Untranslated yet indispensable - UTRs act as key regulators in the environmental control of gene expression

To survive and thrive in a dynamic environment, plants must continuously monitor their surroundings and adjust their development and physiology accordingly. Changes in gene expression underlie these developmental and physiological adjustments and are traditionally attributed to widespread transcriptional reprogramming. Growing evidence, however, suggests that post-transcriptional mechanisms also play a vital role in tailoring gene expression to a plant's environment. Untranslated regions (UTRs) act as regulatory hubs for post-transcriptional control, harbouring cis elements that affect an mRNA's processing, localisation, translation and stability and thereby tune the abundance of the encoded protein. Here, we review recent advances made in understanding the critical function UTRs exert in the post-transcriptional control of gene expression in the context of a plant's abiotic environment. We summarise the molecular mechanisms at play, present examples of UTR-controlled signalling cascades and discuss the potential that resides within UTRs to render plants more resilient to a changing climate.</p

Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis

BACKGROUND Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. METHODS 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, Mϕ). In vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry. RESULTS In vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in Mϕ/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with Mϕ indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p &lt; 0.001) and LV (p = 0.004). CONCLUSIONS The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN

Industry perceptions of barriers to commercialization of regenerative medicine products in the UK

Aims Regenerative medicine is an emerging field with the potential to provide widespread improvement in healthcare and patient well-being via the delivery of therapies which can restore, regenerate or repair damaged tissue. As an industry, it could significantly contribute to economic growth if products are successfully commercialized. However, to date, relatively few products have reached the market due to a variety of barriers, including a lack of funding and regulatory hurdles. The present study analyzes industry perceptions of the barriers to commercialization which currently impede the success of the regenerative medicine industry in the UK. Materials & Methods The analysis is based on twenty interviews with leading industrialists in the field. Results The study revealed that scientific research on regenerative medicine is thriving in the UK. Unfortunately, lack of access to capital, regulatory hurdles, lack of clinical evidence leading to problems with reimbursement, as well as the culture of the NHS do not provide a good environment for the commercialization of RM products. Conclusions Policy interventions, including increased translational government funding, a change in NHS and NICE organisation and policies as well regulatory clarity would likely improve the general outcomes for the regenerative medicine industry in the UK

An update on the mosquito species composition and diversity in western and North Western Uganda

Although the west and north western parts of Uganda are historically known homes to a number of mosquito species and arboviruses associated with morbidity and mortality, early studies were highly focal and limited to specific collection methods. We aimed to update mosquito species composition in areas where a febrile illness study had shown evidence of arboviruses circulating. Adult mosquito sampling was done outside and inside houses using light traps baited with solid carbon dioxide and pyrethrum spray respectively. All collected mosquitoes were identified using appropriate morphological identification keys. A total of 22,455 mosquitoes from 89 species, 22 sub species and 11 genera were collected from Arua and Kasese districts. Overall abundance was found to be higher in Kasese (n=13446, 59.9%) than Arua district (n = 9009, 40.1%), though no significant differences were observed across villages in Arua and Kasese districts (Kruskal Wallis, X2 = 2, df = 3, p&gt;0.05). Collection numbers were highest for genus Coquillettidia (n = 7942, 35.4%), followed by Culex (n = 7642, 34.03%), Mansonia (n = 3414, 15.2%), Anopheles (n = 1970, 8.8%) and Aedes (n = 1349, 6.01%). Other species were across 6 genera Eretmopodites (n = 59, 0.26%), Uranoteania (n = 36, 0.16%), Lutzia (n = 26, 0.12%), Mimomyia (n = 13, 0.06%), Aediomyia (n = 3, 0.01%) and Toxorhynchites (n = 1, 0.004%) appeared low in both districts. Species richness was comparatively higher in Kasese than Arua district, however across villages, it was evenly distributed with no significant differences observed, and species diversity was significantly higher in Arua than Kasese (Mann Whitney U test, p&lt;0.05). A number of species identified here have been implied in arbovirus transmission. Moreover, we show the first description of Culex (Culex) litwakae Harbach mosquito in Uganda, a species previously described in the coastal regions of Kenya. The existence of a mosquito species previously not documented in Uganda suggests a likelihood of many invasive species whose potential to transmit viruses to humans and animals remains largely unknown

Estimation of the number and demographics of companion dogs in the UK

<p>Abstract</p> <p>Background</p> <p>Current estimates of the UK dog population vary, contain potential sources of bias and are based on expensive, large scale, public surveys. Here, we evaluate the potential of a variety of sources for estimation and monitoring of the companion dog population in the UK and associated demographic information. The sources considered were: a public survey; veterinary practices; pet insurance companies; micro-chip records; Kennel Club registrations; and the Pet Travel Scheme. The public survey and subpopulation estimates from veterinary practices, pet insurance companies and Kennel Club registrations, were combined to generate distinct estimates of the UK owned dog population using a Bayesian approach.</p> <p>Results</p> <p>We estimated there are 9.4 (95% CI: 8.1-11.5) million companion dogs in the UK according to the public survey alone, which is similar to other recent estimates. The population was judged to be over-estimated by combining the public and veterinary surveys (16.4, 95% CI: 12.5-21.5 million) and under-estimated by combining the public survey and insured dog numbers (4.8, 95% CI: 3.6-6.9 million). An estimate based on combining the public survey and Kennel Club registered dogs was 7.1 (95% CI: 4.5-12.9) million. Based on Bayesian estimations, 77 (95% CI: 62-92)% of the UK dog population were registered at a veterinary practice; 42 (95% CI: 29-55)% of dogs were insured; and 29 (95% CI: 17-43)% of dogs were Kennel Club registered. Breed demographics suggested the Labrador was consistently the most popular breed registered in micro-chip records, with the Kennel Club and with J. Sainsbury's PLC pet insurance. A comparison of the demographics between these sources suggested that popular working breeds were under-represented and certain toy, utility and miniature breeds were over- represented in the Kennel Club registrations. Density maps were produced from micro-chip records based on the geographical distribution of dogs.</p> <p>Conclusions</p> <p>A list containing the breed of each insured dog was provided by J. Sainsbury's PLC pet insurance without any accompanying information about the dog or owner.</p