Heteromerization Modulates mu Opioid Receptor Functional Properties in vivo.

Mu opioid receptors modulate a large number of physiological functions. They are in particular involved in the control of pain perception and reward properties. They are also the primary molecular target of opioid drugs and mediate their beneficial analgesic effects, euphoric properties as well as negative side effects such as tolerance and physical dependence. Importantly, mu opioid receptors can physically associate with another receptor to form a novel entity called heteromer that exhibits specific ligand binding, signaling, and trafficking properties. As reviewed here, in vivo physical proximity has now been evidenced for several receptor pairs, subsequent impact of heteromerization on native mu opioid receptor signaling and trafficking identified and a link to behavioral changes established. Selective targeting of heteromers as a tool to modulate mu opioid receptor activity is therefore attracting growing interest and raises hopes for innovative therapeutic strategies.journal articlereview20182018 11 13importe

Developing national obesity policy in middle-income countries: a case study from North Africa

Background The prevalence of overweight and obesity is a rapidly growing threat to public health in both Morocco and Tunisia, where it is reaching similar proportions to high-income countries. Despite this, a national strategy for obesity does not exist in either country. The aim of this study was to explore the views of key stakeholders towards a range of policies to prevent obesity, and thus guide policy makers in their decision making on a national level. Methods Using Multicriteria Mapping, data were gathered from 82 stakeholders (from 33 categories in Morocco and 36 in Tunisia) who appraised 12 obesity policy options by reference to criteria of their own choosing. Results The feasibility of policies in practical or political terms and their cost were perceived as more important than how effective they would be in reducing obesity. There was most consensus and preference for options targeting individuals through health education, compared with options that aimed at changing the environment, i.e. modifying food supply and demand (providing healthier menus/changing food composition/food sold in schools); controlling information (advertising controls/mandatory labelling) or improving access to physical activity. In Tunisia, there was almost universal consensus that at least some environmental-level options are required, but in Morocco, participants highlighted the need to raise awareness within the population and policy makers that obesity is a public health problem, accompanied by improving literacy before such measures would be accepted. Conclusion Whilst there is broad interest in a range of policy options, those measures targeting behaviour change through education were most valued. The different socioeconomic, political and cultural contexts of countries need to be accounted for when prioritizing obesity policy. Obesity was not recognized as a major public health priority; therefore, convincing policy makers about the need to prioritize action to prevent obesity, particularly in Morocco, will be a crucial first step

Low Concentrations of Vitamin C Reduce the Synthesis of Extracellular Polymers and Destabilize Bacterial Biofilms

Extracellular polymeric substances (EPS) produced by bacteria form a matrix supporting the complex three-dimensional architecture of biofilms. This EPS matrix is primarily composed of polysaccharides, proteins and extracellular DNA. In addition to supporting the community structure, the EPS matrix protects bacterial biofilms from the environment. Specifically, it shields the bacterial cells inside the biofilm, by preventing antimicrobial agents from getting in contact with them, thereby reducing their killing effect. New strategies for disrupting the formation of the EPS matrix can therefore lead to a more efficient use of existing antimicrobials. Here we examined the mechanism of the known effect of vitamin C (sodium ascorbate) on enhancing the activity of various antibacterial agents. Our quantitative proteomics analysis shows that non-lethal concentrations of vitamin C inhibit bacterial quorum sensing and other regulatory mechanisms underpinning biofilm development. As a result, the EPS biosynthesis in reduced, and especially the polysaccharide component of the matrix is depleted. Once the EPS content is reduced beyond a critical point, bacterial cells get fully exposed to the medium. At this stage, the cells are more susceptible to killing, either by vitamin C-induced oxidative stress as reported here, or by other antimicrobials or treatments

INTERET DU DOSAGE DU NT- PROBNP DANS LE DIAGNOSTIC DIFFERENTIEL D’UNE DYSPNEE AIGUE AU SERVICE DES

Objective: the N-terminal fraction of the precursor of the natriuretic peptide of type B (NT-proBNP) is a marker of cardiac failure. In this work we evaluated the performances as regards diagnosis of a dyspnea which this marker can bring to the urgentists of our formation in order to direct in an adequate way the patients dyspneic, towards the various services of the Military hospital of Instruction Mohammed V Rabat. Material and method: our study was carried out among 40 patients dealt with by the team of the service of the urgencies of the Military hospital of Instruction Mohammed V for nontraumatic acute dyspnea accompanied or not by thoracic pain. The Middle Age of the studied population is 54 years with the extreme ones going from 30 to 78 years. The patients were studied on the clinical level by the medical antecedents; risk factors cardiovascular and on the biological level by the ionogramme, the NFS, gases of blood and the proportioning of the NT-proBNP. Results: the patients are classified in three groups: On the one hand according to the rate of NT-proBNP. 27 patients presented values of NT-proBNP > 1200 pg/ml, but it was not retained that 23 patients because the 4 others had been excluded because of the impaired renal function. The clinical and radiological diagnosis was obvious among 17 patients is 74%. Among 6 other patients (26%), the rate of high NT-proBNP justified the orientation of these patients in cardiology for additional investigations. The diagnoses retained by the cardiologists confirmed the cardiac presence of pathology among these patients. As for the patients whose rate of NT-proBNP lies between 250 and 1200 pg/ml (N = 3), their orientation took account of the clinical context. 10 patients presented values of NT-proBNP 1200 pg/ml, mais on n’a retenu que 23 patients car les 4 autres avaient été exclus à cause de l’insuffisance rénale. Le diagnostic clinique et radiologique était évident chez 17 patients soit 74%. Chez les 6 autres patients (26%), le taux de NT-proBNP élevé a justifié l’orientation de ces patients en cardiologie pour des investigations supplémentaires. Les diagnostics retenus par les cardiologues confirmaient la présence de pathologie cardiaque chez ces malades. Quant aux patients dont le taux de NT-proBNP est compris entre 250 et 1200 pg/ml (n = 3), leur orientation a tenu compte du contexte clinique. 10 patients présentaient des valeurs de NT-proBNP < 250 pg/ml. Aucun événement cardiaque n’a été décelé par les examens complémentaires réalisés à posteriori. D’autre part, en fonction des données clinique et paraclinique le médecin urgentiste a orienté 16 patients en pneumologie 19 patients en cardiologie 5 patients en néphrologie et réanimation. Conclusion : le NT-proBNP est d’une fiabilité manifeste par rapport aux données cliniques et paracliniques, permettant non seulement une prise en charge rapide des patients mais aussi d’éviter la prescription de bilans non justifiés  parfois très coûteux et une prolongation de la durée d’hospitalisation du malade

Comparative genomics study reveals Red Sea Bacillus with characteristics associated with potential microbial cell factories (MCFs)

© 2019, The Author(s). Recent advancements in the use of microbial cells for scalable production of industrial enzymes encourage exploring new environments for efficient microbial cell factories (MCFs). Here, through a comparison study, ten newly sequenced Bacillus species, isolated from the Rabigh Harbor Lagoon on the Red Sea shoreline, were evaluated for their potential use as MCFs. Phylogenetic analysis of 40 representative genomes with phylogenetic relevance, including the ten Red Sea species, showed that the Red Sea species come from several colonization events and are not the result of a single colonization followed by speciation. Moreover, clustering reactions in reconstruct metabolic networks of these Bacillus species revealed that three metabolic clades do not fit the phylogenetic tree, a sign of convergent evolution of the metabolism of these species in response to special environmental adaptation. We further showed Red Sea strains Bacillus paralicheniformis (Bac48) and B. halosaccharovorans (Bac94) had twice as much secreted proteins than the model strain B. subtilis 168. Also, Bac94 was enriched with genes associated with the Tat and Sec protein secretion system and Bac48 has a hybrid PKS/NRPS cluster that is part of a horizontally transferred genomic region. These properties collectively hint towards the potential use of Red Sea Bacillus as efficient protein secreting microbial hosts, and that this characteristic of these strains may be a consequence of the unique ecological features of the isolation environment

Aspects of astrocyte energy metabolism, amino acid neurotransmitter homoeostasis and metabolic compartmentation

Astrocytes are key players in brain function; they are intimately involved in neuronal signalling processes and their metabolism is tightly coupled to that of neurons. In the present review, we will be concerned with a discussion of aspects of astrocyte metabolism, including energy-generating pathways and amino acid homoeostasis. A discussion of the impact that uptake of neurotransmitter glutamate may have on these pathways is included along with a section on metabolic compartmentation

Glutamine synthetase gene expression during the regeneration of the annelid Enchytraeus japonensis

Enchytraeus japonensis is a highly regenerative oligochaete annelid that can regenerate a complete individual from a small body fragment in 4–5 days. In our previous study, we performed complementary deoxyribonucleic acid subtraction cloning to isolate genes that are upregulated during E. japonensis regeneration and identified glutamine synthetase (gs) as one of the most abundantly expressed genes during this process. In the present study, we show that the full-length sequence of E. japonensis glutamine synthetase (EjGS), which is the first reported annelid glutamine synthetase, is highly similar to other known class II glutamine synthetases. EjGS shows a 61–71% overall amino acid sequence identity with its counterparts in various other animal species, including Drosophila and mouse. We performed detailed expression analysis by in situ hybridization and reveal that strong gs expression occurs in the blastemal regions of regenerating E. japonensis soon after amputation. gs expression was detectable at the cell layer covering the wound and was found to persist in the epidermal cells during the formation and elongation of the blastema. Furthermore, in the elongated blastema, gs expression was detectable also in the presumptive regions of the brain, ventral nerve cord, and stomodeum. In the fully formed intact head, gs expression was also evident in the prostomium, brain, the anterior end of the ventral nerve cord, the epithelium of buccal and pharyngeal cavities, the pharyngeal pad, and in the esophageal appendages. In intact E. japonensis tails, gs expression was found in the growth zone in actively growing worms but not in full-grown individuals. In the nonblastemal regions of regenerating fragments and in intact worms, gs expression was also detected in the nephridia, chloragocytes, gut epithelium, epidermis, spermatids, and oocytes. These results suggest that EjGS may play roles in regeneration, nerve function, cell proliferation, nitrogenous waste excretion, macromolecule synthesis, and gametogenesis