Parental psychopathology before and after the child's diagnosis of a mental disorder: a population-based matched cohort study.

Background: More research is needed to understand psychopathology among parents of children with mental disorders in the years before and after the child is diagnosed. Here, we estimated the risk of mental disorders and psychotropic medication use in parents of children with versus without mental disorders and the temporal associations between child and parental psychopathology.

Methods: We conducted a population-based matched cohort study using Danish register data.

The role of co-occurring conditions and genetics in the associations of eating disorders with attention-deficit/hyperactivity disorder and autism spectrum disorder.

Eating disorders (EDs) commonly co-occur with other psychiatric and neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD); however, the pattern of family history and genetic overlap among them requires clarification. This study investigated the diagnostic, familial, and genetic associations of EDs with ADHD and ASD. The nationwide population-based cohort study included all individuals born in Denmark, 1981-2008, linked to their siblings and cousins.

Maternal mental disorders and neonatal outcomes: Danish population-based cohort study.

Background: Previous studies have indicated associations between maternal mental disorders and adverse birth outcomes; however, these studies mainly focus on certain types of mental disorders, rather than the whole spectrum.

Aims: We aimed to conduct a broad study examining all maternal mental disorder types and adverse neonatal outcomes which is needed to provide a more complete understanding of the associations.

Method: We included 1 132 757 liveborn singletons born between 1997 and 2015 in Denmark.

Interplay of polygenic liability with birth-related, somatic, and psychosocial factors in anorexia nervosa risk: a nationwide study.

Background: Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated.

Risk factors for anorexia nervosa: A population-based investigation of sex differences in polygenic risk and early life exposures.

Objective: To examine sex differences in risk factors for anorexia nervosa (AN).

Method: This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first.

The nucleosome family: dynamic and growing.

Ever since the discovery of the nucleosome in 1974, scientists have stumbled upon discrete particles in which DNA is wrapped around histone complexes of different stoichiometries: octasomes, hexasomes, tetrasomes, "split" half-nucleosomes, and, recently, bona fide hemisomes. Do all these particles exist in vivo? Under what conditions? What is their physiological significance in the complex DNA transactions in the eukaryotic nucleus? What are their dynamics? This review summarizes research spanning more than three decades and provides a new meaning to the term "nucleosome." The nucleosome can no longer be viewed as a single static entity: rather, it is a family of particles differing in their structural and dynamic properties, leading to different functionalities.

Nucleosome dynamics as studied by single-pair fluorescence resonance energy transfer: a reevaluation.

Accessibility of nucleosomal DNA to protein factor binding is ensured by at least three mechanisms: post-synthetic modifications to the histones, chromatin remodeling, and spontaneous unwrapping of the DNA from the histone core. We have previously used single-pair fluorescence resonance energy transfer (spFRET) experiments to investigate long-range conformational fluctuations in nucleosomal DNA (Tomschik M, Zheng H, van Holde K, Zlatanova J, Leuba SH in Proc Natl Acad Sci USA 102(9):3278-3283, 2005). Recent work has drawn attention to a major artifact in such studies due to photoblinking of the acceptor fluorophore.

Chromatin fiber structure: Where is the problem now?

The structure of the "30 nm chromatin fiber", as observed in vitro, has been a matter of controversy for 30 years. Recent studies with new and more powerful techniques give some promise for resolution. However, this will not necessarily inform us as to the in vivo structure, which may be both heteromorphic and dynamic.

Single-molecule biology: what is it and how does it work?

Biochemistry and structural biology are undergoing a dramatic revolution. Until now, we have tried to study subtle and complex biological processes by crude in vitro techniques, looking at average behaviors of vast numbers of molecules under conditions usually remote from those existing in the cell. Researchers have realized the limitations of this approach, but none other has been available.

Fast, long-range, reversible conformational fluctuations in nucleosomes revealed by single-pair fluorescence resonance energy transfer.

The nucleosome core particle, the basic repeated structure in chromatin fibers, consists of an octamer of eight core histone molecules, organized as dimers (H2A/H2B) and tetramers [(H3/H4)2] around which DNA wraps tightly in almost two left-handed turns. The nucleosome has to undergo certain conformational changes to allow processes that need access to the DNA template to occur. By single-pair fluorescence resonance energy transfer, we demonstrate fast, long-range, reversible conformational fluctuations in nucleosomes between two states: fully folded (closed), with the DNA wrapped around the histone core, or open, with the DNA significantly unraveled from the histone octamer.

Sedimentation velocity analysis of highly heterogeneous systems.

This article discusses several improvements to the van Holde-Weischet (vHW) method [Biopolymers 17 (1978) 1387] that address its capability to deal with sedimentation coefficient distributions spanning a large range of s values. The method presented here allows the inclusion of scans early and late in the experiment that ordinarily would need to be excluded from the analysis due to ultracentrifuge cell end effects. Scans late in the experiment are compromised by the loss of a defined plateau region and by back-diffusion from the bottom of the cell.

Linker histone interaction shows divalent character with both supercoiled and linear DNA.

The interaction of linker histone H1 with both linear and superhelical double-stranded DNA has been investigated at low ionic strengths. Gel mobility retardation experiments demonstrate strikingly different behavior for the two forms of DNA. First, the experiments strongly suggest that linker histone binds to superhelical DNA in a negatively cooperative mode.

Models for chromatin remodeling: a critical comparison.

Nucleosome remodeling has been shown, in many cases, to involve cis displacement of nucleosomes on the DNA. This process seems similar to the long-recognized random diffusion of nucleosomes along DNA, but the remodeling process is unidirectional and ATP dependent. Several years ago, we developed a model for nucleosome migration, based on the diffusion of "twist-defects" within the nucleosomal DNA.

Reflections on a century of protein chemistry.

The development of protein structural chemistry during the twentieth century is briefly reviewed. Emphasis is placed on certain major problems that have defined the field, and how they have been resolved, often as a consequence of technological advances. The ways in which incorrect hypotheses have affected the development of the field are also discussed.

A hypothesis concerning diffusion-limited protein-ligand interactions.

A simple assumption allows the prediction of the numerical value for a 'universal' limiting kinetic rate for wholly diffusion-limited reactions between small neutral molecules and macromolecules. This prediction is compared with appropriate experimental data for binding of ligands to myoglobin and to enzymes. It is shown that in the absence of electrostatic effects, this limit is approached but not exceeded.

Two-photon excitation microscopy of tryptophan-containing proteins.

We have examined the feasibility of observing single protein molecules by means of their intrinsic tryptophan emission after two-photon excitation. A respiratory protein from spiders, the 24-meric hemocyanin, containing 148 tryptophans, was studied in its native state under almost in vivo conditions. In this specific case, the intensity of the tryptophan emission signals the oxygen load, allowing one to investigate molecular cooperativity.

Structures of two molluscan hemocyanin genes: significance for gene evolution.

We present here the description of genes coding for molluscan hemocyanins. Two distantly related mollusks, Haliotis tuberculata and Octopus dofleini, were studied. The typical architecture of a molluscan hemocyanin subunit, which is a string of seven or eight globular functional units (FUs, designated a to h, about 50 kDa each), is reflected by the gene organization: a series of eight structurally related coding regions in Haliotis, corresponding to FU-a to FU-h, with seven highly variable linker introns of 174 to 3,198 bp length (all in phase 1).