The maintenance of oocytes in the mammalian ovary involves extreme protein longevity.

Women are born with all of their oocytes. The oocyte proteome must be maintained with minimal damage throughout the woman's reproductive life, and hence for decades. Here we report that oocyte and ovarian proteostasis involves extreme protein longevity.

Medical marijuana laws and mental health in the United States.

The consequences of legal access to medical marijuana for individuals' well-being are controversially assessed. We contribute to the discussion by evaluating the impact of the introduction of medical marijuana laws across US states on self-reported mental health considering different motives for cannabis consumption. Our analysis is based on BRFSS survey data from close to eight million respondents between 1993 and 2018 that we combine with information from the NSDUH to estimate individual consumption propensities.

KCNA2 IgG autoimmunity in neuropsychiatric diseases.

Background: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice.

Design / Methods: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses.

Does the Dream of Home Ownership Rest Upon Biased Beliefs? A Test Based on Predicted and Realized Life Satisfaction.

The belief that home ownership makes people happy is probably one of the most widespread intuitive theories of happiness. However, whether it is accurate is an open question. Based on individual panel data, we explore whether home buyers systematically overestimate the life satisfaction associated with moving to their privately owned property.

Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment.

Full-grown oocytes are transcriptionally silent and must stably maintain the messenger RNAs (mRNAs) needed for oocyte meiotic maturation and early embryonic development. However, where and how mammalian oocytes store maternal mRNAs is unclear. Here, we report that mammalian oocytes accumulate mRNAs in a mitochondria-associated ribonucleoprotein domain (MARDO).

Swiss Municipal Data Merger Tool: Open-source Software for the Compilation of Longitudinal Municipal-level Data.

The Swiss Municipal Data Merger Tool (Swiss MDMT) offers a solution to a frequent data management problem encountered when compiling longitudinal datasets involving Swiss municipalities as the observational units. Due to municipal mergers, the number of municipalities in Switzerland declined from 3,095 in 1960 to 2,202 in 2020. As a consequence, manually securing the correct spatial reference when merging historical cross-sectional data is tedious and time-consuming.

Analysis of protein-DNA interactions in chromatin by UV induced cross-linking and mass spectrometry.

Protein-DNA interactions are key to the functionality and stability of the genome. Identification and mapping of protein-DNA interaction interfaces and sites is crucial for understanding DNA-dependent processes. Here, we present a workflow that allows mass spectrometric (MS) identification of proteins in direct contact with DNA in reconstituted and native chromatin after cross-linking by ultraviolet (UV) light.

Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome.

Chromatin-remodelling complexes of the SWI/SNF family function in the formation of nucleosome-depleted, transcriptionally active promoter regions (NDRs). In the yeast Saccharomyces cerevisiae, the essential SWI/SNF complex RSC contains 16 subunits, including the ATP-dependent DNA translocase Sth1. RSC removes nucleosomes from promoter regions and positions the specialized +1 and -1 nucleosomes that flank NDRs.

Structure of the transcription coactivator SAGA.

Gene transcription by RNA polymerase II is regulated by activator proteins that recruit the coactivator complexes SAGA (Spt-Ada-Gcn5-acetyltransferase) and transcription factor IID (TFIID). SAGA is required for all regulated transcription and is conserved among eukaryotes. SAGA contains four modules: the activator-binding Tra1 module, the core module, the histone acetyltransferase (HAT) module and the histone deubiquitination (DUB) module.

Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts.

Smoking bans, cigarette prices and life satisfaction.

The consequences of tobacco control policies for individual welfare are difficult to assess, even more so when related consumption choices challenge people's willpower. We therefore evaluate the impact of smoking bans and cigarette prices on subjective well-being by analyzing data for 40 European countries and regions between 1990 and 2011. We exploit the staggered introduction of bans and apply an imputation strategy to study the effect of anti-smoking policies on people with different propensities to smoke.

Limited Self-control, Obesity, and the Loss of Happiness.

Is obesity the consequence of an optimally chosen lifestyle or do people consume too much relative to their long-term preferences? The latter perspective accepts that people might face self-control problems when exposed to the immediate gratification from food. We exploit unique survey data for Switzerland in multinomial logit and ordered probit regressions to study (i) the covariates of obesity including indicators of self-control and (ii) the consequences of obesity on the subjective well-being of people with limited willpower. Our main finding is that obesity decreases the well-being of individuals who report having limited self-control, but not otherwise.

pvsR: An Open Source Interface to Big Data on the American Political Sphere.

Digital data from the political sphere is abundant, omnipresent, and more and more directly accessible through the Internet. Project Vote Smart (PVS) is a prominent example of this big public data and covers various aspects of U.S.

Multimerization of Drosophila sperm protein Mst77F causes a unique condensed chromatin structure.

Despite insights on the cellular level, the molecular details of chromatin reorganization in sperm development, which involves replacement of histone proteins by specialized factors to allow ultra most condensation of the genome, are not well understood. Protamines are dispensable for DNA condensation during Drosophila post-meiotic spermatogenesis. Therefore, we analyzed the interaction of Mst77F, another very basic testis-specific protein with chromatin and DNA as well as studied the molecular consequences of such binding.

Polycomb-dependent H3K27me1 and H3K27me2 regulate active transcription and enhancer fidelity.

H3K27me3 is deposited at promoters by the preferential association of Polycomb repressive complex 2 (PRC2) with CpG-rich DNA elements regulating development by repressing gene transcription. H3K27 is also present in mono- and dimethylated states; however, the functional roles of H3K27me1 and H3K27me2 deposition remain poorly characterized. Here, we show that PRC2 activity is not only associated with H3K27me3 but also regulates all forms of H3K27 methylation in a spatially defined manner, contributing to different genomic functions in mouse embryonic stem cells.

Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome.

Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Although genetic and cell biological aspects have been elucidated, the molecular details of HP1 binding to H3K9me3 nucleosomes are unknown. Using a combination of NMR spectroscopy and biophysical measurements on fully defined recombinant experimental systems, we demonstrate that H3K9me3 works as an on/off switch regulating distinct binding modes of hHP1β to the nucleosome.

Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events.

Phosphorylation of Ser10 of histone H3 regulates chromosome condensation and transcriptional activity. Using time-resolved, high-resolution NMR spectroscopy, we demonstrate that histone H3 Ser10 phosphorylation inhibits checkpoint kinase 1 (Chk1)- and protein kinase C (PKC)-mediated modification of Thr11 and Thr6, the respective primary substrate sites of these kinases. On unmodified H3, both enzymes also target Ser10 and thereby establish autoinhibitory feedback states on individual H3 tails.

Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells.

Background: Polycomb group (PcG) genes code for chromatin multiprotein complexes that are responsible for maintaining gene silencing of transcriptional programs during differentiation and in adult tissues. Despite the large amount of information on PcG function during development and cell identity homeostasis, little is known regarding the dynamics of PcG complexes and their role during terminal differentiation.

Results: We show that two distinct polycomb repressive complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes.

Chromatin affinity purification and quantitative mass spectrometry defining the interactome of histone modification patterns.

DNA and histone modifications direct the functional state of chromatin and thereby the readout of the genome. Candidate approaches and histone peptide affinity purification experiments have identified several proteins that bind to chromatin marks. However, the complement of factors that is recruited by individual and combinations of DNA and histone modifications has not yet been defined.

Histone methylation by PRC2 is inhibited by active chromatin marks.

The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2 Nurf55-Su(z)12 submodule.

Prosocial Motivation and Blood Donations: A Survey of the Empirical Literature.

Recent shortages in the supply of blood donations have renewed the interest in how blood donations can be increased temporarily. We survey the evidence on the role of financial and other incentives in eliciting blood donations among donors who are normally willing to donate pro bono. We present the predictions from different empirical/psychological-based theories, with some predicting that incentives are effective while others predict that incentives may undermine prosocial motivation.

Free cholesterol testing as a motivation device in blood donations: evidence from field experiments.

Background: Health tests are often seen as promising donor incentives to improve the supply of blood. However, systematic behavioral evidence on donor recruitment is scarce.

Study Design And Methods: To study the effectiveness of a free cholesterol test in attracting new donors and motivating previous donors, two field experiments were conducted.

Enhanced expression of hypersensitive alpha4* nAChR in adult mice increases the loss of midbrain dopaminergic neurons.

We describe an inducible genetic model for degeneration of midbrain dopaminergic neurons in adults. In previous studies, knock-in mice expressing hypersensitive M2 domain Leu9'Ser (L9'S) alpha4 nicotinic receptors (nAChR) at near-normal levels displayed dominant neonatal lethality and dopaminergic deficits in embryonic midbrain, because the hypersensitive nAChR is excitotoxic. However, heterozygous L9'S mice that retain the neomycin resistance cassette (neo) in a neighboring intron express low levels of the mutant allele (approximately 25% of normal levels), and these neo-intact mice are therefore viable and fertile.

Establishment and characterization of two immortalized cell lines of the osteoblastic lineage.

Osteoblastic cells were cloned by culturing rat calvariae cells in agarose in the presence of TGF-beta and EGF. Two bone cell lines were established by immortalizing such an osteoblastic clonal cell population by the introduction of the avian v-mycOK10 gene in the form of a mouse ecotropic retrovirus. Although originating from the same clonal cell population, the two lines exhibited somewhat differing properties.