Effects of Ca2+ on supramolecular aggregation of natural organic matter in aqueous solutions: A comparison of molecular modeling approaches

Natural organic matter (NOM) represents a complex molecular system that cannot be fully characterized compositionally or structurally in full atomistic detail. This makes the application of molecular modeling approaches very difficult and significantly hinders quantitative investigation of NOM properties and behavior by these otherwise very efficient computational techniques. Here we report and analyze three molecular dynamics (MD) simulations of Ca2+ complexation with NOM in aqueous solutions in an attempt to quantitatively assess possible effects of model- and system size-dependence in such simulations. Despite some obvious variations in the computed results that depend on the size of the simulated system and on the parameters of the force field models used, all three simulations are quite robust and consistent. They show Ca2+ ions associated with 35-50% of the NOM carboxylic groups at near-neutral pH and point to a strong preference for the stability of bidentate-coordinated contact ion pairs. The degree and potential mechanisms of NOM supramolecular aggregation in the presence of Ca2+ ions in solution are also assessed on a semi-quantitative level from two larger-scale MD simulations

Hydrogen bonding and coordination in normal and supercritical water from X-ray inelastic scattering

A direct measure of hydrogen bonding in water under conditions ranging from the normal state to the supercritical regime is derived from the Compton scattering of inelastically-scattered X-rays. First, we show that a measure of the number of electrons $n_e$ involved in hydrogen bonding at varying thermodynamic conditions can be directly obtained from Compton profile differences. Then, we use first-principles simulations to provide a connection between $n_e$ and the number of hydrogen bonds $n_{HB}$. Our study shows that over the broad range studied the relationship between $n_e$ and $n_{HB}$ is linear, allowing for a direct experimental measure of bonding and coordination in water. In particular, the transition to supercritical state is characterized by a sharp increase in the number of water monomers, but also displays a significant number of residual dimers and trimers.Comment: 14 pages, 5 figures, 1 tabl

Cocaine Disrupts Pup-Induced Maternal Behavior in Juvenile and Adult Rats

Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure. Originally published Neurotoxicology and Teratology, Vol. 29, No. 6, Nov 200

Long-Lasting Consequences of Neonatal Maternal Separation on Social Behaviors in Ovariectomized Female Mice

Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty

Molecular dynamics simulation of humic substances

© 2014, Orsi. Humic substances (HS) are complex mixtures of natural organic material which are found almost everywhere in the environment, and particularly in soils, sediments, and natural water. HS play key roles in many processes of paramount importance, such as plant growth, carbon storage, and the fate of contaminants in the environment. While most of the research on HS has been traditionally carried out by conventional experimental approaches, over the past 20 years complementary investigations have emerged from the application of computer modeling and simulation techniques. This paper reviews the literature regarding computational studies of HS, with a specific focus on molecular dynamics simulations. Significant achievements, outstanding issues, and future prospects are summarized and discussed

Effects of an Early Handling-Like Procedure and Individual Housing on Anxiety-Like Behavior in Adult C57BL/6J and DBA/2J Mice

Manipulations of rearing conditions have been used to examine the effects of early experience on adult behavior with varying results. Evidence suggests that postnatal days (PND) 15–21 are a time of particular susceptibility to environmental influences on anxiety-like behavior in mice. To examine this, we subjected C57BL/6J and DBA/2J mice to an early handling-like procedure. Pups were separated from dams from PND 12–20 for 30 minutes daily or received standard care. On PND 21, pups were weaned and either individually- or group- housed. On PND 60, anxiety-like behavior was examined on the elevated zero-maze. Although individually- housed animals took longer to enter an open quadrant of the maze, they spent more time in the open than group-housed animals. Additionally, we observed a trend of reduced anxiety-like behavior in C57BL/6J, but not DBA/2J mice that underwent the handling-like procedure

Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review

Abstract BACKGROUND: The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder. METHODS: A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed, with the combination of the words 'aripiprazole' and 'bipolar'. RESULTS: The search returned 184 articles and was last updated on 15 April 2009. An additional search included repositories of clinical trials and previous systematic reviews specifically in order to trace unpublished trials. There were seven placebo-controlled randomised controlled trials (RCTs), six with comparator studies and one with add-on studies. They assessed the usefulness of aripiprazole in acute mania, acute bipolar depression and during the maintenance phase in comparison to placebo, lithium or haloperidol. CONCLUSION: Aripiprazole appears effective for the treatment and prophylaxis against mania. The data on bipolar depression are so far negative, however there is a need for further study at lower dosages. The most frequent adverse effects are extrapyramidal signs and symptoms, especially akathisia, without any significant weight gain, hyperprolactinaemia or laboratory test changes

Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression

Fractional anisotropy anomalies occurring in the white matter tracts in the brains of depressed patients may reflect microstructural changes underlying the pathophysiology of this disorder. We conducted a meta-analysis of fractional anisotropy abnormalities occurring in major depressive disorder using voxel-based diffusion tensor imaging studies. Using the Embase, PubMed and Google Scholar databases, 89 relevant data sets were identified, of which 7 (including 188 patients with major depressive disorder and 221 healthy controls) met our inclusion criteria. Authors were contacted to retrieve any additional data required. Coordinates were extracted from clusters of significant white matter fractional anisotropy differences between patients and controls. Relevant demographic, clinical and methodological variables were extracted from each study or obtained directly from authors. The meta-analysis was carried out using Signed Differential Mapping. Patients with depression showed decreased white matter fractional anisotropy values in the superior longitudinal fasciculus and increased fractional anisotropy values in the fronto-occipital fasciculus compared to controls. Using quartile and jackknife sensitivity analysis, we found that reduced fractional anisotropy in the left superior longitudinal fasciculus was very stable, with increases in the right fronto-occipital fasciculus driven by just one study. In conclusion, our meta-analysis revealed a significant reduction in fractional anisotropy values in the left superior longitudinal fasciculus, which may ultimately play an important role in the pathology of depression