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The emergence of large-scale cooperation during the Holocene remains a central problem in the evolutionary literature. One hypothesis points to culturally evolved beliefs in punishing, interventionist gods that facilitate the extension of cooperative behaviour toward geographically distant co-religionists. Furthermore, another hypothesis points to such mechanisms being constrained to the religious ingroup, possibly at the expense of religious outgroups. To test these hypotheses, we administered two behavioural experiments and a set of interviews to a sample of 2228 participants from 15 diverse populations. These populations included foragers, pastoralists, horticulturalists, and wage labourers, practicing Buddhism, Christianity, and Hinduism, but also forms of animism and ancestor worship. Using the Random Allocation Game (RAG) and the Dictator Game (DG) in which individuals allocated money between themselves, local and geographically distant co-religionists, and religious outgroups, we found that higher ratings of gods as monitoring and punishing predicted decreased local favouritism (RAGs) and increased resource-sharing with distant co-religionists (DGs). The effects of punishing and monitoring gods on outgroup allocations revealed between-site variability, suggesting that in the absence of intergroup hostility, moralizing gods may be implicated in cooperative behaviour toward outgroups. These results provide support for the hypothesis that beliefs in monitoring and punitive gods help expand the circle of sustainable social interaction, and open questions about the treatment of religious outgroups.

The emergence of large-scale cooperation during the Holocene remains a central problem in the evolutionary literature. One hypothesis points to culturally evolved beliefs in punishing, interventionist gods that facilitate the extension of cooperative behaviour toward geographically distant coreligionists. Furthermore, another hypothesis points to such mechanisms being constrained to the religious ingroup, possibly at the expense of religious outgroups. To test these hypotheses, we administered two behavioural experiments and a set of interviews to a sample of 2228 participants from 15 diverse populations. These populations included foragers, pastoralists, horticulturalists, and wage labourers, practicing Buddhism, Christianity, and Hinduism, but also forms of animism and ancestor worship. Using the Random Allocation Game (RAG) and the Dictator Game (DG) in which individuals allocated money between themselves, local and geographically distant co-religionists, and religious outgroups, we found that higher ratings of gods as monitoring and punishing predicted decreased local favouritism (RAGs) and increased resource-sharing with distant co-religionists (DGs). The effects of punishing and monitoring gods on outgroup allocations revealed between-site variability, suggesting that in the absence of intergroup hostility, moralizing gods may be implicated in cooperative behaviour toward outgroups. These results provide support for the hypothesis that beliefs in monitoring and punitive gods help expand the circle of sustainable social interaction, and open questions about the treatment of religious outgroups.

Editor's note: Good point.

Adam Chowaniec, Tundra Semiconductor Corp.'s chief executive, said the difficulty in hiring qualified engineers is leading the Kanata, Ont.-based, high-tech company to take over other firms just to acquire their workforce. Tundra recently bought Quadic Systems Inc. of South Portland, Me., for US$45-million partly to gain its experienced semiconductor engineers. Its data indicate 11 occupations where there are shortages that include managers in production, communications and other services; wholesale trade specialists; auditors, accountants and investment professionals; civil, mechanical and industrial engineers; and machinists. Some shortages could be resolved by paying prospective employees more. Others, where there are simply insufficient trained people, include computer engineers, therapy and assessment professionals, health services support staff, and creative designers and craftspersons. \"Anecdotal evidence suggests that some occupations -- trade specialists, truck drivers, nurses, teachers, systems analysts -- are in shortage,\" HRDC said. \"While this perception is not supported by the data, this does not mean that employers are not experiencing difficulty in finding qualified employees in those occupations.\"

Adam Chowaniec, Tundra Semiconductor Corp.'s chief executive, said the difficulty in hiring qualified engineers is leading the Kanata, Ont.-based, high-tech company to take over other firms just to acquire their workforce. Tundra recently bought Quadic Systems Inc. of South Portland, Me., for US$45-million partly to gain its experienced semiconductor engineers. Its data indicate 11 occupations where there are shortages that include managers in production, communications and other services; wholesale trade specialists; auditors, accountants and investment professionals; civil, mechanical and industrial engineers; and machinists. Some shortages could be resolved by paying prospective employees more. Others, where there are simply insufficient trained people, include computer engineers, therapy and assessment professionals, health services support staff, and creative designers and craftspersons. \"Anecdotal evidence suggests that some occupations -- trade specialists, truck drivers, nurses, teachers, systems analysts -- are in shortage,\" HRDC said. \"While this perception is not supported by the data, this does not mean that employers are not experiencing difficulty in finding qualified employees in those occupations.\"

In Grand Falls-Windsor, [Mike Pinsent] said a few years ago some of the tires caught fire. Town workers buried them yet they continued to burn underground for more than six months. He said that's one of the biggest concerns with stockpiling tires near a municipality. The town also wants the tires gone to make room for a landfill site so that it can get rid of its incinerator. However, Pinsent figures it will take the new company at least a month to collect the tires from his site alone. Each truck can collect only about 2,000 tires at a time. Since April 1, there's been a levy of $3 on all new passenger and light truck tires with a rim size up to 17 inches; and a $9 levy on tires with a rim size greater than 17 inches. The revenue from the levy will be used to offset the costs of the recycling program.

The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6–2.8 Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473 6.54f elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules. Antagonists of Smoothened, a class F GPCR involved in the hedgehog pathway, have been developed to treat some cancers. Here Wang et al. report structures of Smoothened in complex with antagonists and an agonist, and describe how mutations may result in resistance to anti-Smoothened treatment.

In a placebo-controlled trial involving immunosuppressed organ-transplant recipients, oral nicotinamide (500 mg twice daily) for 12 months did not lead to lower numbers of keratinocyte cancers or actinic keratoses.

In the past decade, novel methods using engineered receptors have enabled researchers to manipulate neuronal activity with increased spatial and temporal specificity. One widely used chemogenetic method in mice and rats is the DREADD (designer receptors exclusively activated by designer drugs) system in which a mutated muscarinic G protein-coupled receptor is activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). Recently, the Roth laboratory developed a novel inhibitory DREADD in which a mutated kappa-opioid receptor (KORD) is activated by the pharmacologically inert drug salvinorin B (SalB; Vardy et al, 2015). They demonstrated the feasibility of using KORD to study brain circuits involved in motivated behavior in mice. Here, we used behavioral, electrophysiological, and neuroanatomical methods to demonstrate the feasibility of using the novel KORD to study brain circuits involved in motivated behavior in rats. In Exp. 1, we show that SalB dose-dependently decreased spontaneous and cocaine-induced locomotor activity in rats expressing KORD to midbrain (ventral tegmental area/substantia nigra). In Exp. 2, we show that SalB completely inhibited tonic firing in KORD-expressing putative dopamine neurons in midbrain. In Exp. 3, we used a 'retro-DREADD' dual-virus approach to restrict expression of KORD in ventral subiculum neurons that project to nucleus accumbens shell. We show that KORD activation selectively decreased novel context-induced Fos expression in this projection. Our results indicate that the novel KORD is a promising tool to selectively inactivate brain areas and neural circuits in rat studies of motivated behavior.

Background Our longitudinal study reported cognitive impairment in 43% of people following diagnosis of localised colorectal cancer (CRC) versus 15% in healthy controls ( p  < 0.001) and 50% versus 13% 1–2 years later ( p  < 0.001). Here we evaluate cognitive function and neuroimaging in a subgroup at long-term follow-up. Patients and methods Cancer-free Australian participants in the study, and controls, completed cognitive and functional assessments. Neuroimaging was optional. Blood tests included inflammatory markers, clotting factors, sex hormones and apolipoprotein E genotype. The primary endpoint was demographically and practice effect-corrected cognitive scores comparing CRC survivors with controls over time examined using a linear mixed model, adjusted for baseline performance. Secondary endpoints included cognitive impairment rate using the Global Deficit Score [GDS > 0.5], Functional Deficit Score, blood results and neuroimaging. Results The study included 25 CRC survivors (60% men, median age 72) at mean 9 years after baseline (9 received adjuvant chemotherapy) and 25 controls (44% men, median age 68) at mean 6 years after baseline. There were no significant differences in cognitive scores or proportion with cognitive impairment (16 vs. 8%) between survivors and controls and no evidence of accelerated ageing in CRC survivors. Baseline cognitive performance predicted for subsequent cognitive function. There were no differences in functional tests or blood tests between groups. In 18 participants undergoing neuroimaging, 10 CRC survivors had higher myoinositol levels than 8 controls, and lower volume in the right amygdala and caudate and left hippocampal regions. Conclusions There was no difference in cognitive capacity and function between CRC survivors and controls 6–12 years after diagnosis. Differences in neuroimaging require confirmation in a larger sample. Highlights • No evidence of long term cognitive impairment in colorectal cancer survivors compared to controls 6–12 years after diagnosis • No evidence of accelerated cognitive ageing in colorectal cancer survivors • No evidence of long-term functional impairment in colorectal cancer survivors