics.
Ceroid lipofuscinosis neuronal (CLN) genes encode 13 proteins that localize throughout the endomembrane system to regulate a variety of cellular processes. In humans, mutations in CLN genes cause a ...devastating form of neurodegeneration called neuronal ceroid lipofuscinosis (NCL), commonly known as Batten disease. Each CLN gene is associated with a specific subtype of the disease that differ from each other in severity and age of onset. The NCLs affect all ages and ethnicities worldwide but primarily affect children. The pathology underlying the NCLs is poorly understood, which has prevented the development of a cure or effective therapy for most subtypes of the disease. A growing body of literature supports the networking of CLN genes and proteins within cells, which aligns with the broadly similar cellular and clinical manifestations among the different subtypes of NCL. Here, all relevant literature is reviewed to provide a comprehensive overview of our current understanding of how CLN genes and proteins are networked in mammalian cells with an aim toward revealing new molecular targets for therapy development. Intriguingly, CLN gene and protein networking extends beyond the NCLs as recent work has linked several CLN genes and proteins to other forms of neurodegeneration such as Alzheimer's disease and Parkinson's disease. Thus, a deeper understanding of the pathways and cellular processes impacted by mutations in CLN genes will not only strengthen our knowledge of the pathological mechanisms underlying the NCLs but may also provide new insight into related forms of neurodegeneration.
Despite the burgeoning literature, evidence on how right-wing populists frame and act on energy and climate issues is limited and even more scarce for other types of populist parties. We address this ...gap by exploring the policy discourses, positions and actions of six European populist parties from Austria, Czechia, Greece, Italy, Poland and Spain belonging to different types of populism. We argue that there is substantial and largely neglected variation among different populist parties in their approach to and effects on EU energy and climate policy (ECP). We find support for the notion that right-wing and right-leaning valence populist parties are at odds with ambitious EU ECP. On the contrary, the analysed left-wing and left-leaning valence populists rely on populist discourses to demand more ambitious ECP measures. Furthermore, our analysis suggests that participation in government decreases the role of populism in parties' ECP discourse and dilutes parties' positions and actions.
The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are a group of neurological diseases that affect all ages and ethnicities worldwide. There are 13 different subtypes ...of NCL, each caused by a mutation in a distinct gene. The NCLs are characterized by the accumulation of undigestible lipids and proteins in various cell types. This leads to progressive neurodegeneration and clinical symptoms including vision loss, progressive motor and cognitive decline, seizures, and premature death. These diseases have commonly been characterized by lysosomal defects leading to the accumulation of undigestible material but further research on the NCLs suggests that altered protein secretion may also play an important role. This has been strengthened by recent work in biomedical model organisms, including Dictyostelium discoideum, mice, and sheep. Research in D. discoideum has reported the extracellular localization of some NCL-related proteins and the effects of NCL-related gene loss on protein secretion during unicellular growth and multicellular development. Aberrant protein secretion has also been observed in mammalian models of NCL, which has allowed examination of patient-derived cerebrospinal fluid and urine for potential diagnostic and prognostic biomarkers. Accumulated evidence links seven of the 13 known NCL-related genes to protein secretion, suggesting that altered secretion is a common hallmark of multiple NCL subtypes. This Review highlights the impact of altered protein secretion in the NCLs, identifies potential biomarkers of interest and suggests that future work in this area can provide new therapeutic insight.
The neuronal ceroid lipofuscinoses (NCLs), commonly known as Batten disease, belong to a family of neurological disorders that cause blindness, seizures, loss of motor function and cognitive ability, ...and premature death. There are 13 different subtypes of NCL that are associated with mutations in 13 genetically distinct genes (CLN1-CLN8, CLN10-CLN14). Similar clinical and pathological profiles of the different NCL subtypes suggest that common disease mechanisms may be involved. As a result, there have been many efforts to determine how NCL proteins are connected at the cellular level. A main driving force for NCL research has been the utilization of mammalian and non-mammalian cellular models to study the mechanisms underlying the disease. One non-mammalian model that has provided significant insight into NCL protein function is the social amoeba Dictyostelium discoideum. Accumulated data from Dictyostelium and mammalian cells show that NCL proteins display similar localizations, have common binding partners, and regulate the expression and activities of one another. In addition, genetic models of NCL display similar phenotypes. This review integrates findings from Dictyostelium and mammalian models of NCL to highlight our understanding of the molecular networking of NCL proteins. The goal here is to help set the stage for future work to reveal the cellular mechanisms underlying the NCLs.
Neuronal ceroid lipofuscinosis (NCL), also referred to as Batten disease, is the most common form of childhood neurodegeneration. Mutations in CLN3 cause the most prevalent subtype of the disease, ...which manifests during early childhood and is currently untreatable. The precise function of the CLN3 protein is still not known, which has inhibited the development of targeted therapies. In the social amoeba Dictyostelium discoideum, loss of the CLN3 homolog, Cln3, reduces adhesion during early development, which delays streaming and aggregation. The results of the present study indicate that this phenotype may be at least partly due to aberrant protein secretion in cln3− cells. It is well-established that Cln3 localizes primarily to the contractile vacuole (CV) system in Dictyostelium, and to a lesser extent, compartments of the endocytic pathway. Intriguingly, the CV system has been linked to the secretion of proteins that do not contain a signal peptide for secretion (i.e., unconventional protein secretion). Proteins that do contain a signal peptide are secreted via a conventional mechanism involving the endoplasmic reticulum, transport through the Golgi, and secretion via vesicle release. In this study, Cln3 was observed to co-localize with the Golgi marker wheat germ agglutinin suggesting that Cln3 participates in both secretion mechanisms. Chimeras of wild-type (WT) and cln3− cells displayed delayed streaming and aggregation, and interestingly, cln3− cells starved in conditioned media (CM) harvested from starving WT cells showed near normal timing of streaming and aggregation suggesting aberrant protein secretion in Cln3-deficient cells. Based on these observations, LC-MS/MS was used to reveal the protein content of CM from starved cells (mass spectrometry data are available via ProteomeXchange with identifier PXD004897). A total of 450 proteins were detected in WT and cln3− CM, of which 3 were absent in cln3− CM. Moreover, 12 proteins that were present in cln3− CM were absent in WT CM. Label-free quantification identified 42 proteins that were present in significantly higher amounts in cln3− CM compared to WT, and 3 proteins that were present in significantly reduced amounts. A GO term enrichment analysis showed that a majority of the affected proteins are linked to endocytosis, vesicle-mediated transport, proteolysis, and metabolism. In total, the results of this study indicate that Cln3 functions in both conventional and unconventional protein secretion and that loss of Cln3 results in deregulated secretion during early development. Importantly, this is the first evidence in any system linking CLN3 function to protein secretion.
Ceroid lipofuscinosis neuronal 5 (CLN5) is a member of a family of proteins that are linked to neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, known commonly as Batten ...disease, affects all ages and ethnicities and is currently incurable. The precise function of CLN5, like many of the NCL proteins, remains to be elucidated. In this study, we report the localization, molecular function, and interactome of Cln5, the CLN5 homolog in the social amoeba Dictyostelium discoideum. Residues that are glycosylated in human CLN5 are conserved in the Dictyostelium homolog as are residues that are mutated in patients with CLN5 disease. Dictyostelium Cln5 contains a putative signal peptide for secretion and we show that the protein is secreted during growth and starvation. We also reveal that both Dictyostelium Cln5 and human CLN5 are glycoside hydrolases, providing the first evidence in any system linking a molecular function to CLN5. Finally, immunoprecipitation coupled with mass spectrometry identified 61 proteins that interact with Cln5 in Dictyostelium. Of the 61 proteins, 67% localize to the extracellular space, 28% to intracellular vesicles, and 20% to lysosomes. A GO term enrichment analysis revealed that a majority of the interacting proteins are involved in metabolism, catabolism, proteolysis, and hydrolysis, and include other NCL-like proteins (e.g., Tpp1/Cln2, cathepsin D/Cln10, cathepsin F/Cln13) as well as proteins linked to Cln3 function in Dictyostelium (e.g., AprA, CfaD, CadA). In total, this work reveals a CLN5 homolog in Dictyostelium and further establishes this organism as a complementary model system for studying the functions of proteins linked to NCL in humans.
•The social amoeba Dictyostelium discoideum contains a homolog of human CLN5 (Cln5).•Dictyostelium Cln5 is secreted.•Dictyostelium Cln5 and human CLN5 are glycoside hydrolases.•Dictyostelium Cln5 interacts with 61 proteins during early stage development.•Dictyostelium Cln5 interacts with other NCL protein homologs.
In industrialised countries, emissions from fossil-fuelled vehicles show little sign of abatement, with citizens' opposition to policy interventions arguably the key reason. To better understand the ...sources of public opinion towards particular types of policy instruments designed to reduce vehicle emissions, we focus on the perceived consequences of such instruments, notably the extent to which they are regarded as effective, fair, and unintrusive. Switzerland is the empirical focus because it lags behind neighbouring European countries. We assess public support for seven policy instruments, identified by existing literature and expert interviews. A survey-embedded experiment with a representative sample of 2,034 citizens provides support for the argument that policy instruments perceived as effective, fair, and unintrusive achieve higher levels of public support. These results may help policymakers design interventions that strike a balance between political feasibility and problem-solving effectiveness.
In this paper, we seek to identify robust predictors of individuals’ attitudes towards climate change and environmental degradation. While much of the extant literature has been devoted to the ...individual explanatory potential of individuals’ characteristics, we focus on the extent to which these characteristics provide robust predictions of climate and environmental attitudes. Thereby, we adjudicate the relative predictive power of psychological and sociodemographic characteristics, as well as the predictive power of combinations of these attributes. To do so, we use a popular machine learning technique, Random Forests, on three surveys fielded in China, Switzerland, and the USA, using a variety of outcome variables. We find that a psychological construct, the consideration of future consequences (CFC) scale, performs well in predicting attitudes, across all contexts and better than traditional explanations of climate attitudes, such as income and education. Given recent advances suggesting potential psychological barriers of behavioural change Public (Weaver, Adm Rev 75:806–816,
2015
) and the use of psychological constructs to target persuasive messages (Abrahamse et al., J Environ Psychol 265–276,
2007
; Hirsh et al., Psychol Sci 23:578–581,
2012
), identifying important predictors, such as the CFC may allow to better understand public’s appetite for climate and environmental policies and increase demand for these policies, in an area where existing efforts have shown to be lacking (Bernauer and McGrath, Nat Clim Chang 6:680–683,
2016
; Chapman et al., Nat Clim Chang 7:850–852,
2017
).
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