It is well known that tumours arising in different organs are innervated and that ‘perineural invasion’ (cancer cells escaping from the tumour by following the nerve trunk) is a negative prognostic ...factor. More surprisingly, increasing evidence suggests that the nerves can provide active inputs to tumours and there is two-way communication between nerves and cancer cells within the tumour microenvironment. Cells of the immune system also interact with the nerves and cancer cells. Thus, the nerve connections can exert significant control over cancer progression and modulating these (physically or chemically) can affect significantly the cancer process. Nerve inputs to tumours are derived mainly from the sympathetic (adrenergic) and the parasympathetic (cholinergic) systems, which are interactive. An important component of the latter is the vagus nerve, the largest of the cranial nerves. Here, we present a two-part review of the nerve inputs to tumours and their effects on tumorigenesis. First, we review briefly some relevant general issues including ultrastructural aspects, stemness, interactions between neurones and primary tumours, and communication between neurones and metastasizing tumour cells. Ultrastructural characteristics include synaptic vesicles, tumour microtubes and gap junctions enabling formation of cellular networks. Second, we evaluate the pathophysiology of the nerve input to five major carcinomas: cancers of prostate, stomach, colon, lung and pancreas. For each cancer, we present (i) the nerve inputs normally present in the cancer organ and (ii) how these interact and influence the cancer process. The best clinical evidence for the role of nerves in promoting tumorigenesis comes from prostate cancer patients where metastatic progression has been shown to be suppressed significantly in cases of spinal cord injury. The balance of the sympathetic and parasympathetic contributions to early versus late tumorigenesis varies amongst the different cancers. Different branches of the vagus provide functional inputs to several of the carcinomas and, in two-way interaction with the sympathetic nervous system, affect different stages of the cancer process. Overall, the impact of the vagus nerve can be ‘direct’ or ‘indirect’. Directly, the effect of the vagus is primarily to promote tumorigenesis and this is mediated through cholinergic receptor mechanisms. Indirectly, pro- and anti-tumour effects can occur by stimulation or inhibition of the sympathetic nervous system, respectively. Less well understood are the ‘indirect’ anti-tumour effect of the vagus nerve via immunomodulation/inflammation, and the role of sensory innervation. A frequent occurrence in the nerve-tumour interactions is the presence of positive feedback driven by agents like nerve growth factor. We conclude that the nerve inputs to tumours can actively and dynamically impact upon cancer progression and are open to clinical exploitation.
In 2015, the Nordic countries (Sweden, Denmark, Finland, Norway and Iceland) initiated a project to help strengthen the efforts of conservation and use of crop wild relatives (CWR) across the region. ...Policy recommendations that were put forward included creating national strategies for each Nordic country and adopting and implementing complementary in situ conservation as the main approach for safeguarding CWR across the region. The present work explores in greater detail the situation for Sweden. Taxa rich areas and areas where potential data bias may be prevalent are located. An eco-geographic map is constructed to help determine how genetic diversity may be portioned across the country within populations of taxa. An in situ complementarity analysis accounting for taxa richness, eco-geographic richness and the protected area network in the country is also presented. Possible reasons for diverging results, as compared to the regional analysis, are discussed. The document serves as a starting point for further in-depth research on CWR distribution, conservation and use within Sweden.
Indonesia is a global hotspot of plant diversity. The country contains medicinal plants that have immense value to the people and worldwide. However, climate change is affecting the distribution of ...medicinal plants in Indonesia. In this study, the future greenhouse gas emission scenarios of RCP4.5 and RCP8.5 for a mid-term future projection to 2050 and a long-term future projection to 2080 were used to simulate the effect of climate change upon medicinal plants distribution within Indonesia. In 2050 and 2080, under both RCP scenarios species richness is expected to decrease over more than half the current distribution area of medicinal plant species. Over half of the medicinal plant species populations will lose up to 80% of their distribution area. Medicinal plant species on the islands of Papua, Java, and Sulawesi are predicted to have the largest reduction in distribution area. In addition, two-thirds of species will lose rather than gain areas of suitable climate under the future climate scenarios. Twenty medicinal plant species are identified as potentially being the most threatened by climate change in the future and are therefore the highest priority for conservation actions within Indonesia. Using these results, we recommend areas and species suitable for long term in situ and ex situ conservation within Indonesia.
We support the notion that the neural connections of the tumor microenvironment (TME) and the associated 'bioelectricity' play significant role in the pathophysiology of cancer. In several cancers, ...the nerve input promotes the cancer process. While straightforward surgical denervation of tumors, therefore, could improve prognosis, resulting side effects of such a procedure would be unpredictable and irreversible. On the other hand, tumor innervation can be manipulated effectively for therapeutic purposes by alternative novel approaches broadly termed "electroceuticals." In this perspective, we evaluate the clinical potential of targeting the TME first through manipulation of the nerve input itself and second by application of electric fields directly to the tumor. The former encompasses several different biophysical and biochemical approaches. These include implantable devices, nanoparticles, and electroactive polymers, as well as optogenetics and chemogenetics. As regard bioelectrical manipulation of the tumor itself, the "tumor-treating field" technique, applied to gliomas commonly in combination with chemotherapy, is evaluated. Also, as electroceuticals, drugs acting on ion channels and neurotransmitter receptors are highlighted for completeness. It is concluded, first, that electroceuticals comprise a broad range of biomedical tools. Second, such electroceuticals present significant clinical potential for exploiting the neural component of the TME as a strategy against cancer. Finally, the inherent bioelectric characteristics of tumors themselves are also amenable to complementary approaches. Collectively, these represent an evolving, dynamic field and further progress and applications can be expected to follow both conceptually and technically.
To investigate the underlying mechanisms of postoperative cognitive dysfunction and the impairment of medial prefrontal cortex-hippocampus connectivity. Postoperative cognitive dysfunction frequently ...affects elderly following surgery. The role of inter-brain-region connectivity abnormality after anesthesia and surgery on postoperative cognitive dysfunction development remains unclear. Medial prefrontal cortex-hippocampus connectivity of aged and adult rats was evaluated by injecting neurotracer biotinylated dextranamine (BDA) into bilateral hippocampus 3 days before partial hepatectomy, and biotinylated dextranamine positive cells of medial prefrontal cortex 2 days after hepatectomy were counted. HDAC6 shRNA was injected into medial prefrontal cortex and hippocampus bilaterally before hepatectomy or an HDAC6 activity inhibitor Tubastatin A was administered systemically after hepatectomy. Neuroinflammation and HDAC6 down-target ac-tubulin in medial prefrontal cortex and hippocampus were detected. Learning and memory of rats were evaluated by Barnes Maze task during 2–5 days after surgery and delayed matching-to-place water maze task during 10–23 days after surgery. Compared to the age-matched normal controls, anesthesia and surgery significantly decreased BDA-positive neurons in medial prefrontal cortex of aged rats, but not young adult rats. Local HDAC6 knockdown and systemic HDAC6 inhibition both increased BDA-positive neurons number of medial prefrontal cortex, alleviated learning and memory impairment in the Barnes Maze task and water maze task, decreased HDAC6 expression, inflammatory cytokines, astrocyte and microglial activation, and increased ac-tubulin expression in aged rats which received surgery. Our data indicated that anesthesia and surgery impaired medial prefrontal cortex-hippocampus connectivity and cognition which was associated with HDAC6 overexpression.
Aim: To contribute directly to Norway's national and international commitments to systematic, long-term conservation of crop wild relatives (CWR) by ensuring both the in situ and ex situ protection ...and availability of a broad range of CWR genetic diversity within the country. Location: Norway. Methods: We created a priority list of CWR within Norway based upon four main criteria including economic value from national to global level of associated crops and inclusion in Annex 1 of the International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA). Species presence data were gathered from the Global Biodiversity Information Facility (GBIF) and used for predictive species distribution modelling in MaxEnt. CAPFITOGEN software was utilized to create an ecogeographic land characterization (ELC) map and to identify complementary in situ genetic reserves and ex situ collecting priorities which target the full range of ecogeographic diversity of taxa. Results: An inventory of 204 priority CWR within Norway was compiled. A grid cell complementary network of 19 in situ areas (~10 km²) conserved 201 priority CWR, and a separate analysis identified a protected area complementary network of 23 reserves that conserved 181 priority taxa. For ex situ conservation, 177 taxa did not have ex situ accessions and of the 24 with accessions, 15 had the minimum of five populations conserved throughout their ecogeographic range. Main conclusions: We present the first comprehensive national recommendations for in situ and ex situ conservation of 204 priority CWR in Norway. Proposals target the conservation of the ecogeographic diversity of the priority CWR and hence their genetic diversity. Both the priority taxa and the methodology used are applicable at regional and global scales with the recommendations not only helping Norway to meet its international obligations for conservation of genetic diversity of CWR but also ensuring this genetic diversity is available for use in tackling global food security.
Conservation programmes are always limited by available resources. Careful planning is therefore required to increase the efficiency of conservation and gap analysis can be used for this purpose. ...This method was used to assess the representativeness of current ex situ and in situ conservation actions of 234 priority crop wild relatives (CWR) in Indonesia. This analysis also included species distribution modelling, the creation of an ecogeographical land characterization map, and a complementarity analysis to identify priorities area for in situ conservation and for further collecting of ex situ conservation programmes. The results show that both current ex situ and in situ conservation actions are insufficient. Sixty-six percent of priority CWRs have no recorded ex situ collections. Eighty CWRs with ex situ collections are still under-represented in the national genebanks and 65 CWRs have no presence records within the existing protected area network although 60 are predicted to exist in several protected areas according to their potential distribution models. The complementarity analysis shows that a minimum of 61 complementary grid areas (complementary based on grid cells) are required to conserve all priority taxa and 40 complementary protected areas (complementary based on existing protected areas) are required to conserve those with known populations within the existing in situ protected area network. The top ten of complementary protected areas are proposed as the initial areas for the development of CWR genetic reserves network in Indonesia. It is recommended to enhanced coordination between ex situ and in situ conservation stakeholders for sustaining the long term conservation of CWR in Indonesia. Implementation of the research recommendations will provide for the first time an effective conservation planning of Indonesia’s CWR diversity and will significantly enhance the country’s food and nutritional security.
Climate change is likely to be one of the most important factors affecting our future food security. To mitigate negative impacts, we will require our crops to be more genetically diverse. Such ...diversity is available in crop wild relatives (CWRs), the wild taxa relatively closely related to crops and from which diverse traits can be transferred to the crop. Conservation of such genetic resources resides within the nation where they are found; therefore, national-level conservation recommendations are fundamental to global food security. We investigate the potential impact of climate change on CWR richness in Norway. The consequences of a 1.5 and 3.0 °C temperature rise were studied for the years 2030, 2050, 2070, 2080 and then compared to the present climate. The results indicate a pattern of shifting CWR richness from the south to the north, with increases in taxa turnover and in the numbers of threatened taxa. Recommendations for in situ and ex situ conservation actions over the short and long term for the priority CWRs in Norway are presented. The methods and recommendations developed here can be applied within other nations and at regional and global levels to improve the effectiveness of conservation actions and help ensure global food security.
Growing research interest in crop wild relatives (CWR) has highlighted their value for crop improvement, particularly to mitigate the impact of climate change and contribute to global food security. ...As most conservation activities are implemented at national level there is a requirement for each country to develop and implement a national CWR conservation strategy. This will contribute to regional and global CWR conservation actions and so help achieve CBD Aichi Targets 13 of improved genetic conservation of socio-economically important taxa. Cyprus has historically lacked systematic CWR conservation but is rich in CWR diversity being located in the eastern Mediterranean Vavilov centre and abutting the Fertile Crescent. Therefore a more coherent approach to CWR conservation is desirable. From an initial checklist of 1,722 Cypriot CWR taxa, 178 CWR were prioritized and eco geographic data was collated and analysed using GIS techniques. The Troodos and Pafos mountains are CWR hotspots and ten priority sites containing the genetic diversity of 74.7 % of priority CWR taxa were identified. These will form the basis of a national network of in situ genetic reserves and 78 priority CWR taxa that have no accessions in the national Cyprus gene bank are highlighted for collection and ex situ storage.
Climate change and anthropogenic activities threaten our global food security. One area of research that may help combat a future food crisis is the utilization of the genetic diversity available in ...wild plants. Crop wild relatives (CWR) are one such resource. They are the wild taxa most closely related to crops and from which diverse traits could be transferred to the crop. This project uses Norway as an example, to contribute towards methodologies to identify those CWR populations that are most important for conservation and use. This involves the creation of a priority list of CWR for Norway, in situ and ex situ diversity analysis of CWR populations, gap analysis and ecogeographic land characterization methodologies, predictive climate change analysis for CWR distributions and genetic diversity studies of taxa using Amplified Fragment Length Polymorphisms (AFLPs). Comprehensive in situ and ex situ national recommendations for the conservation of CWR in Norway are detailed. These include the incorporation of management plans for CWR populations within the Færder national park in Norway, the first instance of such conservation activities in Scandinavia. The scientific methods used and developed will help Norway meet its international obligations for conservation and use of genetic diversity of CWR and will contribute to the regional and global efforts to systematically conserve and utilize the diversity found in CWR.
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