Tissue functions mediated by β3-adrenoceptors—findings and challenges

As β3-adrenoceptor agonists metamorphose from experimental tools into therapeutic drugs, it is vital to obtain a comprehensive picture of the cell and tissue functions mediated by this receptor subtype in humans. Human tissues with proven functions and/or a high expression of β3-adrenoceptors include the urinary bladder, the gall bladder, and other parts of the gastrointestinal tract. While several other β3-adrenoceptor functions have been proposed based on results obtained in animals, their relevance to humans remains uncertain. For instance, β3-adrenoceptors perform an important role in thermogenesis and lipolysis in rodent brown and white adipose tissue, respectively, but their role in humans appears less significant. Moreover, the use of tools such as the agonist BRL 37344 and the antagonist SR59230A to demonstrate functional involvement of β3-adrenoceptors may lead in many cases to misleading conclusions as they can also interact with other β-adrenoceptor subtypes or even non-adrenoceptor targets. In conclusion, we propose that many responses attributed to β3-adrenoceptor stimulation may need re-evaluation in the light of the development of more selective tools. Moreover, findings in experimental animals need to be extended to humans in order to better understand the potential additional indications and side effects of the β3-adrenoceptor agonists that are beginning to enter clinical medicine

Decreased thermal tolerance under recurrent heat stress conditions explains summer mass mortality of the blue mussel Mytilus edulis

Extreme events such as heat waves have increased in frequency and duration over the last decades. Under future climate scenarios, these discrete climatic events are expected to become even more recurrent and severe. Heat waves are particularly important on rocky intertidal shores, one of the most thermally variable and stressful habitats on the planet. Intertidal mussels, such as the blue mussel Mytilus edulis, are ecosystem engineers of global ecological and economic importance, that occasionally suffer mass mortalities. This study investigates the potential causes and consequences of a mass mortality event of M. edulis that occurred along the French coast of the eastern English Channel in summer 2018. We used an integrative, climatological and ecophysiological methodology based on three complementary approaches. We first showed that the observed mass mortality (representing 49 to 59% of the annual commercial value of local recreational and professional fisheries combined) occurred under relatively moderate heat wave conditions. This result indicates that M. edulis body temperature is controlled by non-climatic heat sources instead of climatic heat sources, as previously reported for intertidal gastropods. Using biomimetic loggers (i.e. 'robomussels'), we identified four periods of 5 to 6 consecutive days when M. edulis body temperatures consistently reached more than 30 °C, and occasionally more than 35 °C and even more than 40 °C. We subsequently reproduced these body temperature patterns in the laboratory to infer M. edulis thermal tolerance under conditions of repeated heat stress. We found that thermal tolerance consistently decreased with the number of successive daily exposures. These results are discussed in the context of an era of global change where heat events are expected to increase in intensity and frequency, especially in the eastern English Channel where the low frequency of commercially exploitable mussels already questions both their ecological and commercial sustainability.Funding Agency French Ministere de l'Enseignement Superieur et de la Recherche Region Hauts-de-France European Funds for Regional Economical Development Pierre Hubert Curien PESSOA Felloswhip Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) IF/01413/2014/CP1217/CT0004 National Research Foundation - South Africa 64801 South African Research Chairs Initiative (SARChI) of the Department of Science and Technology National Research Foundation - South Africainfo:eu-repo/semantics/publishedVersio

Are researchers deliberately bypassing the technology transfer office? An analysis of TTO awareness

Most universities committed to the commercialization of academic research have established technology transfer offices (TTOs). Nonetheless, many researchers bypass these TTOs and take their inventions directly to the marketplace. While TTO bypassing has typically been portrayed as deliberate and undesirable behavior, we argue that it could be unintentional as many researchers may simply be unaware of the TTO’s existence. Taking an information-processing perspective and using data on 3250 researchers in 24 European universities, we examine researcher attributes associated with TTO awareness. Our evidence confirms that only a minority of researchers are aware of the existence of a TTO at their university. TTO awareness is greater among researchers who possess experience as entrepreneurs, closed many research and consulting contracts with industry partners, conduct research in medicine, engineering or life sciences, or occupy postdoctoral positions. Policy implications of these findings are discussed

The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides

A unifying theme common to the action of many cationic peptides that display lethal activities against microbial pathogens is their specific action at microbial membranes that results in selective loss of ions and small nucleotides chiefly ATP. One model cationic peptide that induces non-lytic release of ATP from the fungal pathogen Candida albicans is salivary histatin 5 (Hst 5). The major characteristic of Hst 5-induced ATP release is that it occurs rapidly while cells are still metabolically active and have polarized membranes, thus precluding cell lysis as the means of release of ATP. Other cationic peptides that induce selective release of ATP from target microbes are lactoferricin, human neutrophil defensins, bactenecin, and cathelicidin peptides. The role of released extracellular ATP induced by cationic peptides is not known, but localized increases in extracellular ATP concentration may serve to potentiate cell killing, facilitate further peptide uptake, or function as an additional signal to activate the host innate immune system at the site of infection

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders

The Role of Tourism and Recreation in the Spread of Non-Native Species: A Systematic Review and Meta-Analysis

Managing the pathways by which non-native species are introduced and spread is considered the most effective way of preventing species invasions. Tourism and outdoor recreation involve the frequent congregation of people, vehicles and vessels from geographically diverse areas. They are therefore perceived to be major pathways for the movement of non-native species, and ones that will become increasingly important with the continued growth of these sectors. However, a global assessment of the relationship between tourism activities and the introduction of non-native species–particularly in freshwater and marine environments–is lacking. We conducted a systematic review and meta-analysis to determine the impact of tourism and outdoor recreation on non-native species in terrestrial, marine and freshwater environments. Our results provide quantitative evidence that the abundance and richness of non-native species are significantly higher in sites where tourist activities take place than in control sites. The pattern was consistent across terrestrial, freshwater and marine environments; across a variety of vectors (e.g. horses, hikers, yachts); and across a range of taxonomic groups. These results highlight the need for widespread biosecurity interventions to prevent the inadvertent introduction of invasive non-native species (INNS) as the tourism and outdoor recreation sectors grow

The effects of implementing a point-of-care electronic template to prompt routine anxiety and depression screening in patients consulting for osteoarthritis (the Primary Care Osteoarthritis Trial): A cluster randomised trial in primary care

Background This study aimed to evaluate whether prompting general practitioners (GPs) to routinely assess and manage anxiety and depression in patients consulting with osteoarthritis (OA) improves pain outcomes. Methods and findings We conducted a cluster randomised controlled trial involving 45 English general practices. In intervention practices, patients aged ≥45 y consulting with OA received point-of-care anxiety and depression screening by the GP, prompted by an automated electronic template comprising five questions (a two-item Patient Health Questionnaire–2 for depression, a two-item Generalized Anxiety Disorder–2 questionnaire for anxiety, and a question about current pain intensity [0–10 numerical rating scale]). The template signposted GPs to follow National Institute for Health and Care Excellence clinical guidelines for anxiety, depression, and OA and was supported by a brief training package. The template in control practices prompted GPs to ask the pain intensity question only. The primary outcome was patient-reported current pain intensity post-consultation and at 3-, 6-, and 12-mo follow-up. Secondary outcomes included pain-related disability, anxiety, depression, and general health. During the trial period, 7,279 patients aged ≥45 y consulted with a relevant OA-related code, and 4,240 patients were deemed potentially eligible by participating GPs. Templates were completed for 2,042 patients (1,339 [31.6%] in the control arm and 703 [23.1%] in the intervention arm). Of these 2,042 patients, 1,412 returned questionnaires (501 [71.3%] from 20 intervention practices, 911 [68.0%] from 24 control practices). Follow-up rates were similar in both arms, totalling 1,093 (77.4%) at 3 mo, 1,064 (75.4%) at 6 mo, and 1,017 (72.0%) at 12 mo. For the primary endpoint, multilevel modelling yielded significantly higher average pain intensity across follow-up to 12 mo in the intervention group than the control group (adjusted mean difference 0.31; 95% CI 0.04, 0.59). Secondary outcomes were consistent with the primary outcome measure in reflecting better outcomes as a whole for the control group than the intervention group. Anxiety and depression scores did not reduce following the intervention. The main limitations of this study are two potential sources of bias: an imbalance in cluster size (mean practice size 7,397 [intervention] versus 5,850 [control]) and a difference in the proportion of patients for whom the GP deactivated the template (33.6% [intervention] versus 27.8% [control]). Conclusions In this study, we observed no beneficial effect on pain outcomes of prompting GPs to routinely screen for and manage comorbid anxiety and depression in patients presenting with symptoms due to OA, with those in the intervention group reporting statistically significantly higher average pain scores over the four follow-up time points than those in the control group. Trial registration ISRCTN registry ISRCTN4072198

Island survivors: population genetic structure and demography of the critically endangered giant lizard of La Gomera, Gallotia bravoana

Background: The giant lizard of La Gomera (Gallotia bravoana), is an endemic lacertid of this Canary Island that lives confined to a very restricted area of occupancy in a steep cliff, and is catalogued as Critically Endangered by IUCN. We present the first population genetic analysis of the wild population as well as of captive-born individuals (for which paternity data are available) from a recovery center. Current genetic variability, and inferred past demographic changes were determined in order to discern the relative contribution of natural versus human-mediated effects on the observed decline in population size. Results: Genetic analyses indicate that the only known natural population of the species shows low genetic diversity and acts as a single evolutionary unit. Demographic analyses inferred a prolonged decline of the species for at least 230 generations. Depending on the assumed generation time, the onset of the decline was dated between 1200-13000 years ago. Pedigree analyses of captive individuals suggest that reproductive behavior of the giant lizard of La Gomera may include polyandry, multiple paternity and female long-term sperm retention. Conclusions: The current low genetic diversity of G. bravoana is the result of a long-term gradual decline. Because generation time is unknown in this lizard and estimates had large credibility intervals, it is not possible to determine the relative contribution of humans in the collapse of the population. Shorter generation times would favor a stronger influence of human pressure whereas longer generation times would favor a climate-induced origin of the decline. In any case, our analyses show that the wild population has survived for a long period of time with low levels of genetic diversity and a small effective population size. Reproductive behavior may have acted as an important inbreeding avoidance mechanism allowing the species to elude extinction. Overall, our results suggest that the species retains its adaptive potential and could restore its ancient genetic diversity under favorable conditions. Therefore, management of the giant lizard of La Gomera should concentrate efforts on enhancing population growth rates through captive breeding of the species as well as on restoring the carrying capacity of its natural habitat.Spanish Ministry of Education; European Life Project [LIFE 02 NAT-E-008614]; Ministerio de Ciencia e Innovacion [REN 2001- 1514/GLO, CGL 2010-18216]info:eu-repo/semantics/publishedVersio

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability