Transient changes in mothers' negative emotional reactivity predict changes in the intensity, persistence, and variability of their aversive behavior.

Applying theories of emotion to understanding the regulation of aversive parenting, we used microanalytic observational methods to test whether transient changes in a mother's negative emotional reactivity predict changes over time in key parameters of her moment-to-moment aversive behavior: its intensity, variability, persistence, and connection to difficult child inputs. At multiple times over 2 years, 319 divorcing mothers and their 5- to 12-year-old children were observed as they discussed mutual disagreements. Sequences of talk-turns were recorded and coded for affect and content. Relative to days when a mother was low in negative emotional reactivity, on days when she was high she displayed more intensely aversive behavior, more variable aversiveness, more transitions from average to high or low aversiveness, tendencies to remain aversive longer following spikes in her aversiveness, and difficulty maintaining low aversiveness following drops in her aversiveness. As her negative emotional reactivity increased, she went from being relatively unaffected by children's difficult behavior to being aversively reactive; from ceasing aversive sequences increasingly quickly to ceasing aversive sequences increasingly slowly; from deviating more from her nonreactive low-aversive parenting to deviating less from her reactive high-aversive parenting. Independent of stable individual differences in mothers and children, transient variations in mothers' emotional reactivity may correspond to key moment-to-moment parameters of aversive parenting, even when interactions are relatively noncontentious. The data provide a viable account of how initially transient, context-specific reactivity could initiate moment-to-moment changes in aversive patterns that in some families influence problematic family trajectories over time. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Examining Children's Problem Behaviors and Mothers' Dating for Mothers' Depressive Symptoms Following Divorce.

Although divorce is typically stressful for mothers, the formation of post-divorce dating relationships can help to ease this stress. Unfortunately, research has yet to empirically consider children's post-divorce adjustment for mothers' wellbeing leading up to and during mothers' post-divorce dating. This study addresses the following questions: 1) How do children's problem behaviors predict mothers' depressive symptoms following divorce? 2) How do children's problem behaviors predict the quality of mothers' dating relationships and the rapport between children and mothers' dating partners? 3) How do children's problem behaviors, the quality of mothers' dating relationships, child-dating partner rapport, and length of mothers' dating simultaneously impact mothers' depressive symptoms? Data for this study comes from a longitudinal investigation of recently divorced mothers and their children (N = 232). Hierarchical linear models revealed that mothers experienced more depressive symptoms when their children exhibited more internalizing behaviors. Children's internalizing behaviors were negatively associated with the quality of mothers' dating relationships. When examining these variables simultaneously, increases in children's internalizing behaviors and decreases in relationship quality predicted increases in mothers' depressive symptoms. Promoting family-level adjustment appears best for mothers' wellbeing following divorce. Other implications for post-divorce adjustment are discussed.

Expressing negative emotions to children: Mothers' aversion sensitivity and children's adjustment.

Research is unclear about when expressing negative emotions to children performs valuable socialization and regulatory functions and when, instead, it undermines children's adjustment. In this study, we isolated 1 kind of negative expression to test the aversion sensitivity hypothesis: that rapid increases in mothers' negativity as a function of increases in the aversiveness of children's behavior are uniquely problematic for children. During multiple assessments of a divorcing sample over 2 years (N = 284), 12-min interactions between mothers and their 4- to 11-year-old children were recorded. Forty-seven observed child behaviors were ranked from low to high aversive. Within-dyad changes demonstrated that mothers' general negativity-their tendency to express negative emotion at high rates-was unrelated to children's adjustment. In contrast, mothers' aversion-focused negativity-their tendency to increase negative emotional expression rapidly as the aversiveness of children's behavior increased-predicted children's poor social competence, poor emotion regulation, and externalizing behavior problems at the next assessment. The findings suggest that negative expression that reflects mothers' affective sensitivity to aversive child behavior may promote interaction patterns and adaptations in children that are particularly likely to place children at risk for adjustment problems. (PsycINFO Database Record

Consequences of Dating for Post-Divorce Maternal Well-Being.

Repartnering has been linked to health benefits for mothers, yet few studies have examined relationship quality in this context. According to the divorce-stress-adaptation perspective, relationship quality may influence the relationship between maternal well-being and dating after divorce. The current study examines the consequences of dating, relationship quality, and dating transitions (breaking up and dating new partners) on maternal well-being (negative affect and life satisfaction). Using monthly surveys completed by mothers over a two-year period after filing for divorce, we examined changes in intercepts and slopes of dating status and transitions for maternal well-being while also testing the effects of relationship quality. Mothers entering high-quality relationships were likely to report boosts in well-being at relationship initiation compared to single mothers and mothers entering low-quality relationships. Mothers entering lower-quality relationships were likely to report lower levels of well-being than single mothers. Dating transitions were associated with increases in well-being. Implications for maternal adjustment are discussed.

Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain.

Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein-protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors.

Biogenesis and subcellular organization of the magnetosome organelles of magnetotactic bacteria.

Bacterial cells, like their eukaryotic counterparts, are capable of constructing lipid-based organelles that carry out essential biochemical functions. The magnetosomes of magnetotactic bacteria are one such compartment that is quickly becoming a model for exploring the process of organelle biogenesis in bacteria. Magnetosomes consist of a lipid-bilayer compartment that houses a magnetic crystal. By arranging magnetosomes into chains within the cell, magnetotactic bacteria create an internal compass that is used for navigation along magnetic fields. Over the past decade, a number of studies have elucidated the possible factors involved in the formation of the magnetosome membrane and biomineralization of magnetic minerals. Here, we highlight some of these recent advances with a particular focus on the cell biology of magnetosome formation.

Analysis of the CtrA pathway in Magnetospirillum reveals an ancestral role in motility in alphaproteobacteria.

Developmental events across the prokaryotic life cycle are highly regulated at the transcriptional and posttranslational levels. Key elements of a few regulatory networks are conserved among phylogenetic groups of bacteria, although the features controlled by these conserved systems are as diverse as the organisms encoding them. In this work, we probed the role of the CtrA regulatory network, conserved throughout the Alphaproteobacteria, in the magnetotactic bacterium Magnetospirillum magneticum strain AMB-1, which possesses unique intracellular organization and compartmentalization. While we have shown that CtrA in AMB-1 is not essential for viability, it is required for motility, and its putative phosphorylation state dictates the ability of CtrA to activate the flagellar biosynthesis gene cascade. Gene expression analysis of strains expressing active and inactive CtrA alleles points to the composition of the extended CtrA regulon, including both direct and indirect targets. These results, combined with a bioinformatic study of the AMB-1 genome, enabled the prediction of an AMB-1-specific CtrA binding site. Further, phylogenetic studies comparing CtrA sequences from alphaproteobacteria in which the role of CtrA has been experimentally examined reveal an ancestral role of CtrA in the regulation of motility and suggest that its essential functions in other alphaproteobacteria were acquired subsequently.

"My child and I are a package deal": balancing adult and child concerns in repartnering after divorce.

Parents who repartner after divorce must decide how to balance the potentially competing demands of their own desire for adult companionship and romance with the needs of their children for parental attention and affection. In this study, the authors assessed individual differences in divorced custodial mothers' orientation toward repartnering, characterizing it as a continuum, ranging from more child focused to more adult focused. Mothers who are more adult focused tend to be older, more educated, more likely to be employed outside the home, and exiting marriages of longer duration. In addition, using longitudinal data from in-home interviews, mothers who are more adult focused reported having lower rapport with their children, spending less time in joint activities with their children, and their children in turn reported lower rapport with their mothers. Levels of adult-focused orientation are relatively stable over time but increase when mothers become involved or interested in new partners. Using longitudinal diary data over a 2-year period, the authors demonstrated that mothers who are more child focused engage in more active management of emergent relationships in repartnered families and that adult-focused and child-focused mothers respond to different concerns. Whereas all mothers become more active in managing emergent relationships when both partner and child are resisting one another, mothers with greater child focus respond more to concerns of the child, and mothers with greater adult focus respond more to the concerns of the partner. Implications for intervention with divorced families are discussed.

Additive empirical force field for hexopyranose monosaccharides.

We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the alpha- and beta-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute-water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids.

Time-dependent density functional theory/discrete reaction field spectra of open shell systems: The visual spectrum of [FeIII(PyPepS)2]- in aqueous solution.

We report the calculated visible spectrum of [FeIII(PyPepS)2]- in aqueous solution. From all-classical molecular dynamics simulations on the solute and 200 water molecules with a polarizable force field, 25 solute/solvent configurations were chosen at random from a 50 ps production run and subjected the systems to calculations using time-dependent density functional theory (TD-DFT) for the solute, combined with a solvation model in which the water molecules carry charges and polarizabilities. In each calculation the first 60 excited states were collected in order to span the experimental spectrum. Since the solute has a doublet ground state several excitations to states are of type "three electrons in three orbitals," each of which gives rise to a manifold of a quartet and two doublet states which cannot properly be represented by single Slater determinants. We applied a tentative scheme to analyze this type of spin contamination in terms of Delta and Delta transitions between the same orbital pairs. Assuming the associated states as pure single determinants obtained from restricted calculations, we construct conformation state functions (CFSs), i.e., eigenfunctions of the Hamiltonian Sz and S2, for the two doublets and the quartet for each Delta,Delta pair, the necessary parameters coming from regular and spin-flip calculations. It appears that the lower final states remain where they were originally calculated, while the higher states move up by some tenths of an eV. In this case filtering out these higher states gives a spectrum that compares very well with experiment, but nevertheless we suggest investigating a possible (re)formulation of TD-DFT in terms of CFSs rather than determinants.

Additive and Classical Drude Polarizable Force Fields for Linear and Cyclic Ethers.

Empirical force field parameters consistent with the CHARMM additive and classical Drude based polarizable force fields are presented for linear and cyclic ethers. Initiation of the optimization process involved validation of the aliphatic parameters based on linear alkanes and cyclic alkanes. Results showed the transfer to cyclohexane to yield satisfactory agreement with target data; however, in the case of cyclopentane direct transfer of the Lennard-Jones parameters was not sufficient due to ring strain, requiring additional optimization of these parameters for this molecule. Parameters for the ethers were then developed starting with the available aliphatic parameters, with the nonbond parameters for the oxygens optimized to reproduce both gas- and condensed-phase properties. Nonbond parameters for the polarizable model include the use of an anisotropic electrostatic model on the oxygens. Parameter optimization emphasized the development of transferable parameters between the ethers of a given class. The ether models are shown to be in satisfactory agreement with both pure solvent and aqueous solvation properties, and the resulting parameters are transferable to test molecules. The presented force field will allow for simulation studies of ethers in condensed phase and provides a basis for ongoing developments in both additive and polarizable force fields for biological molecules.

Electronic structure, bonding, spectroscopy and energetics of Fe-dependent nitrile hydratase active-site models.

Fe-type nitrile hydratase (NHase) is a non-heme Fe(III)-dependent enzyme that catalyzes the hydration of nitriles to the corresponding amides. Despite experimental studies of the enzyme and model Fe(III)-containing complexes, many questions concerning the electronic structure and spectroscopic transitions of the metal center remain unanswered. In addition, the catalytic mechanism of nitrile hydration has not yet been determined. We now report density functional theory (B3LYP/6-31G) calculations on three models of the Fe(III) center in the active site of NHase corresponding to hypothetical intermediates in the enzyme-catalyzed hydration of acetonitrile. Together with natural bond orbital (NBO) analysis of the chemical bonding in these active-site models and INDO/S CIS calculations of their electronic spectra, this theoretical investigation gives new insight into the molecular origin of the unusual low-spin preference and spectroscopic properties of the Fe(III) center. In addition, the low-energy electronic transition observed for the active form of NHase is assigned to a dd transition that is coupled with charge-transfer transitions involving the metal and its sulfur ligands. Calculations of isodesmic ligand-exchange reaction energies provide support for coordination of the Fe(III) center in free NHase by a water molecule rather than a hydroxide ion and suggest that the activation of the nitrile substrate by binding to the metal in the sixth coordination site during catalytic turnover cannot yet be definitively ruled out.

Theoretical investigations of the electronic structure and spectroscopy of mononuclear, non-heme [Fe-NO](6) complexes.

The unusual metal coordination and spin-state of the Fe(III) center in nitrile hydratase (NHase) has stimulated the synthesis of numerous model complexes in efforts to understand the reactivity and spectroscopic properties of the enzyme. A particular problem has been the development of model Fe(III) complexes that exhibit reversible, photolabile binding to nitric oxide (NO) in a manner similar to that observed for the NHase metal center. We now report a detailed NBO analysis of the ground-state chemical bonding in three [Fe-NO](6) complexes that exhibit different responses to irradiation, together with investigations of their spectroscopic properties using semiempirical INDO/S CI singles calculations. Our computational studies reveal a correlation between the photolability of these complexes and the existence of low-energy transitions that promote an electron into the Fe-NO pi(*) antibonding molecular orbital. In addition to providing detailed insights into how the ligand field influences the spectroscopy of these mononuclear complexes, these studies strengthen our previous conclusions regarding the role of post-translational cysteine modification in modulating the photoreactivity of the inactive, NO complex of NHase.

The role of post-translational modification in the photoregulation of Fe-type nitrile hydratase.

The inactive, nitrosyl bound form of Fe-type nitrile hydratase (NHase) contains two active site cysteine residues that are post-translationally modified to sulfenate (SO-) and sulfinate (SO2-) ligands. DFT and INDO/S calculations support the hypothesis that these unusual modifications play a key role in modulating the electronic absorption spectra and photoreactivity of the Fe(III) centre in the enzyme.

Six-year follow-up of preventive interventions for children of divorce: a randomized controlled trial.

CONTEXT: Compared with their peers with nondivorced parents, adolescents with divorced parents are more likely to have mental health problems, drop out of school, and become pregnant. The long-term effects of intervention programs for this population are unknown. OBJECTIVE: To evaluate the long-term effectiveness of 2 programs designed to prevent mental health problems in children with divorced parents. DESIGN AND SETTING: Six-year follow-up of a randomized controlled trial of 2 intervention programs (mother program: 11 group and 2 individual sessions; mother plus child program: mother program and 11 group sessions for children) and a control condition (books on postdivorce adjustment), which was conducted in a large metropolitan US city from April 1998 through March 2000. PARTICIPANTS: A total of 218 families (91% of the original sample) with adolescents aged between 15 and 19 years were reinterviewed. MAIN OUTCOME MEASURES: Externalizing and internalizing problems, diagnosed mental disorders, drug and alcohol use, and number of sexual partners. RESULTS: Eleven percent of adolescents in the mother plus child program (95% confidence interval [CI], 3.8%-18.2%) had a 1-year prevalence of diagnosed mental disorder compared with 23.5% (95% CI, 13.8%-33.2%) of adolescents in the control program (P =.007). Adolescents in the mother plus child program had fewer sexual partners (mean [SE], 0.68 [0.16]) compared with adolescents in the control program (1.65 [0.37]; P =.01). Adolescents with higher initial mental health problems whose families were in the mother plus child program had lower externalizing problems (P =.007) and fewer symptoms of mental disorder (P =.02) compared with those in the control program. Compared with controls, adolescents whose mothers participated in the mother program and who had higher initial mental health problems had lower levels of externalizing problems (P<.001); fewer symptoms of mental disorder (P =.005); and less alcohol (P =.005), marijuana (P =.02), and other drug use (P =.01). CONCLUSIONS: In adolescents of divorced parents, the mother program and the mother plus child program reduced symptoms of mental disorder; rates of diagnoses of mental disorder; levels of externalizing problems; marijuana, alcohol, and other drug use; and number of sexual partners.