RNA-seq transcriptional profiling of Herbaspirillum seropedicae colonizing wheat (Triticum aestivum) roots.

Herbaspirillum seropedicae is a diazotrophic and endophytic bacterium that associates with economically important grasses promoting plant growth and increasing productivity. To identify genes related to bacterial ability to colonize plants, wheat seedlings growing hydroponically in Hoagland's medium were inoculated with H. seropedicae and incubated for 3 days. Total mRNA from the bacteria present in the root surface and in the plant medium were purified, depleted from rRNA and used for RNA-seq profiling. RT-qPCR analyses were conducted to confirm regulation of selected genes. Comparison of RNA profile of root attached and planktonic bacteria revealed extensive metabolic adaptations to the epiphytic life style. These adaptations include expression of specific adhesins and cell wall re-modeling to attach to the root. Additionally, the metabolism was adapted to the microxic environment and nitrogen-fixation genes were expressed. Polyhydroxybutyrate (PHB) synthesis was activated, and PHB granules were stored as observed by microscopy. Genes related to plant growth promotion, such as auxin production were expressed. Many ABC transporter genes were regulated in the bacteria attached to the roots. The results provide new insights into the adaptation of H. seropedicae to the interaction with the plant.

Comparatively preserved impulse control in late-onset opiate users.

RATIONALE: A substantial literature indicates that in alcohol addiction aspects of impulsive decision-making are typical of individuals with an early onset of addictive behaviour problems. It is not known whether the same applies to opiate addiction, and this insight has important theoretical and clinical implications. OBJECTIVES: This study aims to examine the relationship between age at onset of addictive behaviour problems and decision-making in opiate addiction. METHODS: Ninety-three opiate-dependent, treatment-seeking individuals were divided in three groups, early, late and intermediate onset of problems, and completed impulsivity questionnaires and delay discounting and gambling tasks. RESULTS: Individuals with a late onset of opiate problems (25 years or above) had lower delay discounting rates than individuals with early (18 years or less) or intermediate onset. There were no differences in performance on the gambling tasks. Late-onset individuals were older and had shorter drug histories, but there was no relationship between either age or length of exposure to opiates and delay discounting rates. CONCLUSIONS: In keeping with previous studies in alcohol addiction, these findings support the notion of at least two distinct subgroups of opiate-dependent individuals, characterised by a different onset of problems, different propensity to impulsive behaviour and perhaps distinct mechanisms leading to addiction.

Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis.

INTRODUCTION: It is widely assumed within the accumulated literature that neuropsychological function is commonly impaired as a consequence of chronic opioid use. METHOD: Quantitative and systematic review of the literature on the neuropsychology of chronic opioid use using the meta-analysis of observational studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. RESULTS: This meta-analysis suggests that chronic opioid exposure is associated with deficits across a range of different neuropsychological domains. However, the only domains where meta-analysis suggests robust impairment were those of verbal working memory, cognitive impulsivity (risk taking) and cognitive flexibility (verbal fluency). The magnitude of effect across these cognitive domains was medium according to Cohen's benchmark criteria. DISCUSSION: This analysis highlighted methodological problems present in the literature used and the value of utilising meta-analytic techniques to help further elucidate the neuropsychological consequences of chronic opioid use from 'core' addiction phenotypes.

Identical sequence patterns in the ends of exons and introns of human protein-coding genes

Intron splicing is one of the most important steps involved in the maturation process of a pre-mRNA. Although the sequence profiles around the splice sites have been studied extensively, the levels of sequence identity between the exonic sequences preceding the donor sites and the intronic sequences preceding the acceptor sites has not been examined as thoroughly. In this study we investigated identity patterns between the last 15 nucleotides of the exonic sequence preceding the 5' splice site and the intronic sequence preceding the 3' splice site in a set of human protein-coding genes that do not exhibit intron retention. We found that almost 60% of consecutive exons and introns in human protein-coding genes share at least two identical nucleotides at their 3' ends and, on average, the sequence identity length is 2.47 nucleotides. Based on our findings we conclude that the 3' ends of exons and introns tend to have longer identical sequences within a gene than when being taken from different genes. Our results hold even if the pairs are non-consecutive in the transcription order.

Risky decision-making predicts short-term outcome of community but not residential treatment for opiate addiction. Implications for case management.

BACKGROUND: Opiate addiction is associated with decision-making deficits and we previously showed that the extent of these impairments predicts aspects of treatment outcome. Here we aimed to establish whether measures of decision-making performance might be used to inform placement matching. METHODS: Two groups of opiate dependent individuals, one receiving treatment in a community setting (n=48) and one in a residential setting (n=32) were administered computerised tests of decision-making, impulsivity and planning shortly after the beginning of treatment, to be followed up three months into each programme. RESULTS: In the community sample, performance on the decision-making tasks at initial assessment predicted abstinence from illicit drugs at follow-up. In contrast, in the residential sample there was no relationship between decision-making and clinical outcome. CONCLUSIONS: Intact decision-making processes appear to be necessary for upholding a resolve to avoid taking drugs in a community setting, but the importance of these mechanisms may be attenuated in a residential treatment setting. The results support the placement matching hypothesis, suggesting that individuals with more prominent decision-making deficits may particularly benefit from treatment in a residential setting and from the inclusion of aspects of cognitive rehabilitation in their treatment programme.

Neuropsychological predictors of clinical outcome in opiate addiction.

A growing literature supports a role for neurocognitive deficits such as impaired decision-making in the development and maintenance of addictive behaviour. On the basis of these findings, it has been suggested that measures of neurocognitive functioning may be applied to the task of predicting clinical outcome in drug addiction. This in turn may have relevance for differentiating treatment based on individual patient needs. To explore this hypothesis we obtained neurocognitive measures of planning, impulsivity and decision-making from 37 opiate dependent individuals within 6 weeks of starting a community drug treatment programme and we followed them up 3 months into the programme. Performance on two tests of decision-making, but not on tests of planning, motor inhibition, reflection impulsivity or delay discounting, was found to predict abstinence from illicit drugs at 3 months with high specificity and moderate sensitivity. In particular, two thirds of the participants performing normally on the Cambridge Gamble Task and the Iowa Gambling Task, but none of those impaired on both, were abstinent from illicit drugs at follow up. Other neuropsychological, psychiatric or psychosocial factors measured in this sample did not explain this finding. The results are discussed in terms of the brain circuitry involved and the potential implications for the planning of treatment services for opiate dependence.

Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity.

It is becoming increasingly apparent that multiple functions of the frontal cortex such as inhibitory control and executive attention are likely sustained by its functionally distinct and interacting sub-regions but the precise localization of dissociable executive processes has proved difficult and controversial. In the present series of studies, we investigated the behavioural effects of bilateral excitotoxic lesions of different regions of the rat neocortex in the 5-choice serial reaction time task. Whereas lesions of the dorsal anterior cingulate cortex (ACC) impaired performance of the task as revealed by a reduction in discriminative accuracy, lesions made to distinct ventral regions of the frontal cortex showed selective deficits in inhibitory measures of control. Specifically, the infralimbic lesion produced increases in premature responding that was accompanied by fast response latencies. By comparison, the orbitofrontal lesion showed perseverative tendencies particularly when the inter-trial interval was made long and unpredictable, a challenge that would normally promote premature responding instead. These different behavioural effects following dorsal and ventral lesions of the rodent frontal cortex signifies the integrity of the frontal cortex in multiple executive mechanisms that work independently and complementarily by which performance is optimized. Furthermore, these data provide new insights into the functional organization of the rodent frontal cortex with a particular emphasis on localization of function.

Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex.

Converging lines of evidence suggest that dysfunction of brain serotonergic systems may underlie impulsive behavior. However, the nature of this deficit remains poorly understood because indirect indices of serotonin (5-HT) function are often used in clinical and experimental studies. In this investigation we measured 5-HT release directly in the prefrontal cortex of rats using in vivo microdialysis during performance of a visual attentional task. A number of performance measures were taken, including the number of premature responses made during the inter-trial interval before the onset of the visual discriminanda. This form of behavioral disinhibition was defined as impulsive, after. Lengthening the inter-trial interval increased the sensitivity of the task for detecting impulsive tendencies. Cortical levels of 5-HT and its metabolite 5-HIAA remained at pre-task levels over 1 h of task performance. By contrast, levels of dopamine (DA) and its metabolite DOPAC increased during this period. Regression analysis established a positive relationship between premature (impulsive) responses and 5-HT efflux, both under basal (r = 0.49) and task-related (r = 0.42) conditions (n = 31). No such relationship was found for prefrontal levels of DA. However, post-mortem analysis revealed that animals that were more impulsive had a higher turnover of DA in anterior cingulate, prelimbic and infralimbic cortices but no detectable abnormalities in 5-HT function. These data indicate that elevated 5-HT release in the prefrontal cortex may underlie deficits in impulse control on this task. Additionally, DA dysfunction in this region may be another, possibly independent, trait marker of impulsivity.

ExInt: an Exon Intron Database.

The Exon/Intron Database (ExInt) stores information of all GenBank eukaryotic entries containing an annotated intron sequence. Data are available through a retrieval system, as flat-files and as a MySQL dump file. In this report we discuss several implementations added to ExInt, which is accessible at http://intron.bic.nus.edu.sg/exint/newexint/exint.html.

Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task.

Recent studies have suggested a functional link between cortical cholinergic output and attentional task demands, whereby acetylcholine (ACh) release is regulated according to the outcome of ongoing behaviour. To explore this hypothesis we measured ACh efflux in the rat medial prefrontal cortex (mPFC) during between-session manipulations of the cognitive demands of an attentional task. Rats were trained to detect visual stimuli in a five-choice serial reaction time task (5-CSRTT) which involves sustained and divided attention. Following habituation to tethering and implantation with a microdialysis probe in the mPFC, rats were tested in the 5-CSRTT for three consecutive days, with different lengths of stimulus duration. During performance of the 5-CSRTT we measured robust, reproducible, task-related increases in ACh release in the mPFC across all sessions. Variations of the stimulus duration from the standard 0.5 s resulted in the predicted behavioural effects (reductions and increases in choice accuracy with 0.25 s and 5 s, respectively), but there was no evidence of either greater changes in ACh release in the more demanding condition or smaller changes in the less demanding condition. By contrast, in the session with 5-s stimulus duration there was a positive correlation between prefrontal cortical ACh efflux and the total number of trials completed. In summary, the present study shows that ACh efflux in the rat mPFC is increased during performance of a 5-CSRTT, but has found no evidence to support a specific relationship between cholinergic cortical output and attentional performance.

Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into rat prefrontal cortex.

The role in spatial divided and sustained attention of D1 and D2-like dopamine (DA) receptors in the rat prelimbic medial prefrontal cortex (mPFC) was investigated in a five-choice serial reaction time task. Rats were trained to detect brief flashes of light (0.5-0.25 sec) presented randomly in a spatial array of five apertures. When performance stabilized, animals received bilateral microinfusions of either the D1 DA receptor antagonist SCH 23390, the D1 DA receptor agonist SKF 38393, or the D2 DA antagonist sulpiride into the mPFC. Rats were divided into two groups, with low (<75% correct) and high (>75%) baseline levels of accuracy. Infusions of the D2 receptor antagonist sulpiride had no significant effect on any task variable. SCH 23390 (0.3 microg) selectively impaired the accuracy of attentional performance in rats in the high baseline condition. By contrast, SKF 38393 (0.06 microg) enhanced the accuracy of attentional performance in the low baseline condition, a lower dose (0.03 microg) also increasing the speed of making correct responses. Finally, the beneficial effects of SKF-383893 on choice accuracy were antagonized by SCH 23390 (1.0 microg). The results provide apparently the first demonstration of enhanced cognitive function after local administration of a D1 receptor agonist to the mPFC and suggest dissociable roles of D1 and D2 DA receptors of the mPFC in modulating attentional function.