Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with β-tricalcium phosphate microparticles (mPCL–TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL–TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.     

Changes in work affect in response to lunchtime walking in previously physically inactive employees: A randomized trial

Physical activity may regulate affective experiences at work, but controlled studies are needed and there has been a reliance on retrospective accounts of experience. The purpose of the present study was to examine the effect of lunchtime walks on momentary work affect at the individual and group levels. Physically inactive employees (N = 56; M age = 47.68; 92.86% female) from a large university in the UK were randomized to immediate treatment or delayed treatment (DT). The DT participants completed both a control and intervention period. During the intervention period, participants partook in three weekly 30‐min lunchtime group‐led walks for 10 weeks. They completed twice daily affective reports at work (morning and afternoon) using mobile phones on two randomly chosen days per week. Multilevel modeling was used to analyze the data. Lunchtime walks improved enthusiasm, relaxation, and nervousness at work, although the pattern of results differed depending on whether between‐group or within‐person analyses were conducted. The intervention was effective in changing some affective states and may have broader implications for public health and workplace performance.     

Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice

The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT_1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT_1A receptor-mutant mice. These animals lack functional 5-HT_1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT_1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT_1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT_1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.     

Increasing homogeneity in global food supplies and the implications for food security

The narrowing of diversity in crop species contributing to the world’s food supplies has been considered a potential threat to food security. However, changes in this diversity have not been quantified globally. We assess trends over the past 50 y in the richness, abundance, and composition of crop species in national food supplies worldwide. Over this period, national per capita food supplies expanded in total quantities of food calories, protein, fat, and weight, with increased proportions of those quantities sourcing from energy-dense foods. At the same time the number of measured crop commodities contributing to national food supplies increased, the relative contribution of these commodities within these supplies became more even, and the dominance of the most significant commodities decreased. As a consequence, national food supplies worldwide became more similar in composition, correlated particularly with an increased supply of a number of globally important cereal and oil crops, and a decline of other cereal, oil, and starchy root species. The increase in homogeneity worldwide portends the establishment of a global standard food supply, which is relatively species-rich in regard to measured crops at the national level, but species-poor globally. These changes in food supplies heighten interdependence among countries in regard to availability and access to these food sources and the genetic resources supporting their production, and give further urgency to nutrition development priorities aimed at bolstering food security.A shared axiom of ecology and nutrition is that, within certain ranges, diversity enhances the health and function of complex biological systems. Species diversity has been shown to stimulate productivity, stability, ecosystem services, and resilience in natural (1–5) and in agricultural ecosystems (6–13). Likewise, variation in food species contributing to diet has been associated with nutritional adequacy (14–17) and food security (18).The development of sedentary agricultural societies and further rise of modern agriculture is generally considered to have led to a decline in the total number of plant species upon which humans depend for food (19, 20), particularly the wild, semidomesticated, and cultivated vegetables and fruits, spices, and other food plants that supplemented staple crops with the provision of micronutrients and that bolstered food security historically during crop failures (21). Harlan (20) warned that

most of the food for mankind comes from a small number of crops and the total number is decreasing steadily. In the United States in the past 40 years, many vegetables and fruits have disappeared from the diet, and the trend is going on all over the world. More and more people will be fed by fewer and fewer crops.

More recent analyses of dietary transition in developing countries in association with globalization have noted increases in the diversity of plants contributing to diets locally, along with a Westernization transition in preference of energy-dense foods (i.e., animal products, plant oils, and sugars) over cereals, pulses, and vegetables, and of particular major crop plants within these food categories over traditional crops (22, 23). The impact of such changes on overall crop diversity worldwide has not been comprehensively documented, although recent changes in varietal and allelic level diversity of some crops have been investigated (24–26). Given the potential food security implications of narrowing of the diversity of crop species both in production systems and in food supplies, an assessment of the global state of crop plant species diversity is warranted.Here we examine changes in the diversity of the portfolio of crop species upon which humans primarily depend for food security in regard to calories, protein, fat, and food weight. Using national per capita food supply data published by the Food and Agriculture Organization (FAO) of the United Nations, we analyzed trends in the richness, abundance, and composition of measured crop commodities in the food supplies of 152 countries comprising 98% of the world’s population from 1961 to 2009.     

Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses

Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis.