Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia

Anhedonia—defined as loss of interest or pleasure—is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcers—activities with the potential to be positive experiences—is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individual’s unique set of ‘liked’ and ‘disliked’ activity words. A negative correlation was observed between anhedonia and the number of ‘liked’ activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward ‘disliked’ activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD

Cutaneous Immunization Rapidly Activates Liver Invariant Vα14 NKT Cells Stimulating B-1 B Cells to Initiate T Cell Recruitment for Elicitation of Contact Sensitivity

T cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 cells that produce IgM, which activates complement to promote T cell passage into the tissues. We now show that Vα14i NKT cells induce B-1 cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT cells. Transfers are not effective if cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 cells also reconstitutes CS responses in NKT cell–deficient mice. The B-1 cells act downstream of the Vα14i NKT cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT cells are stimulated to produce IL-4, which activates B-1 cells to produce Ag-specific IgM, subsequently needed to recruit effector T cells for elicitation of CS responses

Studies of viomycin, an anti-tuberculosis antibiotic: Copper(II) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(II) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(II)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(II)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme

Structural versatility of the quasi-aromatic Möbius type zinc(II)-pseudohalide complexes : experimental and theoretical investigations

In this contribution we report for the first time fabrication, isolation, structural and theoretical characterization of the quasi-aromatic Mobius complexes [Zn(NCS)(2)L-I] (1), [Zn-2(mu(1,1)-N-3)(2)(L-I)(2)][ZnCl3(MeOH)](2)center dot 6MeOH (2) and [Zn(NCS)L-II](2)[Zn(NCS)(4)]center dot MeOH (3), constructed from 1,2-diphenyl-1,2-bis((phenyl(pyridin-2-yl)methylene)hydrazono)ethane (L-I) or benzilbis(acetylpyridin-2-yl)methylidenehydrazone (L-II), respectively, and ZnCl2 mixed with NH4NCS or NaN3. Structures 1-3 are dictated by both the bulkiness of the organic ligand and the nature of the inorganic counter ion. As evidenced from single crystal X-ray diffraction data species 1 has a neutral discrete heteroleptic mononuclear structure, whereas, complexes 2 and 3 exhibit a salt-like structure. Each structure contains a Zn-II atom chelated by one tetradentate twisted ligand L-I creating the unusual Mobius type topology. Theoretical investigations based on the EDDB method allowed us to determine that it constitutes the quasi-aromatic Mobius motif where a metal only induces the pi-delocalization solely within the ligand part: 2.44|e| in 3, 3.14|e| in 2 and 3.44|e| in 1. It is found, that the degree of quasi-aromatic pi-delocalization in the case of zinc species is significantly weaker (by similar to 50%) than the corresponding estimations for cadmium systems - it is associated with the Zn-N bonds being more polar than the related Cd-N connections. The ETS-NOCV showed, that the monomers in 1 are bonded primarily through London dispersion forces, whereas long-range electrostatic stabilization is crucial in 2 and 3. A number of non-covalent interactions are additionally identified in the lattices of 1-3

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

ZnCoO Films Obtained at Low Temperature by Atomic Layer Deposition Using Organic Zinc and Cobalt Precursors

In this paper we report on ZnCoO thin films grown by atomic layer deposition method in reactor F-120 Satellite. ZnCoO films were grown at low temperature (T s = 160 • C) with a new zinc precursor (dimethylzinc -DMZn) and with cobalt (II) acetyloacetonate (Co(acac)2) as a cobalt precursor and deionized water as an oxygen precursor. In this paper we concentrate on the methods of homogenizing Co distribution in ZnCoO films

Population Structure of a Hybrid Clonal Group of Methicillin-Resistant Staphylococcus aureus, ST239-MRSA-III

The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec