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This article elaborates relative deprivation theory to a societal level to argue that political unrest is rooted in the polarization of citizens' grievance judgments, rather than the mean level of societal grievance. Using data from twelve cross-national survey projects, it examines the relationship between citizen polarization and political protest in eighty-four democracies and semi-democracies from 1977 to 2010. The study finds that countries with more polarized citizens are more likely to experience nonviolent protest. Protests are most likely in countries where average citizen grievances are low but citizens are polarized, which is consistent with the elaborated theoretical expectations of relative deprivation theory.

Context Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking predominantly noncoding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss of function (LoF) would be of most therapeutic benefit. Objective This work aimed to identify genes/proteins involved in determining fat distribution. Methods We combined the power of genome-wide analysis of array-based rare, nonsynonymous variants in 450 562 individuals in the UK Biobank with exome-sequence-based rare LoF gene burden testing in 184 246 individuals. Results The data indicate that the LoF of 4 genes (PLIN1 [LoF variants, P = 5.86 × 10–7], INSR [LoF variants, P = 6.21 × 10–7], ACVR1C [LoF + moderate impact variants, P = 1.68 × 10–7; moderate impact variants, P = 4.57 × 10–7], and PDE3B [LoF variants, P = 1.41 × 10–6]) is associated with a beneficial effect on body mass index–adjusted waist-to-hip ratio and increased gluteofemoral fat mass, whereas LoF of PLIN4 (LoF variants, P = 5.86 × 10–7 adversely affects these parameters. Phenotypic follow-up suggests that LoF of PLIN1, PDE3B, and ACVR1C favorably affects metabolic phenotypes (eg, triglycerides [TGs] and high-density lipoprotein [HDL] cholesterol concentrations) and reduces the risk of cardiovascular disease, whereas PLIN4 LoF has adverse health consequences. INSR LoF is associated with lower TG and HDL levels but may increase the risk of type 2 diabetes. Conclusion This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counterintuitive insight into the potential consequences of targeting these molecules therapeutically.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2073-4409/10/5/1016 Este artículo pertenece al número especial "Highlights in Autophagy: From Basic Mechanisms to Human Disorder Treatments". An imbalance in the storage and breakdown of hepatic lipid droplet (LD) triglyceride (TAG) leads to hepatic steatosis, a defining feature of non-alcoholic fatty liver disease (NAFLD). The two primary cellular pathways regulating hepatic TAG catabolism are lipolysis, initiated by adipose triglyceride lipase (ATGL), and lipophagy. Each of these processes requires access to the LD surface to initiate LD TAG catabolism. Ablation of perilipin 2 (PLIN2), the most abundant lipid droplet-associated protein in steatotic liver, protects mice from diet-induced NAFLD. However, the mechanisms underlaying this protection are unclear. We tested the contributions of ATGL and lipophagy mediated lipolysis to reduced hepatic TAG in mice with liver-specific PLIN2 deficiency (PLIN2LKO) fed a Western-type diet for 12 weeks. We observed enhanced autophagy in the absence of PLIN2, as determined by ex vivo p62 flux, as well as increased p62- and LC3-positive autophagic vesicles in PLIN2LKO livers and isolated primary hepatocytes. Increased levels of autophagy correlated with significant increases in cellular fatty acid (FA) oxidation in PLIN2LKO hepatocytes. We observed that inhibition of either autophagy or ATGL blunted the increased FA oxidation in PLIN2LKO hepatocytes. Additionally, combined inhibition of ATGL and autophagy reduced FA oxidation to the same extent as treatment with either inhibitor alone. In sum, these studies show that protection against NAFLD in the absence of hepatic PLIN2 is driven by the integrated actions of both ATGL and lipophagy.

Objective Regulation of fatty acid (FA) metabolism is central to adipocyte dysfunction during diet-induced obesity (DIO). Long-chain acyl-CoA synthetase-4 (ACSL4) has been hypothesized to modulate the metabolic fates of polyunsaturated FA (PUFA), including arachidonic acid (AA), but the in vivo actions of ACSL4 are unknown. The purpose of our studies was to determine the in vivo role of adipocyte ACSL4 in regulating obesity-associated adipocyte dysfunction. Methods We developed a novel mouse model with adipocyte-specific ablation of ACSL4 (Ad-KO) using loxP Cre recombinase technology. Metabolic phenotyping of Ad-KO mice relative to their floxed littermates (ACSL4floxed) was performed, including body weight and body composition over time; insulin and glucose tolerance tests; and energy expenditure, activity, and food intake in metabolic cages. Adipocytes were isolated for ex vivo adipocyte oxygen consumption by Clark electrode and lipidomics analysis. In vitro adipocyte analysis including oxygen consumption by Seahorse and real-time PCR analysis were performed to confirm our in vivo findings. Results Ad-KO mice were protected against DIO, adipocyte death, and metabolic dysfunction. Adipocytes from Ad-KO mice fed high-fat diet (HFD) had reduced incorporation of AA into phospholipids (PL), free AA, and levels of the AA lipid peroxidation product 4-hydroxynonenal (4-HNE). Additionally, adipocytes from Ad-KO mice fed HFD had reduced p53 activation and increased adipocyte oxygen consumption (OCR), which we demonstrated are direct effects of 4-HNE on adipocytes in vitro. Conclusion These studies are the first to elucidate ACSL4's in vivo actions to regulate the incorporation of AA into PL and downstream effects on DIO-associated adipocyte dysfunction. By reducing the incorporation of AA into PL and free fatty acid pools in adipocytes, Ad-KO mice were significantly protected against HFD-induced increases in adipose and liver fat accumulation, adipocyte death, gonadal white adipose tissue (gWAT) inflammation, and insulin resistance (IR). Additionally, deficiency of adipocyte ACSL4 expression in mice fed a HFD resulted in increased gWAT adipocyte OCR and whole body energy expenditure (EE)., Highlights • ACSL4 expression is upregulated in murine white adipocytes during diet-induced obesity. • Mice with adipocyte-specific ablation of ACSL4 (Ad-KO) are protected against diet-induced obesity, adipocyte death and metabolic dysfunction. • Lipidomics profiling of isolated adipocytes from Ad-KO mice fed a high-fat diet (HFD) had reduced arachidonic acid (AA) in phospholipids. • Adipocytes from Ad-KO mice fed HFD had reduced free AA and levels of the AA lipid peroxidation product 4-hydroxynonenal (4-HNE). • Adipocytes from Ad-KO mice fed HFD had reduced p53 activation and increased adipocyte oxygen consumption (OCR). • P53 activation and inhibited adipocyte OCR are direct effects of 4-HNE on adipocytes in vitro.

Rapid growth in America’s economic inequality and endemic disadvantages among racial minorities have deepened fears about unequal political influence. From separate studies, it appears that the gov...

When black Americans and white Americans want the president to do different things, who wins? When low-income earners prefer different government action than do middle and high-income earners, whose preferences are reflected in presidential behavior? Recent studies show that congressional behavior often most closely follows the preferences of the white and the wealthy, but we know relatively little about presidential behavior. Since the president and Congress make policy together, it is important to understand the extent of political equality in presidential behavior. We examine the degree to which presidents have provided equal representation to these groups over the past four decades. We compare the preferences of these groups for federal spending in various budget domains to presidents’ subsequent budget proposals in those domains from 1974 to 2010. Over this period, presidents’ proposals aligned more with the preferences of whites and high-income earners. However, Republican presidents are driving thi...

Objective The family of acyl-CoA synthetase enzymes (ACSL) activates fatty acids within cells to generate long chain fatty acyl CoA (FACoA). The differing metabolic fates of FACoAs such as incorporation into neutral lipids, phospholipids, and oxidation pathways are differentially regulated by the ACSL isoforms. In vitro studies have suggested a role for ACSL5 in triglyceride synthesis; however, we have limited understanding of the in vivo actions of this ACSL isoform. Methods To elucidate the in vivo actions of ACSL5 we generated a line of mice in which ACSL5 expression was ablated in all tissues (ACSL5−/−). Results Ablation of ACSL5 reduced ACSL activity by ∼80% in jejunal mucosa, ∼50% in liver, and ∼37% in brown adipose tissue lysates. Body composition studies revealed that ACSL5−/−, as compared to control ACSL5loxP/loxP, mice had significantly reduced fat mass and adipose fat pad weights. Indirect calorimetry studies demonstrated that ACSL5−/− had increased metabolic rates, and in the dark phase, increased respiratory quotient. In ACSL5−/− mice, fasting glucose and serum triglyceride were reduced; and insulin sensitivity was improved during an insulin tolerance test. Both hepatic mRNA (∼16-fold) and serum levels of fibroblast growth factor 21 (FGF21) (∼13-fold) were increased in ACSL5−/− as compared to ACSL5loxP/loxP. Consistent with increased FGF21 serum levels, uncoupling protein-1 gene (Ucp1) and PPAR-gamma coactivator 1-alpha gene (Pgc1α) transcript levels were increased in gonadal adipose tissue. To further evaluate ACSL5 function in intestine, mice were gavaged with an olive oil bolus; and the rate of triglyceride appearance in serum was found to be delayed in ACSL5−/− mice as compared to control mice. Conclusions In summary, ACSL5−/− mice have increased hepatic and serum FGF21 levels, reduced adiposity, improved insulin sensitivity, increased energy expenditure and delayed triglyceride absorption. These studies suggest that ACSL5 is an important regulator of whole-body energy metabolism and ablation of ACSL5 may antagonize the development of obesity and insulin resistance., Graphical abstract, Highlights • Role of acyl CoA synthetase 5 (ACSL5) in systemic metabolism was studied in an ACSL5 deficient mouse. • ACSL5 deficiency reduced total ACSL activity in liver, intestine, and brown adipose tissue. • ACSL5 deficient mice had increased hepatic and circulating FGF21 expression and energy expenditure. • ACSL5 deficient mice demonstrated delayed triglyceride absorption.

This review examines how legislators' race and ethnicity affect the representation of racial and ethnic minorities' interests and priorities in the mass public, how these legislators affect the political participation of these groups, how the presence of these candidates affects voter decision making, and how their prevalence impacts the composition of the parties and the nature of public policy. It also points to new directions and opportunities for scholarship on why minority legislators matter for American politics.

Reelection-minded officials have motivations to represent some of their constituents more than others when casting roll-call votes. In particular, reelection seekers have incentives to appeal to those with greater “voting power” (Bartels 1998): those who are likely to vote, are not strongly predisposed to vote for one of the parties, and are members of large groups within a particular constituency. We present two novel findings stemming from these incentives. First, we find that those with greater voting power tend to enjoy better policy representation. Second, the rewards of voting are greater for those belonging to groups with more voting power. Since voting power varies across racial/ethnic and income lines, these findings hold significant normative implications.

In the first article to evaluate the equality of dyadic policy representation experienced by women, we assess the congruence between U.S. House members' roll-call votes and the policy preferences of their female and male constituents. Employing two measures of policy representation, we do not find a gender gap in dyadic policy representation. However, we uncover a sizeable gender gap favoring men in districts represented by Republicans, and a similarly sizeable gap favoring women in districts represented by Democrats. A Democratic majority further improves women's dyadic representation relative to men, but having a female representative (descriptive representation) does not.

The authors uncover evidence that citizens’ priorities about various spheres of legislative representation differ across demographic groups and that these differences are subsequently reflected in the in-office behavior of their elected officials. Specifically, African Americans and Latinos are less concerned than whites with policy representation—the attentiveness of elected officials to citizens’ policy preferences—but place more emphasis on their district receiving its fair share of federal money. Citizens with higher incomes place a higher priority on policy representation and less on constituency service than do those with lower incomes. Importantly, these priorities map onto their member of Congress’s behavior.

Thermoregulatory neurons in the preoptic area of the anterior hypothalamus (POA) form synaptic networks, which affect responses that regulate body temperature. To characterize these pathways of activation, projections to effector control areas, like the dorsomedial hypothalamus (DMH), require labeling in live tissue slices. Traditional fluorescent dyes label axon terminals near an injection site, but unfortunately, also that of nearby fibers of passage. Here, we describe a novel methodology for retrograde labeling of neurons in vitro, which will allow for further electrophysiological recording. To determine if POA neurons project to the DMH, we have used nanometer-sized, gold nanoprobes, which provide for specific neuronal entry, via synapses in close proximity to the injection site. Upon neuronal entry, these nanoprobe complexes diffuse to the soma, where they are readily visualized and quantified. We found that conjugation of these gold nanoprobes with VGLUT-2 antibodies and polyethyleneimine (PEI) facilitates neuronal entry and a high level of labeling efficacy. This novel method, adapted from emerging cancer therapy technologies, is highly specific for determining axon terminal projections within particular neuronal populations, while maintaining neuronal viability for targeted live cell electrophysiological recording.

The authors relate the racial composition of districts to five measures of legislative activity and position in the 101st to 106th Congresses: bill introduction, colleague cosponsorship, bill passage, committee portfolio, and party leadership. The authors find that African American constituents generally are represented by less active and less well-positioned legislators on four of the five measures. They also explore the origin of these disparities. Two of the disparities (bill passage and party leadership) are partly explained by the tendency of districts with larger African American populations to be less electorally competitive. A third disparity (committee portfolio) is accounted for by the tendency of larger African American populations to be represented by African American members of Congress.

Do government policy decisions impact citizens’ involvement in politics? Using panel data, we assess the extent to which variation in levels of political participation among citizens between 2000 and 2004 is linked to the nexus of citizens’ preferences and government policy. We show that two policy decisions—military intervention in Iraq and the Bush tax cuts—did affect citizens’ subsequent political participation, mobilizing the biggest policy winners and galvanizing the greatest policy losers to increase their political activity. However, the mechanism that explains increased participation differs between winners and losers. We also uncover evidence that policy realization, or citizens’ retrospective perceptions of how well a policy played out, and political knowledge both moderate the effect of policy winning and losing on political participation.

Objective. Previous models of roll-call voting have either ignored the role of legislator ideology or have employed questionable measures of it. A defensible measure of legislator ideology is needed. Methods. This study surveys former members of Congress (MCs) to obtain a new measure of legislator preferences. The measure has several attractive properties, appears to be valid, and is unique compared to a preference measure others have used. Results. Validating the measure in a model of roll-call voting reveals that the importance of legislators' ideologies is similar to that of their party affiliations. Conclusions. A useful measure of legislators' ideologies can be generated using a postretirement instrument.

We compare the ideological proximity of Latinos and whites to their Members of Congress (MCs), demonstrating the degree to which Latinos are underrepresented compared to whites. We show how this representation gap varies with group differences in electoral turnout and income, district ethnic composition, and MCs' ethnicity and party affiliation. We find that Latinos' unequal representation is not simply a function of the group's numerical minority status. Concentrating Latinos in congressional districts does not necessarily translate into more equal representation. However, several factors can enhance the equality of Latinos' representation—participation in elections and representation by both Latinos and Democrats.

Citizens contribute to the process of democratic accountability by acquiring information about their elected officials' behavior, comparing this information to their expectations regarding substantive representation, and voting in elections based on the result of this comparison. However, citizens possess varying levels of information about, and different expectations of, Representatives' voting behavior. This raises the possibility that some citizens are more likely to hold their Members of Congress (MCs) accountable than others. We find that there are substantial racial disparities in democratic accountability between whites and African Americans and that these disparities stem from African Americans' relative difficulty acquiring information about their MCs' voting behavior, as well as from this group's unique expectations of their MCs. These racial differences in information and expectations are exacerbated by descriptive representation, but not because descriptively represented African Americans are ...

Does vigorous electoral competition help to convert citizens' preferences into government action? No, concludes a series of theoretical and empirical studies conducted over the last 35 years. If these findings are correct, efforts to enhance competition such as depoliticizing the redistricting process and achieving greater equity in campaign spending, while perhaps beneficial in other respects, will not improve government responsiveness. However, these studies are limited by a shortage of data, by biased measures of district competitiveness, and by their conceptualization of responsiveness. Using both cross-sectional and fixed-effects modeling frameworks, this study finds that in recent years elected officials who represent more competitive districts are indeed more responsive to their constituents' preferences.

Though many studies have focused on African Americans' turnout levels in descriptively represented electoral districts, few have examined the composition of African-American turnout in these districts, compared to districts that are not descriptively represented. This study contends that descriptive representation should conditionally affect African Americans' political participation, given preference heterogeneity among this group. It then examines the extent to which the ideological orientations of African Americans condition the effect of their Representative's race in the 104th House on their probability of participating in the 1996 national election. The study finds that when liberal African Americans are descriptively represented, they are more likely to vote, while moderate and conservative African Americans are less likely to vote. These findings not only help to resolve prior studies' disparate conclusions concerning descriptive representation's participatory effects, but they also show that descriptive representation affects which African Americans' interests are communicated to elected officials through voting.

Political scientists have long known that the equal representation of states in the U.S. Senate and the placement of state lines might disadvantage politically relevant groups, granting some citizens greater voting weight in the chamber. Yet we lack systematic, longitudinal evidence that identifies the groups disadvantaged by Senate malapportionment, the sources of this disadvantage, and probes the policy consequences. In this article, I compare each state's liberalism and racial composition with its relative voting weight in the Senate over time. Additionally, I examine whether roll-call coalitions in the Senate map onto these patterns of state ideology and racial composition.

1. The pineal hormone melatonin influences thermoregulation in many species, but the mechanism of action is unknown. 2. We tested whether melatonin could act directly on the primary thermoregulatory control center in the preoptic area and anterior hypothalamus (PO/AH), using a white-footed mouse tissue slice preparation. 3. PO/AH neurons were classified according to their thermosensitivity, then treated with 1 μM melatonin. 4. Thirty percent of warm-sensitive and 41% of temperature-insensitive neurons showed significant changes in firing rate during melatonin treatment. 5. While there was no correlation between responses to melatonin and thermosensitivity, these results constitute the first evidence that melatonin acts directly on PO/AH thermoregulatory neurons.

Studies of political participation and representation often contend that elected officials respond more to the preferences of voters than those of nonvoters, but seldom test this claim. This is a critical assumption because if true, biases in who participates will lead to biased representation. Office holders might respond disproportionately to voters’ preferences because voters tend to select like-minded representatives, voters tend to communicate their preferences more, and only voters can reelect representatives. We find that voter preferences predict the aggregate roll-call behavior of Senators while nonvoter preferences do not. We also present evidence supporting the three explanations advanced to account for the preferential treatment of voters.

1. Hypothalamic thermosensitive neurons are important in the integrative regulation of body temperature. In addition to receiving afferent thermal input, their activity correlates with the stimulation of thermoregulatory mechanisms. 2. While cold sensitivity is synaptically mediated, warm sensitivity depends on inherent cellular responses. Warm sensitive neurons may also respond to other homeostatic variations, hormones, and endogenous mediators. 3. In contrast to peripheral thermoresponsiveness, which depends on conductance changes that regulate membrane potential, hypothalamic warm sensitivity relies on regulating the prepotential phase of the action potential. 4. Additionally, the recent morphologic characterization of these neurons supports the criterion for warm sensitivity.

Early work suggested that dietary cholesterol increased plasma total cholesterol concentrations in humans. Given the relationship between elevated plasma cholesterol concentrations and cardiovascular disease risk, dietary guidelines have consistently recommended limiting food sources of cholesterol. Current intakes are approaching recommended levels. Recently there have been calls to reassess the importance of continuing to recommend limiting dietary cholesterol. Over the past 10 years, there have been a limited number of studies addressing this issue. Striking among these studies is the high degree of variability in background diet, study subject characteristics, and study design. Within the context of current levels of dietary cholesterol intake, the effect on plasma lipid concentrations, with primary interest in LDL cholesterol concentrations, is modest and appears to be limited to population subgroups. In these cases, restrictions in dietary cholesterol intake are likely warranted. The biological determinants of interindividual variability remain a relatively understudied area.

Background In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. Methods We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties. Results In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p

Fever is thought to be initiated by pyrogenic cytokines inducing the production of prostaglandin E2 (PGE2) in the preoptic area (POA); PGE2 may act as a paracrine mediator that stimulates the neural pathways that raise body temperature. This essential role for prostaglandins in fever first was proposed 25 years ago, but the specific preoptic cell groups at which PGE2 acts and the pathways through which fever is produced remain poorly understood. To better define the role of preoptic PGE2 in fever, we developed a new method for combining acute brain injections with Fos immunohistochemistry. We microinjected a threshold dose of PGE2 to construct an anatomically detailed map of fever-producing preoptic sites. The most pyrogenic preoptic sites were clustered along the ventromedial aspect of the POA, surrounding and just anterior to the organum vasculosum of the lamina terminalis. We then used Fos immunohistochemistry to identify the pattern of neural activation induced by fever-producing preoptic injections of PGE2 and compared it with the Fos pattern seen after systemic immune stimulation. PGE2 fever was accompanied by Fos induction in the ventromedial POA and the parvicellular subnuclei of the paraventricular nucleus of the hypothalamus (PVH). In contrast to the Fos pattern seen after intravenous lipopolysaccharide administration, PGE2 injection did not induce Fos in the circumventricular organs or the magnocellular subnuclei of the PVH. These observations establish a potential site of PGE2 action during fever and help define candidate pathways through which fever occurs.

1. To study the basic mechanisms of neuronal thermosensitivity, rat hypothalamic tissue slices were used to record and compare intracellular activity of temperature-sensitive and -insensitive neurones. This study tested the hypothesis that different neuronal types have thermally dependent differences in the transient potentials that determine the interspike interval. 2. Most spontaneously firing neurones displayed depolarizing prepotentials that preceded each action potential. In warm-sensitive neurones, warming increased the rate of rise of the depolarizing prepotential which, in turn, decreased the interspike interval and increased the firing rate. In contrast, temperature had little or no effect on the rate of rise in prepotentials of temperature-insensitive neurones. 3. Prepotential depolarization can be due to increasing depolarizing conductances or decreasing hyperpolarizing conductances. These are differences in the ionic conductances responsible for prepotentials in temperature-sensitive and -insensitive neurones. In warm-sensitive neurones, the net ionic conductance decreased as the prepotential depolarized towards threshold, suggesting that the prepotential is primarily determined by a decrease in outward potassium conductances. In contrast, in low-slope temperature-insensitive neurones, the net conductance remained constant during the interspike interval, suggesting a more balanced combination of both depolarizing and hyperpolarizing conductances. 4. Transient outward potassium currents, including A-currents, are important determinants of neuronal firing rates. These currents were identified in all warm-sensitive neurones tested, as well as in many temperature-insensitive and silent neurones. Since warming increased the rates of inactivation of these currents, transient K+ currents may contribute to the temperature-dependent prepotentials of some hypothalamic neurones.

The paraventricular nucleus of the hypothalamus (PVN) is the gatekeeper to temperature-modulating hormones such as vasopressin. Indeed, it is in theory a key target region for thermoregulatory efferents of the preoptic area of the anterior hypothalamus (POAH). Although several retrograde labeling studies have identified a connection between the POAH and PVN, none have directly characterized the thermoregulatory nature of this interaction. We will identify the phenotype of these connections by injecting retrograde-labeling nanoprobes into the PVN of live tissue slices and quantified labeled POAH somas. These probes are designed for selective uptake by glutamate-releasing axon terminals, after which they diffuse rapidly to the neuron soma. Our results indicate that glutamatergic neurons do project from the POAH to the PVN. This technique will allow for further electrophysiologic studies to identify the thermosensitivity of neurons with a known connectivity and phenotype.