Trait and state positive emotional experience in schizophrenia: a meta-analysis

Background

Prior meta-analyses indicated that people with schizophrenia show impairment in trait hedonic capacity but retain their state hedonic experience (valence) in laboratory-based assessments. Little is known about what is the extent of differences for state positive emotional experience (especially arousal) between people with schizophrenia and healthy controls. It is also not clear whether negative symptoms and gender effect contribute to the variance of positive affect.

Methods and Findings

The current meta-analysis examined 21 studies assessing state arousal experience, 40 studies measuring state valence experience, and 47studies assessing trait hedonic capacity in schizophrenia. Patients with schizophrenia demonstrated significant impairment in trait hedonic capacity (Cohen’s d = 0.81). However, patients and controls did not statistically differ in state hedonic (valence) as well as exciting (arousal) experience to positive stimuli (Cohen’s d = −0.24 to 0.06). They also reported experiencing relatively robust state aversion and calmness to positive stimuli compared with controls (Cohen’s d = 0.75, 0.56, respectively). Negative symptoms and gender contributed to the variance of findings in positive affect, especially trait hedonic capacity in schizophrenia.

Conclusions

Our findings suggest that schizophrenia patients have no deficit in state positive emotional experience but impairment in “noncurrent” hedonic capacity, which may be mediated by negative symptoms and gender effect.     

Synthesis and pharmacology of new enantiopure delta(3)-4-arylkainoids

Seven delta(3)-4-arylkainoids possessing various 4-position aromatic and heteroaromatic groups were synthesized and their apparent affinities were measured in order to explore the influences of 4-position electron density and stereochemistry on receptor affinity and specificity. Kainoids 1a-f were shown to be selective agonists at the NMDA receptor and the electron rich furanyl and thienyl analogues exhibited the highest affinities. Naphthylkainoid 1g proved to be a nonselective antagonist at the iGluRs.     

Synergistic Tissue Counterstaining and Image Segmentation Techniques for Accurate, Quantitative Immunohistochemistry

Quantitative analysis of digitized IHC-stained tissue sections is increasingly used in research studies and clinical practice. Accurate quantification of IHC staining, however, is often complicated by conventional tissue counterstains caused by the color convolution of the IHC chromogen and the counterstain. To overcome this issue, we implemented a new counterstain, Acid Blue 129, which provides homogeneous tissue background staining. Furthermore, we combined this counterstaining technique with a simple, robust, fully automated image segmentation algorithm, which takes advantage of the high degree of color separation between the 3-amino-9-ethyl-carbazole (AEC) chromogen and the Acid Blue 129 counterstain. Rigorous validation of the automated technique against manual segmentation data, using Ki-67 IHC sections from rat C6 glioma and β-amyloid IHC sections from transgenic mice with amyloid precursor protein (APP) mutations, has shown the automated method to produce highly accurate results compared with ground truth estimates based on the manually segmented images. The synergistic combination of the novel tissue counterstaining and image segmentation techniques described in this study will allow for accurate, reproducible, and efficient quantitative IHC studies for a wide range of antibodies and tissues. (J Histochem Cytochem 56:873–880, 2008)     

Transgenic tomato plants expressing an <Emphasis Type="Italic">Arabidopsis</Emphasis> thionin (<Emphasis Type="Italic">Thi2.1</Emphasis>) driven by fruit-inactive promoter battle against phytopathogenic attack

Tomato is one of the most important crop plants; however, attacks by pathogens can cause serious losses in production. In this report, we explore the potential of using the Arabidopsis thionin (Thi2.1) gene to genetically engineer enhanced resistance to multiple diseases in tomato. Potential thionin toxicity in fruits was negated by the use of a fruit-inactive promoter to drive the Thi2.1 gene. In transgenic lines containing RB7/Thi2.1, constitutive Thi2.1 expression was detected in roots and incidentally in leaves, but not in fruits. Disease assays revealed that the transgenic lines that were tested conferred significant levels of enhanced resistance to bacterial wilt (BW) and Fusarium wilt (FW). Further studies indicated that BW disease progression in transgenic lines was delayed by a systemic suppression of bacterial multiplication. By adopting a safe genetic engineering strategy, the present investigation is another step forward demonstrating thionin practicality in crop protection.     

Leucine-rich repeat kinase 2 induces α-synuclein expression via the extracellular signal-regulated kinase pathway

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of autosomal-dominant Parkinson's disease (PD). The second known autosomal-dominant PD gene (SNCA) encodes α-synuclein, which is deposited in Lewy bodies, the neuropathological hallmark of PD. LRRK2 contains a kinase domain with homology to mitogen-activated protein kinase kinase kinases (MAPKKKs) and its activity has been suggested to be a key factor in LRRK2-associated PD. Here we investigated the role of LRRK2 in signal transduction pathways to identify putative PD-relevant downstream targets. Over-expression of wild-type [wt]LRRK2 in human embryonic kidney HEK293 cells selectively activated the extracellular signal-regulated kinase (ERK) module. PD-associated mutants G2019S and R1441C, but not kinase-dead LRRK2, induced ERK phosphorylation to the same extent as [wt]LRRK2, indicating that this effect is kinase-dependent. However, ERK activation by mutant R1441C and G2019S was significantly slower than that for [wt]LRRK2, despite similar levels of expression. Furthermore, induction of the ERK module by LRRK2 was associated to a small but significant induction of SNCA, which was suppressed by treatment with the selective MAPK/ERK kinase inhibitor U0126. This pathway linking the two dominant PD genes LRRK2 and SNCA may offer an interesting target for drug therapy in both familial and sporadic disease.     

Formononetin,an isoflavone,relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways

We evaluated the vasorelaxation effects of formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved. Cumulative administration of formononetin, genistein, daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 μM) and methylene blue (10 μM) suppressed formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOS^Ser1177 protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 μM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 μM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 μM, an estrogen receptor (ERα/ERβ) antagonist) or mifepristone (10 μM, a progesterone receptor antagonist). In single aortic smooth muscle cells, formononetin caused opening of iberiotoxin-sensitive Ca²⁺-activated K⁺ (BK_Ca) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K⁺ (K_ATP) channels. Thus, our results suggest that formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BK_Ca and K_ATP channels.     

The sequence of the nucleotides at the alpha-sarcin cleavage site in rat 28 S ribosomal ribonucleic acid

The sequence of the 521 nucleotides at the 3' end of a rat 28 S rRNA gene was determined. The region encompasses the site of cleavage of 28 S rRNA by the cytotoxin alpha-sarcin. The toxin hydrolyzes a phosphodiester bond on the 3' side of a guanine residue 393 nucleotides from the 3' end. The alpha-sarcin domain is composed of a purine-rich sequence of 14 highly conserved nucleotides.     

Recent advances in heme-protein sensors

In recent years, an increasing number of proteins have been discovered which utilize heme cofactors to sense oxygen, carbon monoxide and nitric oxide. The identification and characterization of these proteins are revising our understanding of heme-mediated allostery first established in the early 1960s. Biochemical and structural studies are revealing new mechanisms for heme-driven conformational changes distinct from the classical hemoglobin model.     

In vitro generation of specific deletions in DNA cloned in M13 vectors using synthetic oligodeoxyribonucleotides: mutants in the 5''-flanking region of the yeast alcohol dehydrogenase II gene.

Deletion mutants are particularly useful in defining the boundaries of noncoding genetic functions. Such mutants can be precisely generated using synthetic oligodeoxyribonucleotides as mutagens. In this paper we describe the application of this method to recombinant DNA cloned in a phage M13-derived vector. The mutagenic oligodeoxyribonucleotides, 20 and 21 nucleotides in length, were used to delete a tract of 20 dA-dT base-pairs and an adjacent 22 base-pair perfect dyad from the ADR3 locus, the 5'-flanking regulatory region of the ADR2 gene, of Saccharomyces cerevisiae with high efficiency.     

The C4 and Slp genes of the complement region of the murine H-2 major histocompatibility complex

Recent analyses, at the protein and DNA levels of structure, of the murine complement components C4 and the closely related sex-limited protein, Slp have led to new insights into the H-2/S region-linked C4 and Slp genes and their products. The primary products are 200 000 Da precursors which are cleaved, intracellularly and extracellularly, into the the mature alpha-beta-gamma-subunit molecules of plasma. Precursor order of subunits is beta-alpha-gamma; a complementary DNA clone spanning the alpha-gamma junction has been extensively analysed. The C-terminal of the alpha-chain is of particular interest because of post-secretion processing which differentiates 'secreted' and 'plasma' forms of C4, both apparently functional, and because allelic variants of C4 and the Slp protein, which differ substantially in molecular masses, owe their differences principally to different levels of glycosylation of the alpha-chain. Allelic variations in rate of C4 synthesis (C4-high compared with C4-low) have been analysed in cultures of hepatocytes and macrophages. Three distinct modes of genetic regulation of the expression of the Slp protein have been identified.