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

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’

Space Weather in the Saturn-Titan System

New evidence based on Cassini magnetic field and plasma data has revealed that the discovery of Titan outside Saturn’s magnetosphere during the T96 flyby on 2013 December 1 was the result of the impact of two consecutive interplanetary coronal mass ejections (ICMEs) that left the Sun in 2013 early November and interacted with the moon and the planet. We study the dynamic evolution of Saturn's magnetopause and bow shock, which evidences a magnetospheric compression from late November 28 to December 4 (at least), under prevailing solar wind dynamic pressures of 0.16-0.3 nPa. During this interval, transient disturbances associated with the two ICMEs are observed, allowing for the identification of their magnetic structures. By analyzing the magnetic field direction, and the pressure balance in Titan’s induced magnetosphere, we show that Cassini finds Saturn’s moon embedded in the second ICME after being swept by its interplanetary shock and amid a shower of solar energetic particles that may have caused dramatic changes in the moon’s lower ionosphere. Analyzing a list of Saturn's bow shock crossings during 2004-2016, we find that the magnetospheric compression needed for Titan to be in the supersonic solar wind can be generally associated with the presence of an ICME or a corotating interaction region. This leads to the conclusion that Titan would rarely face the pristine solar wind, but would rather interact with transient solar structures under extreme space weather conditions

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

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

Shocklets and Short Large Amplitude Magnetic Structures (SLAMS) in the high Mach foreshock of Venus

Shocklets and short large-amplitude magnetic structures (SLAMS) are steepened magnetic fluctuations commonly found in Earth's upstream foreshock. Here we present Venus Express observations from the 26th of February 2009 establishing their existence in the steady-state foreshock of Venus, building on a past study which found SLAMS during a substantial disturbance of the induced magnetosphere. The Venusian structures were comparable to those reported near Earth. The 2 Shocklets had magnetic compression ratios of 1.23 and 1.34 with linear polarization in the spacecraft frame. The 3 SLAMS had ratios between 3.22 and 4.03, two of which with elliptical polarization in the spacecraft frame. Statistical analysis suggests SLAMS coincide with unusually high solar wind Alfvén mach-number at Venus (12.5, this event). Thus, while we establish Shocklets and SLAMS can form in the stable Venusian foreshock, they may be rarer than at Earth. We estimate a lower limit of their occurrence rate of ≳14%

Attentional Processing in C57BL/6J Mice Exposed to Developmental Vitamin D Deficiency

Epidemiological evidence suggests that Developmental Vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT) and five-choice continuous performance test (5C-CPT), as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour

The Effects of Breeding Protocol in C57BL/6J Mice on Adult Offspring Behaviour

Animal experiments have demonstrated that a wide range of prenatal exposures can impact on the behaviour of the offspring. However, there is a lack of evidence as to whether the duration of sire exposure could affect such outcomes. We compared two widely used methods for breeding offspring for behavioural studies. The first involved housing male and female C57Bl/6J mice together for a period of time (usually 10–12 days) and checking for pregnancy by the presence of a distended abdomen (Pair-housed; PH). The second involved daily introduction of female breeders to the male homecage followed by daily checks for pregnancy by the presence of vaginal plugs (Time-mated; TM). Male and female offspring were tested at 10 weeks of age on a behavioural test battery including the elevated plus-maze, hole board, light/dark emergence, forced swim test, novelty-suppressed feeding, active avoidance and extinction, tests for nociception and for prepulse inhibition (PPI) of the acoustic startle response. We found that length of sire exposure (LSE) had no significant effects on offspring behaviour, suggesting that the two breeding protocols do not differentially affect the behavioural outcomes of interest. The absence of LSE effects on the selected variables examined does not detract from the relevance of this study. Information regarding the potential influences of breeding protocol is not only absent from the literature, but also likely to be of particular interest to researchers studying the influence of prenatal manipulations on adult behaviour

High Diversity of the Saliva Microbiome in Batwa Pygmies

We describe the saliva microbiome diversity in Batwa Pygmies, a former hunter-gatherer group from Uganda, using next-generation sequencing of partial 16S rRNA sequences. Microbial community diversity in the Batwa is significantly higher than in agricultural groups from Sierra Leone and the Democratic Republic of Congo. We found 40 microbial genera in the Batwa, which have previously not been described in the human oral cavity. The distinctive composition of the salvia microbiome of the Batwa may have been influenced by their recent different lifestyle and diet