Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII

Regulation of intracellular cyclic adenosine 3’, 5’-monophosphate (cAMP) by multiple pathways enables differential function of this ubiquitous second messenger in a context dependent manner. Modulation of Gs-stimulated intracellular cAMP has long been known to be modulated by the Gi and Gq/Ca2+ pathways. Recently, the G13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the Gs and G13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the alpha subunit of either G12 or G13. Our results demonstrate that AC7 is a specific downstream effector of the G12/13 pathway

Challenges and Solutions for Functional Neurosurgery in Developing Countries.

Functional neurosurgery techniques remain integral to the neurosurgical treatment armamentarium but data on global implementation remains scarce. In comparison to high-income countries (HIC), low- and middle-income countries (LMIC) suffer from an increased prevalence of diseases like epilepsy, which may be amenable to functional techniques, and therefore, LMIC may benefit from an increased utilization of these treatment modalities. However, functional techniques tend to be expensive and thus difficult to implement in the LMIC setting. A review was performed to assess the current status of functional neurosurgical techniques in LMIC as a starting point for future initiatives. For methodology, a review of the current body of literature on functional neurosurgery in LMIC was conducted through the United States National Library of Medicine Pubmed search engine. Search terms included "functional neurosurgery," "developing countries," "low and middle income," and other related terms. It was found that though five billion people lack access to safe surgical care, the burden of disease amenable to treatment with functional neurosurgical procedures remains unknown. Increasingly, reports of successful, long-term, international neurosurgical collaborations are being reported, but reports in the sub-field of functional neurosurgery are lacking. In conclusion, awareness of global surgical disparities has increased dramatically while global guidelines for functional techniques are currently lacking. A concerted effort can harness these techniques for wider practice. Partnerships between centers in LMIC and HIC are making progress to better understand the burden of disease in LMIC and to create context-specific solutions for practice in the LMIC setting, but more collaborations are warranted

Metabolite profiling of yam (Dioscorea spp.) accessions for use in crop improvement programmes

Article purchased; Published online: 14 Oct. 2017Introduction Ninety-seven percent of yam (Dioscorea spp.) production takes place in low income food deficit countries (LIFDCs) and the crop provides 200 calories a day to approximately 300 million people. Therefore, yams are vital for food security. Yams have high-yield potential and high market value potential yet current breeding of yam is hindered by a lack of genomic information and genetic resources. New tools are needed to modernise breeding strategies and unlock the potential of yam to improve livelihood in LIFDCs. Objectives Metabolomic screening has been undertaken on a diverse panel of Dioscorea accessions to assess the utility of the approach for advancing breeding strategies in this understudied crop. Methods Polar and lipophilic extracts from tubers of accessions from the global yam breeding program have been comprehensively profiled via gas chromatography-mass spectrometry. Results A visual pathway representation of the measured yam tuber metabolome has been delivered as a resource for biochemical evaluation of yam germplasm. Over 200 compounds were routinely measured in tubers, providing a major advance for the chemo-typing of this crop. Core biochemical redundancy concealed trends that were only elucidated following detailed mining of global metabolomics data. Combined analysis on leaf and tuber material identified a subset of metabolites which allow accurate species classification and highlighted the potential of predicting tuber composition from leaf profiles. Metabolic variation was accessionspecific and often localised to compound classes, which will aid trait-targeting for metabolite markers. Conclusions Metabolomics provides a standalone platform with potential to deliver near-future crop gains for yam. The approach compliments the genetic advancements currently underway and integration with other ‘–omics’ studies will deliver a significant advancement to yam breeding strategies

Temperature and Oxidative Stress as Triggers for Virulence Gene Expression in Pathogenic Leptospira spp.

Leptospirosis is a zooanthroponosis aetiologically caused by pathogenic bacteria belonging to the genus, Leptospira. Environmental signals such as increases in temperatures or oxidative stress can trigger response regulatory modes of virulence genes during infection. This study sought to determine the effect of temperature and oxidative stress on virulence associated genes in highly passaged Leptospira borgpeterseneii Jules and L. interrogans Portlandvere. Bacteria were grown in EMJH at 30°C, 37°C, or at 30°C before being transferred to 37°C. A total of 14 virulence-associated genes (fliY, invA, lenA, ligB, lipL32, lipL36, lipL41, lipL45, loa22, lsa21, mce, ompL1, sph2, and tlyC) were assessed using endpoint PCR. Transcriptional analyses of lenA, lipL32, lipL41, loa22, sph2 were assessed by quantitative real-time RT-PCR at the temperature conditions. To assess oxidative stress, bacteria were exposed to H2O2 for 30 and 60 min with or without the temperature stress. All genes except ligB (for Portlandvere) and ligB and mce (for Jules) were detectable in the strains. Quantitatively, temperature stress resulted in significant changes in gene expression within species or between species. Temperature changes were more influential in gene expression for Jules, particularly at 30°C and upshift conditions; at 37°C, expression levels were higher for Portlandvere. However, compared to Jules, where temperature was influential in two of five genes, temperature was an essential element in four of five genes in Portlandvere exposed to oxidative stress. At both low and high oxidative stress levels, the interplay between genetic predisposition (larger genome size) and temperature was biased towards Portlandvere particularly at 30°C and upshift conditions. While it is clear that expression of many virulence genes in highly passaged strains of Leptospira are attenuated or lost, genetic predisposition, changes in growth temperature and/or oxidative intensity and/or duration were factors which acted in isolation or together with other regulatory cues to contribute to the variable gene expression observed in this study. Overall, differential gene expression in serovar Portlandvere was more responsive to temperature and oxidative stress

Metabolite profiling characterises chemotypes of Musa diploids and triploids at juvenile and preflowering growth stages

Open Access Journal; Published online: 15 March 2019Bananas (Musa spp.) are consumed worldwide as dessert and cooking types. Edible banana varieties are for the most part seedless and sterile and therefore vegetatively propagated. This confers difficulties for breeding approaches against pressing biotic and abiotic threats and for the nutritional enhancement of banana pulp. A panel of banana accessions, representative of the diversity of wild and cultivated bananas, was analysed to assess the range of chemotypes available globally. The focus of this assessment was banana leaves at two growth stages (juvenile and pre-flowering), to see when during the plant growth metabolic differences can be established. The metabolic data corresponded to genomic trends reported in previous studies and demonstrated a link between metabolites/pathways and the genomes of M. acuminata and M. balbisiana. Furthermore, the vigour and resistance traits of M. balbisiana was connected to the phenolic composition and showed differences with the number of B genes in the hybrid accessions. Differences in the juvenile and pre-flowering data led to low correlation between the growth stages for prediction purposes