Since the beginning of the 21st Century, synthetic biology has established itself as an effective technological approach to design and engineer biological systems. Whilst research and investment continues to develop the understanding, control and engineering infrastructural platforms necessary to tackle ever more challenging systems - and to increase the precision, robustness, speed and affordability of existing solutions - hundreds of start-up companies, predominantly in the US and UK, are already translating learnings and potential applications into commercially viable tools, services and products. Start-ups and SMEs have been the predominant channel for synthetic biology commercialisation to date, facilitating rapid response to changing societal interests and market pull arising from increasing awareness of health and global sustainability issues. Private investment in start-ups across the US and UK is increasing rapidly and now totals over $12bn. Health-related biotechnology applications have dominated the commercialisation of products to date, but significant opportunities for the production of bio-derived materials and chemicals, including consumer products, are now being developed. Synthetic biology start-ups developing tools and services account for between 10% (in the UK) and ∼25% (in the US) of private investment activity. Around 20% of synthetic biology start-ups address industrial biotechnology targets, but currently, only attract ∼11% private investment. Adopting a more networked approach - linking specialists, infrastructure and ongoing research to de-risk the economic challenges of scale-up and supported by an effective long-term funding strategy - is set to transform the impact of synthetic biology and industrial biotechnology in the bioeconomy. © 2020 The Author(s).The early neuropathological features of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are protein aggregates in motor neurons and microglial activation. Similar pathology characterizes Guamanian ALS/Parkinsonism dementia complex, which may be triggered by the cyanotoxin β-N-methylamino-l-alanine (BMAA). We report here the occurrence of ALS/MND-type pathological changes in vervets (Chlorocebus sabaeus; n = 8) fed oral doses of a dry powder of BMAA HCl salt (210 mg/kg/day) for 140 days. Spinal cords and brains from toxin-exposed vervets were compared to controls fed rice flour (210 mg/kg/day) and to vervets coadministered equal amounts of BMAA and l-serine (210 mg/kg/day). Immunohistochemistry and quantitative image analysis were used to examine markers of ALS/MND and glial activation. UHPLC-MS/MS was used to confirm BMAA exposures in dosed vervets. Motor neuron degeneration was demonstrated in BMAA-dosed vervets by TDP-43+ proteinopathy in anterior horn cells, by reactive astrogliosis, by activated microglia, and by damage to myelinated axons in the lateral corticospinal tracts. Vervets dosed with BMAA + l-serine displayed reduced neuropathological changes. This study demonstrates that chronic dietary exposure to BMAA causes ALS/MND-type pathological changes in the vervet and coadministration of l-serine reduces the amount of reactive gliosis and the number of protein inclusions in motor neurons. © 2020 American Association of Neuropathologists, Inc.CONTEXT The actions of both endogenous incretin hormones during a meal have not previously been characterized. OBJECTIVE Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. DESIGN Randomized, double-blinded, placebo-controlled, crossover design. SETTING On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). PATIENTS OR OTHER PARTICIPANTS Twelve healthy male volunteers. INTERVENTIONS Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min 1000 pmol/kg/min; 20-270 min 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. MAIN OUTCOME MEASURE Baseline-subtracted area under the curve (bsAUC) of C-peptide. RESULTS Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increahy men. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] 2011, Florida established a Prescription Drug Monitoring Program and adopted new regulations for independent pain-management clinics. This paper examines the association of those reforms with drug overdose deaths and other injury fatalities. Florida's post-reform monthly mortality rates - for drug-involved deaths, motor vehicle crashes, and suicides by means other than poisoning - were compared to a counterfactual estimate of what those rates would have been absent reform. The counterfactual was estimated using a Bayesian structural time-series model based on mortality trends in similar states. By December 2013, drug overdose deaths were down -17% (95% CI, -21% to -12%), motor vehicle crash deaths were down -9% (-14%, to -4%), and suicide deaths were unchanged compared to what would be expected in the absence of reform. Florida's opioid psrescribing reform substantially reduced drug overdose deaths. Reforms may also have reduced motor vehicle crash deaths but were not associated with a change in suicides; more research is needed to understand these patterns. Bayesian structural time-series modeling is a promising new approach to interrupted time-series studies. © The Author(s) 2020. AZ191 mouse Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail [email protected] oxygen uptake (V˙O2) kinetics during onset of and recovery from exercise have been shown to provide valuable parameters regarding functional capacity of both chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients. To investigate the influence of comorbidity of COPD in patients with CHF with reduced ejection fraction on recovery from submaximal exercise, 9 CHF-COPD male patients and 10 age-, gender-, and left ventricle ejection fraction (LVEF)-matched CHF patients underwent constant-load exercise tests (CLET) at moderate and high loads. The V˙O2, heart rate (HR), and cardiac output (CO) recovery kinetics were determined for the monoexponential relationship between these variables and time. Within-group analysis showed that the recovery time constant of HR (P0.05 in group vs load analysis). The ventilatory efficiency was related to MRT of V˙O2 during high CLET (r=0.71). Our results suggested that the combination of CHF and COPD may further impair the recovery kinetics compared to CHF alone.