The effect of developmental vitamin D deficiency in male and female Sprague-Dawley rats on decision-making using a rodent gambling task

Developmental vitamin D (DVD) deficiency is a plausible risk factor for schizophrenia that has been associated with behavioural alterations including disruptions in latent inhibition and response inhibition. The rodent gambling task (rGT) assesses risk-based decision-making, which is a key cognitive deficit observed in schizophrenia patients. The primary aim of this study was to examine risk-based decision-making in DVD-deficient and control rats on the rGT. We also evaluated the performance of female Sprague–Dawley rats on the rGT for the first time. Adult male and female Sprague–Dawley rats from control and vitamin D deficient dams were trained to perform the rGT in standard operant chambers and their performance and choice-preferences were assessed. Female rats were significantly faster to reach rGT training criteria compared with male rats and DVD-deficient rats were faster to reach training criteria than control animals. After reaching stable performance on the rGT DVD-deficient and control rats showed a significant preference for the optimal choice-option in the rGT, but there were no significant effects of sex or diet on these responses. DVD deficiency did not alter the decision-making processes on the rGT because no significant changes in choice-preferences were evident. This is the first study to demonstrate that once established, the performance of females is comparable to male Sprague–Dawley rats on the rGT

Script development as a ‘wicked problem’

© 2018 Intellect Ltd Article. Both a process and a set of products, influenced by policy as well as people, and incorporating objective agendas at the same time as subjective experiences, script development is a core practice within the screen industry –yet one that is hard to pin down and, to some extent, define. From an academic research perspective, we might say that script development is a ‘wicked problem’ precisely because of these complex and often contradictory aspects. Following on from a recent Journal of Screenwriting special issue on script development (2017, vol. 8:3), and in particular an article therein dedicated to reviewing the literature and ‘defining the field’, an expanded team of researchers follow up on those ideas and insights. In this article, then, we attempt to theorize script development as a ‘wicked problem’ that spans a range of themes and disciplines. As a ‘wicked’ team of authors, our expertise encompasses screenwriting theory, screenwriting practice, film and television studies, cultural policy, ethnography, gender studies and comedy. By drawing on these critical domains and creative practices, we present a series of interconnected themes that we hope not only suggests the potential for script development as a rich and exciting scholarly pursuit, but that also inspires and encourages other researchers to join forces in an attempt to solve the script development ‘puzzle’

Is there an association between metabolic syndrome and rotator cuff related shoulder pain? A systematic review

Objectives Rotator cuff related shoulder pain (RCRSP) is a common upper limb complaint. It has been suggested that this condition is more common among people with cardiometabolic risk factors. This systematic review has synthesised evidence from case-control, cross-sectional and cohort studies on the association between metabolic syndrome (MetS) and RCRSP. Design and Data Sources Five medical databases (MEDLINE, EMBASE, SCOPUS, CINAHL and AMED) and reference checking methods were used to identify all relevant English articles that considered MetS and RCRSP. Studies were appraised using the Newcastle Ottawa Scale (NOS). Two reviewers performed critical appraisal and data extraction. Narrative synthesis was performed via content analysis of statistically significant associations . Results Three cross-sectional, two case-control and one cohort study met the inclusion criteria, providing a total of 1,187 individuals with RCRSP. Heterogeneity in methodology and RCRSP or MetS definition precluded a meaningful meta-analysis. Four of the included studies identified associations between the prevalence of MetS and RCRSP. Studies consistently identified independent cardiometabolic risk factors associated with RCRSP. All studies were level III evidence. Summary and Conclusion The low-moderate quality evidence included in this review suggests an association between MetS and RCRSP. Most studies demonstrated moderate quality on appraisal. The direction of association and cardiometabolic factors influencing should be investigated by longitudinal and treatment studies. These preliminary conclusions and clinical utility should be treated with caution due to limitations of the evidence bas

Developmentally vitamin D-deficient rats show enhanced prepulse inhibition after acute δ9-tetrahydrocannabinol

Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, Δ-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids

Gene regulation by CcpA and catabolite repression explored by RNA-Seq in Streptococcus mutans

A bacterial transcriptome of the primary etiological agent of human dental caries, Streptococcus mutans, is described here using deep RNA sequencing. Differential expression profiles of the transcriptome in the context of carbohydrate source, and of the presence or absence of the catabolite control protein CcpA, revealed good agreement with previously-published DNA microarrays. In addition, RNA-seq considerably expanded the repertoire of DNA sequences that showed statistically-significant changes in expression as a function of the presence of CcpA and growth carbohydrate. Novel mRNAs and small RNAs were identified, some of which were differentially expressed in conditions tested in this study, suggesting that the function of the S. mutans CcpA protein and the influence of carbohydrate sources has a more substantial impact on gene regulation than previously appreciated. Likewise, the data reveal that the mechanisms underlying prioritization of carbohydrate utilization are more diverse than what is currently understood. Collectively, this study demonstrates the validity of RNA-seq as a potentially more-powerful alternative to DNA microarrays in studying gene regulation in S. mutans because of the capacity of this approach to yield a more precise landscape of transcriptomic changes in response to specific mutations and growth conditions

Cognitive performance and response inhibition in developmentally vitamin D (DVD)-deficient rats

Evidence from epidemiological studies suggest that low levels of vitamin D during early life alter brain development and may increase the risk of various adverse health outcomes, including schizophrenia. The aim of this experiment was to examine the effect of developmental vitamin D (DVD) deficiency on attentional processing using the 5-choice serial reaction time task (5C-SRT) and the 5-choice continuous performance test (5C-CPT), which specifically assesses sustained attention and vigilance in rodents. DVD-deficient and control rats were exposed to a series of target and non-target trials within each operant testing session. A number of measures were recorded including hit, miss, false alarm and correct rejection, as well as premature and perseverative responses. Performance on 5C-CPT was also assessed after administration of the atypical antipsychotic, clozapine. The adult offspring of DVD-deficient rats had higher levels of impulsivity, as demonstrated by a significant increase in premature responses. On the 5C-SRT and target trials of the 5C-CPT, accuracy was not significantly affected by prenatal diet; however DVD-deficient rats made 50% fewer correct rejections compared to controls on non-target trials of the 5C-CPT. Thus, control rats were able to discriminate between target and non-target trials, whereas DVD-deficient rats were unable to make this discrimination. Clozapine reduced the occurrence of false alarms in DVD-deficient rats to a level comparable to control values. Taken together these data suggest DVD-deficient rats have increased impulsivity as well as a lack of inhibitory control, and these features may be informative in terms of modeling the cognitive deficits observed in schizophrenia

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Phylogenomics and the dynamic genome evolution of the genus Streptococcus

The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group

Content specificity of attentional bias to threat in post-traumatic stress disorder

Background: Attentional bias to affective information and reduced cognitive control may maintain the symptoms of post-traumatic stress disorder (PTSD) and impair cognitive functioning. However, the role of content specificity of affective stimuli (e.g., trauma-related, emotional trauma-unrelated) in the observed attentional bias and cognitive control is less clear, as this has not been tested simultaneously before. Therefore, we examined the content specificity of attentional bias to threat in PTSD

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage