Deep sequencing of Suppression Subtractive Hybridisation drought and recovery libraries of the non-model crop Trifolium repens L.

Open Access Journal; Published online: 23 Feb. 2017White clover is a short-lived perennial whose persistence is greatly affected by abiotic stresses, particularly drought. The aim of this work was to characterize its molecular response to water deficit and recovery following re-hydration to identify targets for the breeding of tolerant varieties. We created a white clover reference transcriptome of 16,193 contigs by deep sequencing (mean base coverage 387x) four Suppression Subtractive Hybridization (SSH) libraries (a forward and a reverse library for each treatment) constructed from young leaf tissue of white clover at the onset of the response to drought and recovery. Reads from individual libraries were then mapped to the reference transcriptome and processed comparing expression level data. The pipeline generated four robust sets of transcripts induced and repressed in the leaves of plants subjected to water deficit stress (6,937 and 3,142, respectively) and following re-hydration (6,695 and 4,897, respectively). Semi-quantitative polymerase chain reaction was used to verify the expression pattern of 16 genes. The differentially expressed transcripts were functionally annotated and mapped to biological processes and pathways. In agreement with similar studies in other crops, the majority of transcripts up-regulated in response to drought belonged to metabolic processes, such as amino acid, carbohydrate, and lipid metabolism, while transcripts involved in photosynthesis, such as components of the photosystem and the biosynthesis of photosynthetic pigments, were up-regulated during recovery. The data also highlighted the role of raffinose family oligosaccharides (RFOs) and the possible delayed response of the flavonoid pathways in the initial response of white clover to water withdrawal. The work presented in this paper is to our knowledge the first large scale molecular analysis of the white clover response to drought stress and re-hydration. The data generated provide a valuable genomic resource for marker discovery and ultimately for the improvement of white clover

The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety

Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARγ) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were randomized to either active (45 mg, n = 14) or placebo (0 mg, n = 16) PIO maintenance for the duration of the three-week study. After stabilization on buprenorphine (8 mg), participants began a two-week testing period. On the first to fourth test days, participants could self-administer drug or money by making verbal choices for either option. On the fifth day, active heroin and money were administered and participants could work to receive heroin or money using a progressive ratio choice procedure. Test days 6–10 were identical to test days 1–5 with the exception that, during one of the test weeks, placebo was available on the first four days, and during the other week heroin was available. PIO failed to alter the reinforcing or positive subjective effects of heroin, but it did reduce heroin craving and overall anxiety. Although we were unable to replicate the robust effects found in preclinical models, these data provide an indication of drug effects that deserves further exploration

Scalable off-grid energy services enabled by IoT: A case study of BBOXX SMART Solar

This case study intends to show how Internet of Things (IoT) technology can be used to tackle development challenges by using the case study of BBOXX- a Solar Home Systems provider operating in South-Western Kenya and across Rwanda, and its SMART Solar platform applied to nearly 20,000 currently active systems. It aims to highlight the benefits of such technology to its users and how it can be utilised to create scalable business models for energy access through improved customer understanding. However, it also shows the difficulties in designing, developing and deploying appropriate technologies in an affordable and impactful way. Similar applications in the water sector are briefly looked at to further explore the potential and the challenges of IoT technologies in driving social and economic development. The case study raises ethical questions about the storage, collection and sharing of data and explores whether the data protection models prevalent in the developed world are applicable in a development context. It offers ideas for future research and policy recommendations, pointing to the need of including financial, socio-economic and ethical considerations in the processes of innovative solutions development

Memantine reduces consumption of highly palatable food in a rat model of binge eating

Excessive consumption of highly palatable food has been linked to the development of eating disorders and obesity, and can be modeled in non-food-deprived rats by offering them a limited (2-h daily) access to an optional dietary fat. Since the glutamatergic system has recently emerged as a viable target for binge-eating medication development, we compared the effects of subchronic treatment with glutamatergic receptor antagonists to the effects of a reference appetite-suppressing agent sibutramine on highly palatable food (lard) and normal chow intake. In three separate experiments, the consumption of a standard laboratory chow and lard were measured during 12 days of medication treatment and for 6 days afterwards. Generalized estimating equations analysis demonstrated that sibutramine (7.5 mg/kg, PO) significantly decreased lard consumption, with a concurrent increase in chow consumption. Sibutramine effects disappeared after treatment discontinuation. The NMDA receptor antagonist memantine (5 mg/kg, IP) significantly decreased lard consumption and increased chow consumption, comparable to effects of sibutramine; however, memantine’s effects persisted after treatment discontinuation. The effects of the mGluR5 antagonist MTEP (7.5 mg/kg, IP) on food consumption were in the same direction as seen with memantine, but the observed differences were not significant. In an additional control experiment, sibutramine and memantine reduced unlimited (24 h) chow intake during the treatment phase. Present results provide evidence that glutamatergic neurotransmission might be involved in the regulation of excessive consumption of highly palatable foods, and suggest that NMDA receptor may be an attractive target for developing obesity and disordered eating pharmacotherapies

COVID-19 Features in Patients with Multiple Sclerosis: Main Approaches to Their Management, Treatment, and Vaccination

The COVID-19 pandemic calls for correct and evidence-based decisions regarding management and treatment of patients with multiple sclerosis. Information on researches, clinical cases, and recommendations for treatment of such patients during the pandemic should be classified. We report COVID-19 features in patients with multiple sclerosis, risk factors for infection and development of severe disease. We also describe management strategies for multiple sclerosis: from relapse treatment to the selection of disease-modifying therapies focusing on patients safety. We analyze the latest observational and comparative studies, clinical cases of multiple sclerosis patients vaccination and demyelinating disease onset after COVID-19 or vaccination

СОВЕРШЕНСТВОВАНИЕ ОБСЛЕДОВАНИЯ ЗРИТЕЛЬНОГО АНАЛИЗАТОРА ПРИ РАССЕЯННОМ СКЛЕРОЗЕ

137 (274 eyes) relapsing-remitting multiple sclerosis patients have been given detailed neuroophthalmologic examination. 58 of these patients (74 eyes) had a previous history of optic neuritis. As a result, the most informative methods of examination have been identified. These include the estimation of the frequency characteristics of the vision (vizokontrastoperimetriya, low-contrast tests Sloan), standard static automated perimetry, pattern visual evoked potentials, and optical coherence tomography which is used to measure macular volumes and retinal nerve fiber layer thickness. The above – mentioned methods make it possible to reveal the involvement of the optic analyzer in the inflammatory and neurodegenerative process at the pre-clinical stage. The obtained results allow us to recommend inclusion of the methods in the standard algorithm for the examination of patients with probable multiple sclerosis. Проведено детальное нейроофтальмологическое обследование 137 пациентов с рецидивирующеремиттирующей формой рассеянного склероза (274 глаза). Из них 58 пациентов (74 глаза) имели в анамнезе оптический неврит. Были определены наиболее информативные методы обследования, позволяющие еще на доклинической стадии выявить вовлечение зрительного анализатора в воспалительный и нейродегенеративный процессы: оценка частотных характеристик органа зрения (визоконтрастопериметрия, низкоконтрастные таблицы Слоан), статическая автоматизированная периметрия, зрительные вызванные потенциалы на шахматный паттерн, оптическая когерентная томография для определения толщины слоя нервных волокон сетчатки. Полученные результаты позволяют рекомендовать их включение в стандартный алгоритм обследования больных с вероятным рассеянным склерозом.

Mapping synergies and trade-offs between energy and the Sustainable Development Goals

The 2030 Agenda for Sustainable Development—including 17 interconnected Sustainable Development Goals (SDGs) and 169 targets—is a global plan of action for people, planet and prosperity. SDG7 calls for action to ensure access to affordable, reliable, sustainable and modern energy for all. Here we characterize synergies and trade-offs between efforts to achieve SDG7 and delivery of the 2030 Agenda as a whole. We identify 113 targets requiring actions to change energy systems, and published evidence of relationships between 143 targets (143 synergies, 65 trade-offs) and efforts to achieve SDG7. Synergies and trade-offs exist in three key domains, where decisions about SDG7 affect humanity’s ability to: realize aspirations of greater welfare and well-being; build physical and social infrastructures for sustainable development; and achieve sustainable management of the natural environment. There is an urgent need to better organize, connect and extend this evidence, to help all actors work together to achieve sustainable development. On 5 September 2015, the 193 members states of the United Nations (UN) adopted a new 2030 Agenda for Sustainable Development. The 2030 Agenda succeeds the UN’s Millennium Development Goals (MDGs), and features 17 Sustainable Development Goals (SDGs) with 169 targets, which UN member states have committed to implement by 2030. Energy was not explicitly referred to in the MDGs, and came to be referred to as the ‘missing’ MDG. During the operational period of the MDGs and negotiation of the 2030 Agenda, it was increasingly recognized that energy underpins economic and social development, without which it would not be possible to eliminate poverty. This change in status made sustainable energy provision and access one of the central themes of the 2030 Agenda, whose preamble calls for “universal access to affordable, reliable and sustainable energy” and recognizes that “social and economic development depends of the sustainable management of our planet’s natural resources”. SDG7 is accompanied by five targets to be achieved by 2030: ensure universal access to affordable, reliable and modern energy services (7.1); increase the share of renewable energy in the global energy mix (7.2); double the global rate of improvement in energy efficiency (7.3); enhance international cooperation to facilitate access to clean energy research and technology (7.a), and promote investment in energy infrastructure and clean energy technology (7.b). By understanding the complex links between the SDGs and their constituent targets, researchers can better support policymakers to think systematically about interactions between the different SDGs, including how actions to achieve each goal affect each other within and between sectors. Studies to date have lacked a target-level approach or have focussed on only a few of the SDGs. Here we present a formative attempt by an interdisciplinary group of researchers to identify the full range of goals and targets in the 2030 Agenda that call for changes in energy systems, and characterize evidence of synergies or trade-offs between delivery of each of the 169 targets and efforts focussed on pursuit of SDG7 and each of its constituent targets. The purpose of this Perspective is not to provide definitive answers. Instead we aim to lay a foundation for systematic (and context-specific) exploration of the interlinkages between each of the SDG targets, in the context of decision-making about development and the transformation of energy systems

Memantine increases NMDA receptor level in the prefrontal cortex but fails to reverse apomorphine-induced conditioned place preference in rats

Studies have shown that inflammation and neurodegeneration may accompany the development of addiction to apomorphine and that the glutamate NMDA receptor antagonist, memantine, may be neuroprotective. The similarity between apomorphine and dopamine with regard to their chemical, pharmacological and toxicological properties provided a basis for investigating the mechanism of action of the former agent. In this study, we investigated whether memantine would suppress apomorphine-seeking behavior in rats subjected to apomorphine-induced place preference conditioning, through modulation of NMDA receptors in the prefrontal cortex. Repeated apomorphine (1 mg/kg) treatment induced conditioned place preference (CPP) and had no significant effect on NMDA receptor levels in the prefrontal cortex. Prior treatment with memantine (5 mg/kg or 10 mg/kg) increased the levels of NMDA receptors in the prefrontal cortex but did not suppress CPP induced by apomorphine. These data give further support to the addictive effect of apomorphine and demonstrate that blockade of NMDA receptors by memantine is unable to suppress apomorphine-seeking behavior

Operant Sensation Seeking Requires Metabotropic Glutamate Receptor 5 (mGluR5)

Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior