Putting the affect into affective polarisation.

While many believe that affective polarisation poses a significant threat to democratic stability, the definition and operationalisation of the concept varies greatly. This leads to conceptual slippage as well as imprecise tests of the causes and consequences of affective polarisation. In order to clearly identify and target its micro-foundations, we must understand the degree to which political divides are, in fact, affective. In this paper, we do so. We begin by delineating affective polarisation, a social divide that is purportedly distinct from policy-based disagreements. Subsequently, we explore the influence of emotions in politics, including how affect is conceptualised within the framework of polarisation. Where possible, our literature review is supplemented with analyses of existing datasets to support our points. The paper concludes by proposing a series of questions emotion researchers could address in the study of polarisation.

Inconsistent and very weak evidence for a direct association between childhood personality and adult ideology.

OBJECTIVE: We add depth and breadth to the study of the childhood personality-adult ideology link with additional data, measures, and measurement approaches. BACKGROUND: Past research in (political) psychology has put forward that individual differences in psychological needs shape ideology. Most evidence supporting this claim is cross-sectional. Two previous longitudinal studies showed preliminary evidence that childhood personality traits linked to negativity bias correlate with political ideology in adulthood, yet these studies have limitations. METHODS: We report the results from two longitudinal studies (combined N = 13,822) conducted in the United Kingdom that measure childhood personality (5-11 years old) and political ideology from puberty (age 16) to early (age 26) and middle adulthood (age 42). RESULTS: We find very weak and inconsistent evidence that childhood personality traits related to negativity bias are directly associated with general conservatism, social conservatism, or economic conservatism across different stages of adulthood. Across the board, Bayes Factors most often indicate strong evidence for the null hypothesis. CONCLUSION: We offer evidence that the results of previous research are not as robust or as consistent as scholars in the extant literature presume. Our findings call for more, not less, research on the link between childhood personality and political ideology.

Accelerating the Shuttling in Hydrogen-Bonded Rotaxanes: Active Role of the Axle and the End Station.

The relation between the chemical structure and the mechanical behavior of molecular machines is of paramount importance for a rational design of superior nanomachines. Here, we report on a mechanistic study of a nanometer scale translational movement in two bistable rotaxanes. Both rotaxanes consist of a tetra-amide macrocycle interlocked onto a polyether axle. The macrocycle can shuttle between an initial succinamide station and a 3,6-dihydroxy- or 3,6-di-tert-butyl-1,8-naphthalimide end stations. Translocation of the macrocycle is controlled by a hydrogen-bonding equilibrium between the stations. The equilibrium can be perturbed photochemically by either intermolecular proton or electron transfer depending on the system. To the best of our knowledge, utilization of proton transfer from a conventional photoacid for the operation of a molecular machine is demonstrated for the first time. The shuttling dynamics are monitored by means of UV-vis and IR transient absorption spectroscopies. The polyether axle accelerates the shuttling by ∼70% compared to a structurally similar rotaxane with an all-alkane thread of the same length. The acceleration is attributed to a decrease in activation energy due to an early transition state where the macrocycle partially hydrogen bonds to the ether group of the axle. The dihydroxyrotaxane exhibits the fastest shuttling speed over a nanometer distance (τshuttling ≈ 30 ns) reported to date. The shuttling in this case is proposed to take place via a so-called harpooning mechanism where the transition state involves a folded conformation due to the hydrogen-bonding interactions with the hydroxyl groups of the end station.

Inter-individual differences in CpG methylation at D4Z4 correlate with clinical variability in FSHD1 and FSHD2.

Facioscapulohumeral muscular dystrophy (FSHD: MIM#158900) is a common myopathy with marked but largely unexplained clinical inter- and intra-familial variability. It is caused by contractions of the D4Z4 repeat array on chromosome 4 to 1-10 units (FSHD1), or by mutations in the D4Z4-binding chromatin modifier SMCHD1 (FSHD2). Both situations lead to a partial opening of the D4Z4 chromatin structure and transcription of D4Z4-encoded polyadenylated DUX4 mRNA in muscle. We measured D4Z4 CpG methylation in control, FSHD1 and FSHD2 individuals and found a significant correlation with the D4Z4 repeat array size. After correction for repeat array size, we show that the variability in clinical severity in FSHD1 and FSHD2 individuals is dependent on individual differences in susceptibility to D4Z4 hypomethylation. In FSHD1, for individuals with D4Z4 repeat arrays of 1-6 units, the clinical severity mainly depends on the size of the D4Z4 repeat. However, in individuals with arrays of 7-10 units, the clinical severity also depends on other factors that regulate D4Z4 methylation because affected individuals, but not non-penetrant mutation carriers, have a greater reduction of D4Z4 CpG methylation than can be expected based on the size of the pathogenic D4Z4 repeat array. In FSHD2, this epigenetic susceptibility depends on the nature of the SMCHD1 mutation in combination with D4Z4 repeat array size with dominant negative mutations being more deleterious than haploinsufficiency mutations. Our study thus identifies an epigenetic basis for the striking variability in onset and disease progression that is considered a clinical hallmark of FSHD.

Hemizygosity for SMCHD1 in Facioscapulohumeral Muscular Dystrophy Type 2: Consequences for 18p Deletion Syndrome.

Facioscapulohumeral muscular dystrophy (FSHD) is most often associated with variegated expression in somatic cells of the normally repressed DUX4 gene within the D4Z4-repeat array. The most common form, FSHD1, is caused by a D4Z4-repeat array contraction to a size of 1-10 units (normal range 10-100 units). The less common form, FSHD2, is characterized by D4Z4 CpG hypomethylation and is most often caused by loss-of-function mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene on chromosome 18p. The chromatin modifier SMCHD1 is necessary to maintain a repressed D4Z4 chromatin state. Here, we describe two FSHD2 families with a 1.2-Mb deletion encompassing the SMCHD1 gene. Numerical aberrations of chromosome 18 are relatively common and the majority of 18p deletion syndrome (18p-) cases have, such as these FSHD2 families, only one copy of SMCHD1. Our finding therefore raises the possibility that 18p- cases are at risk of developing FSHD. To address this possibility, we combined genome-wide array analysis data with D4Z4 CpG methylation and repeat array sizes in individuals with 18p- and conclude that approximately 1:8 18p- cases might be at risk of developing FSHD.

Complexes of a naphthalimide photoacid with organic bases, and their excited-state dynamics in polar aprotic organic solvents.

Complex formation and intermolecular excited-state proton transfer (ESPT) between a dihydroxy-1,8-naphthalimide photoacid and organic bases are investigated in polar aprotic solvents. First, quantum chemical calculations are used to explore the acid-base and spectroscopic properties and to identify energetically favorable complexes. The two hydroxyl groups of the photoacid enable stepwise formation of 1 : 1 and 1 : 2 complexes. Weak bases exhibit only hydrogen-bonding interactions whereas strong bases are able to deprotonate one of the hydroxyl groups resulting in strong negative cooperativity (K1≫ 4K2) in the formation of the 1 : 2 complex. Time-resolved fluorescence studies of the complexes provide strong indications of a three-step dissociation process. The species involved in the model are: a hydrogen-bonded complex, a hydrogen-bonded ion pair, a solvent separated ion pair, and a free ion pair.

Tone in politics is not systematically related to macro trends, ideology, or experience.

What explains the variation in tone in politics? Different literatures argue that changes in the tone of politicians reflect changes in the economy, general language, well-being, or ideology. So far, these claims have been empirically tested only in isolation, in single country studies, or with a small subset of indicators. We offer an overarching view by modelling the use of tone in European national parliaments in 7 countries across 30 years. Using a semi-supervised sentiment-topic model to measure polarity and arousal in legislative debates, we show in a preregistered multiverse analysis that the tone in legislative debates is not systematically related to previously claimed factors. We also replicate the absence of such systematic relationships using national leader speeches and parties' election manifestos. There is also no universal trend towards more negativity or emotionality in political language. Overall, our results highlight the importance of multi-lingual and cross-country multiverse analyses for generalizing findings on emotions in politics.

Facing emotional politicians: Do emotional displays of politicians evoke mimicry and emotional contagion?

Emotional displays of politicians can be persuasive. According to prominent psychological theories, we can easily "catch" the emotional displays of others through mimicry and emotional contagion. Do these processes work for politicians too, or is it conditional on what voters think of the politician making the display? In a preregistered within-subjects laboratory experiment, participants observed images of neutral and manipulated emotional displays of politicians. We measured emotional mimicry (facial electromyography) and emotional contagion (self-reports). We do not find evidence for the matched motor hypothesis. Our findings are in line with the emotional mimicry in social context model. Namely, we find that the happy displays of in-party politicians elicit congruent facial activity (a positive facial index). Furthermore, the displays of the out-party politicians do not elicit mimicry, but instead our findings suggest a reactive response: Participants smiled in response to angry out-party politicians. The self-reported emotions indicated a small effect of emotional contagion. Taken together, our study provides insights in how voters are emotionally affected by politicians' emotional displays and highlights that our polarized prior beliefs color our emotional responses to politics. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring: Can the regulations be relaxed?

After the introduction of clozapine eight Finnish patients died after developing agranulocytosis. Clozapine was withdrawn from the market and only reintroduced with strict mandatory white blood cell monitoring as long as treatment lasts and thresholds at which clozapine must be discontinued definitively. The fear of agranulocytosis and the need for intensive blood monitoring is the single most important barrier for prescribers and patients alike and leads to underprescription of the only effective and approved medication for treatment-resistant schizophrenia. We summarize evidence that the risk of agranulocytosis is smaller than perceived at the time of reintroduction, is concentrated in the first 18 weeks of treatment, is not greater than with other antipsychotics thereafter and that frequent blood monitoring has not demonstrably decreased the rate of agranulocytosis. Therefore we propose 1) mandatory monitoring of the absolute neutrophil count (ANC) exclusively during the first 18 weeks of clozapine treatment, 2) that thereafter the prescriber and the well-informed patient decide together about further monitoring frequency, 3) that clozapine treatment must be stopped if the ANC falls below 1.0 × 109/L. Continuation of clozapine or a rechallenge are possible if prescriber and patient determine that the benefits outweigh the risks. 4) National registries which control the haematologic monitoring are unnecessary and do not help to reduce clozapine-induced agranulocytosis. They should at least be restricted to the first 18 weeks of clozapine use.

Time-resolved vibrational spectroscopy of a molecular shuttle.

Time-resolved vibrational spectroscopy is used to investigate the inter-component motion of an ultraviolet-triggered two-station molecular shuttle. The operation cycle of this molecular shuttle involves several intermediate species, which are observable in the amide I and amide II regions of the mid-IR spectrum. Using ab initio calculations on specific parts of the rotaxane, and by comparing the transient spectra of the normal rotaxane with that of the N-deuterated version, we can assign the observed vibrational modes of each species occurring during the shuttling cycle in an unambiguous way. The complete time- and frequency-dependent data set is analyzed using singular value decomposition (SVD). Using a kinetic model to describe the time-dependent concentrations of the transient species, we derive the absorption spectra associated with each stage in the operation cycle of the molecular shuttle, including the recombination of the charged species.

The complicated but solvable threat-politics relationship.

Popular models on the threat-politics association suggest that threats cause right-wing political preferences. Failed replications, crossnational variation, and examples of threats causing left-wing preferences suggest this relationship is more complicated. We introduce a model of the reciprocal threat-politics relationship that reconciles prior conflicting findings and raises new questions.

Two-dimensional vibrational spectroscopy of rotaxane-based molecular machines.

It has recently become possible to synthesize mechanical devices the size of a single molecule. Although it is tempting to regard such molecular machines as nanoscale versions of their macroscopic analogs, many notions from macroscopic mechanics no longer apply at a molecular level. For instance, the concept of viscous friction is meaningless for a molecular machine because the size of the solvent molecules that cause the friction is comparable to that of the machine itself. Furthermore, in many cases, the interactions between a molecular machine and its surroundings are comparable to the force driving the machine. As a result, a certain amount of intrinsic randomness exists in the motion of molecular machines, and the details of their mechanics are largely unknown. For a detailed understanding of the mechanical behavior of molecular machines, experiments that probe their motion on an ultrafast time scale, such as two-dimensional (2D) vibrational spectroscopy, are essential. This method uses coupling between vibrational modes in a molecule to investigate the molecular conformation. The coupling shows up as off-diagonal peaks in a 2D graph of the vibrational response of the molecule, analogous to the spin coupling observed in multidimensional NMR spectroscopy. Both spin coupling and vibrational coupling are sensitive probes of the molecular conformation, but 2D vibrational spectroscopy shows orders of magnitude better time resolution than NMR. In this Account, we use 2D vibrational spectroscopy to study molecular machines based on rotaxanes. These devices consist of a linear thread and a macrocycle that is noncovalently locked onto the thread. In the rotaxanes we study, the macrocycle and the thread both contain CO and NH groups. By determining the coupling between the stretching modes of these goups from the cross peaks in the 2D spectrum, we directly and quantitatively probe the relative position and orientation of the macrocycle and the thread for both a small model rotaxane and a rotaxane-based molecular shuttle. Our results demonstrate the feasibility of using time-resolved 2D-IR experiments to measure externally triggered structural changes of molecular devices with subpicosecond time resolution. We can observe each of the elementary events that underlie the mechanical motion separately. With this ability to investigate the nature of the mechanical motions at the molecular level and with unprecedented time resolution, we expect that 2D-IR spectroscopy on molecular machines will lead to new insights into their function.

Spectroscopic study of the authentic emitter of AMPPD chemiluminescence in alkaline aqueous solution.

To design more effective CIEEL (chemically initiated electron exchange luminescence) systems demands a complete picture of the dynamics of the chemiluminescence, which is often a challenge. In this work, photoluminescence of the methyl m-oxybenzoate anion - the authentic emitter of AMPPD (3-[2-spiroadamantane]-4-methoxy-4-[3-phosphoryloxy]-phenyl-1,2-dioxetane) in aqueous solvent has been studied. Combining the effect of solvent properties, e.g. pH value, and spectroscopic studies employing steady-state and ultrafast time-resolved emission and absorption and (1)H NMR techniques, a novel mechanism is proposed. We conclude that the deviation of emission peaks between chemiluminescence and photoluminescence of the authentic emitter of AMPPD i.e. the methyl m-oxybenzoate anion, in alkaline aqueous solvents is due to its hydrolysis, rather than the hydrogen-bonding effect as has been assumed so far. Besides, the hydrogen-bonding is suggested to play a key role in significantly decreasing the chemiluminescence yield of AMPPD in aqueous solution by shortening the lifetime of the excited authentic emitter to 10 ps order of magnitude - three orders of magnitude shorter than the previously reported value ( approximately 10 ns). These results shed light on the chemiluminescence dynamics of AMPPD and facilitate the design of more effective CIEEL systems.

Yikes! Are we disgusted by politicians?

In the political domain, disgust is primarily portrayed as an emotion that explains individual differences in pathogen avoidance. We hypothesized that political rhetoric accusing opponents of moral transgressions also elicits disgust responses. In this registered report, we present the results from a laboratory experiment. We find that participants self-report higher disgust and have stronger physiological (Levator labii) responses to pictures of out-party leaders compared with in-party leaders. Participants also report higher disgust in response to moral violations of in-party leaders. There is more suggestive evidence that in-party leaders evoke more labii activity when they commit moral violations than when out-party leaders do. The impact of individual differences in moral disgust and partisanship strength is very limited to absent. Intriguingly, on average, the physiological and self-reported disgust responses to the treatment are similar, but individuals differ in whether their response is physiological or cognitive. This motivates further theorizing regarding the concordance of emotional responses.

Conservatives and liberals have similar physiological responses to threats.

About a decade ago, a study documented that conservatives have stronger physiological responses to threatening stimuli than liberals. This work launched an approach aimed at uncovering the biological roots of ideology. Despite wide-ranging scientific and popular impact, independent laboratories have not replicated the study. We conducted a pre-registered direct replication (n = 202) and conceptual replications in the United States (n = 352) and the Netherlands (n = 81). Our analyses do not support the conclusions of the original study, nor do we find evidence for broader claims regarding the effect of disgust and the existence of a physiological trait. Rather than studying unconscious responses as the real predispositions, alignment between conscious and unconscious responses promises deeper insights into the emotional roots of ideology.

Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb).

Multiple osteochondromas (MO) is an autosomal dominant skeletal disease characterized by the formation of multiple cartilage-capped bone tumors growing outward from the metaphyses of long tubular bones. MO is genetically heterogeneous, and is associated with mutations in Exostosin-1 (EXT1) or Exostosin-2 (EXT2), both tumor-suppressor genes of the EXT gene family. All members of this multigene family encode glycosyltransferases involved in the adhesion and/or polymerization of heparin sulfate (HS) chains at HS proteoglycans (HSPGs). HSPGs have been shown to play a role in the diffusion of Ihh, thereby regulating chondrocyte proliferation and differentiation. EXT1 is located at 8q24.11-q24.13, and comprises 11 exons, whereas the 16 exon EXT2 is located at 11p12-p11. To date, an EXT1 or EXT2 mutation is detected in 70-95% of affected individuals. EXT1 mutations are detected in +/-65% of cases, versus +/-35% EXT2 mutations in MO patient cohorts. Inactivating mutations (nonsense, frame shift, and splice-site mutations) represent the majority of MO causing mutations (75-80%). In this article, the clinical aspects and molecular genetics of EXT1 and EXT2 are reviewed together with 895 variants in MO patients. An overview of the reported variants is provided by the online Multiple Osteochondromas Mutation Database (http://medgen.ua.ac.be/LOVD).

A stepwise increase in recombinant human growth hormone dosing during puberty achieves improved pubertal growth: a National Cooperative Growth Study report.

UNLABELLED: The magnitude of the pubertal growth spurt contributes to adult height. Children treated with increased doses of recombinant human growth hormone (rhGH) during puberty have shown improved near adult height (NAH) outcomes that varied by treatment duration. METHODS: Males, in a single clinic, treated with a prepubertal dose of rhGH (0.3 mg/kg/wk) received 0.1 mg/kg/wk dose increases with successive Tanner stages up to 0.6 mg/kg/wk. Changes in height and height SDS from pubertal onset to NAH were assessed in patients attaining NAH after > or =3 years (n = 23) and > or =4 years (n = 16). Using ANCOVA, outcomes were compared to closely matched patients (n = 758) from the National Cooperative Growth Study treated with a fixed dose (0.3 mg/kg/wk) throughout puberty. RESULTS: Compared to matched patients, a 3.6 cm greater increase in mean height gain and a 0.49 greater increase in mean height SDS (p <0.0001) during puberty was observed in patients attaining NAH after > or =3 years. Corresponding values were 3.9 cm and 0.54 (p <0.0001) in patients attaining NAH after > or =4 years. CONCLUSION: Stepwise increases in rhGH improved pubertal height gain when compared to a fixed dose and may represent an alternate approach to managing the patient during puberty.

Genome-wide linkage scan in Dutch hereditary non-BRCA1/2 breast cancer families identifies 9q21-22 as a putative breast cancer susceptibility locus.

Breast cancer accounts for over 20% of all female cancers. A positive family history remains one of the most important risk factors for the disease, with first-degree relatives of patients having a twofold elevated risk. Known breast cancer susceptibility genes such as BRCA1 and BRCA2 explain only 20-25% of this risk, suggesting the existence of other breast cancer susceptibility genes. Here, we report the results of a genome-wide linkage scan in 55 high-risk Dutch breast cancer families with no mutations in BRCA1 and BRCA2. Twenty-two of these families were also part of a previous linkage study by the Breast Cancer Linkage Consortium. In addition, we performed CGH analyses in 61 tumors of these families and 31 sporadic tumors. Three regions were identified with parametric HLOD scores >1, and three with nonparametric LOD scores >1.5. Upon further marker genotyping for the candidate loci, and the addition of another 30 families to the analysis, only the locus on chromosome 9 (9q21-22, marker D9S167) remained significant, with a nonparametric multipoint LOD score of 3.96 (parametric HLOD 0.56, alpha = 0.18). With CGH analyses we observed preferential copy number loss at BAC RP11-276H19, containing D9S167 in familial tumors as compared to sporadic tumors (P < 0.001). Five candidate genes were selected from the region around D9S167 and their coding regions subjected to direct sequence analysis in 16 probands. No clear pathogenic mutations were found in any of these genes.