Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS)

We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined “Reward Deficiency Syndrome” (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS?) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.     

Possible dysregulation of chaperon and metabolic proteins in cystic fibrosis bronchial tissue

Cystic fibrosis (CF) is an autosomal recessive disease due to mutations of the CF transmembrane conductance regulator gene. A systematic approach to generate a protein expressional pattern in CF bronchial tissue has not been performed so far. It was the aim of this hypothesis-generating study to construct differential proteomes of bronchial biopsies in controls (n = 8) and CF patients (n = 9). Biopsies (pools of three per patient) were taken; proteins were extracted and run on 2-DE with subsequent in-gel digestion and mass spectrometrical identification and quantification of proteins using specific software. Three hundred sixty-six protein spots were identified and compared between groups. Following an approach for multiple testing correction, the chaperone 75 kDa glucose-regulated protein and ubiquinol-cytochrome c reductase complex core protein I and one form of nidogen, a pseudogene of aconitase 2, were increased in CF (p < 0.005). Aberrant protein levels may reflect molecular changes of CF as well as CF-linked inflammation, infection and cellular stress response.     

Discovery of novel steroidal histamine H3 receptor antagonists/inverse agonists

Emerging from an HTS campaign, novel steroid-based histamine H₃ receptor antagonists were identified and characterized. Structural moieties of the hit compounds were combined to improve binding affinities which resulted in compound 4 as lead molecule. During the lead optimization due to the versatile modifications of diamino steroid derivatives, several in vitro potent compounds with subnanomolar binding affinities to histamine H₃ receptors were found. The unfavorable binding to rat muscarinic receptors was successfully reduced by tuning the basicity. Compound 20 showed significant in vivo activity in the rat dipsogenia model and could serve as a pharmacological tool in the future.     

Redox regulation of free amino acid levels in Arabidopsis thaliana

Abiotic stresses induce oxidative stress, which modifies the level of several metabolites including amino acids. The redox control of free amino acid profile was monitored in wild‐type and ascorbate or glutathione deficient mutant Arabidopsis thaliana plants before and after hydroponic treatment with various redox agents. Both mutations and treatments modified the size and redox state of the ascorbate (AsA) and/or glutathione (GSH) pools. The total free amino acid content was increased by AsA, GSH and H₂O₂ in all three genotypes and a very large (threefold) increase was observed in the GSH‐deficient pad2‐1 mutant after GSH treatment compared with the untreated wild‐type plants. Addition of GSH reduced the ratio of amino acids belonging to the glutamate family on a large scale and increased the relative amount of non‐proteinogenic amino acids. The latter change was because of the large increase in the content of alpha‐aminoadipate, an inhibitor of glutamatic acid (Glu) transport. Most of the treatments increased the proline (Pro) content, which effect was due to the activation of genes involved in Pro synthesis. Although all studied redox compounds influenced the amount of free amino acids and a mostly positive, very close (r > 0.9) correlation exists between these parameters, a special regulatory role of GSH could be presumed due to its more powerful effect. This may originate from the thiol/disulphide conversion or (de)glutathionylation of enzymes participating in the amino acid metabolism.     

Status signalling in male but not in female Eurasian Tree Sparrows Passer montanus

Male ornaments, such as plumage coloration, frequently serve as signals. The signalling function of similar ornaments in females has, however, received much less attention despite the fact that conspicuousness of their ornaments is often comparable to those of males. In this study we tested the signalling function of a plumage trait present in both sexes in the Eurasian Tree Sparrow Passer montanus. The black throat patch has been repeatedly found to have a signal function in the closely related House Sparrow Passer domesticus, where only males bear the ornamental trait. However, the function of the black throat patch in the females of Passer species that have sexually monomorphic ornament expression has never, to our knowledge, been considered. We investigated the outcomes of aggressive encounters in foraging flocks of free‐living Tree Sparrows, and assessed whether throat patch size and measurements of body size predicted fighting success in these flocks. We found that male throat patch size predicted fighting success against both male and female opponents. However, female throat patch size did not correlate with fighting success against either sex. Among the morphological traits studied, wing length was the best predictor of fighting success in females. Our findings suggest a status signalling function of throat patch size in males but not in females, although further experimental studies are necessary to corroborate these correlative results.     

Size matters for lice on birds: Coevolutionary allometry of host and parasite body size

Body size is one of the most fundamental characteristics of all organisms. It influences physiology, morphology, behavior, and even interspecific interactions such as those between parasites and their hosts. Host body size influences the magnitude and variability of parasite size according to Harrison's rule (HR: positive relationship between host and parasite body sizes) and Poulin's Increasing Variance Hypothesis (PIVH: positive relationship between host body size and the variability of parasite body size). We analyzed parasite–host body size allometry for 581 species of avian lice (～15% of known diversity) and their hosts. We applied phylogenetic generalized least squares (PGLS) methods to account for phylogenetic nonindependence controlling for host and parasite phylogenies separately and variance heterogeneity. We tested HR and PIVH for the major families of avian lice (Ricinidae, Menoponidae, Philopteridae), and for distinct ecological guilds within Philopteridae. Our data indicate that most families and guilds of avian lice follow both HR and PIVH; however, ricinids did not follow PIVH and the “body lice” guild of philopterid lice did not follow HR or PIVH. We discuss mathematical and ecological factors that may be responsible for these patterns, and we discuss the potential pervasiveness of these relationships among all parasites on Earth.     

荧光假单胞菌ZX对采后锦橙绿霉病的防治及其抑菌机制

【目的】采后柑橘极易受指状青霉(Penicillium digitatum)侵染而发生严重的绿霉病腐烂,生物防治因具有安全、有效、环保等特点近年来备受关注。论文旨在研究荧光假单胞菌(Pseudomonas fluorescens)ZX对采后柑橘绿霉病的防治效果,揭示P.fluorescensZX对P.digitatum可能存在的作用机制。【方法】以"北碚447"锦橙果实为试材,先分别接种20μL拮抗菌培养液、滤液(培养液离心后,上清经0.22μm滤膜过滤)、菌悬液(培养液离心后,菌体用无菌水反复洗涤并用无菌水重悬)和热杀死液(培养液高温高压灭菌),2 h后接种20μL P. digitatum孢子悬浮液(1×10~4spores/m L),所有果实于20oC、90%相对湿度环境下恒温恒湿培养8 d后,测定果实的发病率和病斑直径;制备柑橘皮培养基,进行平板抑菌试验,探索P. fluorescens ZX对P. digitatum孢子发芽情况的影响;采用两板对扣法和生物熏蒸法研究P.fluorescensZX挥发性次级代谢产物的抑菌作用;利用插入式细胞培养皿等分析P.fluorescensZX和P.digitatum之间竞争的营养物质;同时,测定P.fluorescensZX的生长曲线,利用结晶紫染色法评估P. fluorescens ZX的生物膜形成能力。【结果】P. fluorescens ZX不同处理液之间对采后锦橙绿霉病的作用效果差异显著,菌悬液抑菌效果最好,经菌悬液处理的果实,发病率和病斑直径分别仅为40.83%和1.78 cm;不论是在柑橘皮固体培养基上对峙培养还是在液体培养基中混合培养,菌悬液和原液的作用效果较好,固体平板上,相对抑制率达到了35%–45%,液体培养基中,P. digitatum孢子12 h后的发芽率不超过27%;P. fluorescens ZX产生的挥发性物质具有抑菌作用,经P. fluorescensZX熏蒸处理的锦橙果实,发病率和病斑直径都显著降低;营养竞争试验结果表明,P. fluorescens ZX能更快速有效地消耗柑橘皮培养基中的营养,并和P. digitatum竞争葡萄糖、果糖、蔗糖、天冬氨酸、苏氨酸、丝氨酸、亮氨酸、精氨酸和脯氨酸等营养物质;同时,P. fluorescens ZX生命力强,培养4 h后即进入对数生长期,约24 h后形成成熟的生物膜。【结论】P. fluorescens ZX可能通过抑制P. digitatum孢子发芽、营养与空间竞争、形成生物膜、产生抑菌物质等方式抑制P.digitatum的生长繁殖,有效防治采后锦橙绿霉病。