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Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.

Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5–7 day brain infarct volume was measured by computed tomography. Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.

Wild bee populations have undergone declines in recent years across much of the Western world, and these declines have the potential to limit yield in pollination-dependent crops. Highbush blueberry, Vaccinium corymbosum, and tart cherry, Prunus cerasus, are spring-blooming crops that rely on the movement of pollen by bees and other insects for pollination. Wild bee populations can be increased on farmland by providing floral resources, but whether the addition of these plants translates into increased pollinator density on crop flowers has not been documented in most cropping systems. To determine the importance of providing additional floral resources for wild bee pollinator communities, we selected blueberry fields and tart cherry orchards with and without herbaceous floral enhancements in western Michigan, USA. The bee communities visiting crop flowers, enhancements and control grassy field margins were sampled over a 5-yr period. In addition, the pollen diets of the most abundant wild bee crop pollinators were quantified across Michigan to better understand their foraging niches and to identify potentially important alternative host plants. The presence of floral enhancements did not increase the abundance of wild bees on either blueberry or cherry flowers during bloom. The bee community visiting blueberry was evenly composed of short-season bees that fly only during the spring and long-season bees that fly in both spring and summer. In contrast, the bee community visiting cherry was dominated by short-season spring bees. The majority of pollen collected by the wild bee communities visiting blueberry and cherry was from spring-flowering woody plants, with limited use of the herbaceous enhancements. Enhancements attracted greater abundance and species richness of bees compared to control areas, including twice as many floral specialists. Conserving summer-flying, grassland-associated bees is an appropriate goal for pollinator conservation programs. However, herbaceous enhancements may not provide adequate resources for the wild bees that pollinate spring-flowering crops. This study demonstrates that an examination of the pollen collected by wild bees across their flight periods can identify plant species to help them persist in intensively managed landscapes.

Key Points Several cytokines are induced rapidly after acute brain injury. They are expressed in a temporal and spatial pattern that is consistent with their involvement in subsequent neuronal death. Studies on the role of exogenous and endogenous cytokines in vivo and in vitro have yielded conflicting data. In general terms, interleukin 1 seems to contribute directly to neurodegeneration, whereas transforming growth factor-β is neuroprotective. Tumour necrosis factor-α can both enhance and inhibit neuronal injury; this dual action probably depends on the time course and level of its expression. The complex actions and putative mechanisms of cytokines in the nervous system are similar to their functions in the periphery. Cytokines can act at very low concentrations on numerous cell types within or outside the brain. It is likely that the contribution of cytokines to neurodegeneration does not involve a single mechanism on one specific cell type, but rather depends on several actions, which might be detrimental or beneficial. The primary mechanisms that regulate cytokine bioavailability, and the sites and mechanisms of action that result in neuronal death, have begun to be identified. Similarly, the pathways that transduce cytokine signalling and the interactions between these pathways are beginning to be understood. These insights will allow more effective interventions for the treatment of stroke and other types of brain injury. Cytokines have been implicated as mediators and inhibitors of diverse forms of neurodegeneration. They are induced in response to brain injury and have diverse actions that can cause, exacerbate, mediate and/or inhibit cellular injury and repair. Here we review evidence for the contribution of cytokines to acute neurodegeneration, focusing primarily on interleukin 1 (IL-1), tumour necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ). TGFβ seems to exert primarily neuroprotective actions, whereas TNFα might contribute to neuronal injury and exert protective effects. IL-1 mediates ischaemic, excitotoxic and traumatic brain injury, probably through multiple actions on glia, neurons and the vasculature. Understanding cytokine action in acute neurodegeneration could lead to novel and effective therapeutic strategies, some of which are already in clinical trials.

Background and purpose: Interleukin (IL)‐1 is a key mediator of inflammatory and host defence responses and its effects in the brain are mediated primarily via effects on glia. IL‐1 induces release of inflammatory mediators such as IL‐6 from glia via the type‐1 receptor (IL‐1R1) and established signalling mechanisms including mitogen‐activated protein kinases and nuclear factor kappa‐B. IL‐1 also modifies physiological functions via actions on neurones, through activation of the neutral sphingomyelinase (nSMase)/Src kinase signalling pathway, although the mechanism of IL‐1‐induced IL‐6 synthesis in neurones remains unknown. Experimental approach: Primary mouse neuronal cell cultures, ELISA, Western blot and immunocytochemistry techniques were used. Key results: We show here that IL‐1β induces the synthesis of IL‐6 in primary mouse neuronal cultures, and this is dependent on the activation of IL‐1R1, nSMase and Src kinase. We demonstrate that IL‐1β‐induced Src kinase activation triggers the phosphorylation of the NMDA receptor NR2B subunit, leading to activation of Ca2+/calmodulin‐dependent protein kinase II (CamKII) and the nuclear transcription factor CREB. We also show that NR2B, CamKII and CREB are essential signalling elements involved in IL‐1β‐induced IL‐6 synthesis in neurones. Conclusions and implications: These results demonstrate that IL‐1 interacts with the same receptors on neurones and glia to elicit IL‐6 release, but does so via distinct signalling pathways. The mechanism by which IL‐1β induces IL‐6 synthesis in neurones could be critical in both physiological and pathophysiological actions of IL‐1β, and may provide a new therapeutic target for the treatment of acute CNS injury. British Journal of Pharmacology (2008) 153, 775–783; doi:10.1038/sj.bjp.0707610; published online 3 December 2007

Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, injection of leptin increased levels of the prionflammatory cytokine IL-1β in the hypothalamus of normal Sprague-Dawley rats. Central injection of IL-1 receptor antagonist (IL-1ra) inhibited the suppression of food intake caused by central or peripheral injection of leptin (60 and 84%, respectively) and abolished the leptin-induced increase in body temperature in both cases. Mice lacking (gene knockout) the main IL-1 receptor (80 kDa, R1) responsible for IL-1 actions showed no reduction in food intake in response to leptin. These data indicate that leptin actions in the brain depend on IL-1, and we show further that the effect of leptin on fever, but not food intake, is abolished by a cyclooxygenase inhibitor. Thus, we propose that in addition to its role in body weight regulation, leptin may mediate neuroimmune responses via actions in the brain dependent on release of IL-1 and prostaglandins.

Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on society. Despite this, pharmacological treatment options are limited. Appropriate animal modelling of SAH is essential for the development of neuroprotective drugs, but experimental SAH often fails to produce widespread neuronal loss, as frequently seen in humans. We report that a recently described modification of the endovascular perforation model in rat produced widespread heterogeneous infarcts 72 h after SAH. Cerebral blood flow (CBF) was monitored, with or without intracranial pressure (ICP) measurement, for 1 h after induction of SAH. Blood load size was assessed, and brain injury was quantified at 72 h using histological staining, blood brain barrier breakdown assessment and immunofluorescent imaging of neuronal viability and microglial activation. Results showed that ICP measurement allowed for faster recovery of CBF, potentially reducing brain injury. Larger subarachnoid blood loads predicted more extensive neuronal damage which was easily quantified with the combination of histological and immunohistochemical techniques. Thus, for the investigation of neuroprotective strategies after SAH, the present protocol produces quantifiable, clinically relevant, heterogeneous patterns of infarct due to large blood loads, high ICP and low CBF.

Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL-1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1β on food-motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1β but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1β. In each case, the dose of IL-1ra was 100- to 1000-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous.

INTERNATIONAL JOURNAL OF OBESITY: (2001) 25, 1272-1274

The interleukin-1 (IL-1) family comprises IL-1α and IL-1β and an endogenous IL-1 receptor antagonist (IL-1ra). 1 IL-1 has diverse actions in the brain and has been implicated in both acute and chronic neurodegeneration. 1,2 However, neither IL-1α nor IL-1β are neurotoxic per se in vivo , so other IL-1 related ligands may be important in neurodegeneration. The cytokine interleukin-18 (also called interferon gamma inducing factor, IGIF) was first isolated from the liver of mice during toxic shock. 3 It was later proposed as a member of the IL-1 family, based on protein sequence homology with IL-1β and IL-1ra, and has tentatively been called IL-1γ. 4 We cloned IL-18 from adult rat brain and demonstrated, by RT-PCR, that it is expressed constitutively in cerebellum, hippocampus, hypothalamus, cortex and striatum. Rat brain IL-18 shows close homology to mouse 3 and human IL-18, 5 and to the recently published sequence from the rat adrenal gland. 6 Mouse pro-IL-18 and pro-IL-1β are processed by caspase-1. 7,8 We demonstrate that caspase-1 also cleaves rat IL-18 in vitro and that the caspase inhibitor, zVAD-DCB inhibits this cleavage.