Xenophagy in herpes simplex virus replication and pathogenesis

Autophagy functions in part as an important host defense mechanism to engulf and degrade intracellular pathogens, a process that has been termed xenophagy. Xenophagy is detrimental to the invading microbe in terms of replication and pathogenesis and many pathogens either dampen the autophagic response, or utilize the pathway to enhance their life cycle. Herpes simplex virus type 1 (HSV-1) counteracts the induction of xenophagy through its neurovirulence protein, ICP34.5. ICP34.5 binds protein phosphatase 1a to counter PKR-mediated phosphorylation of eIF2α, and also binds the autophagy-promoting protein Beclin 1. Through these interactions, ICP34.5 prevents translational arrest and downregulates the formation of autophagosomes. Whereas autophagy antagonism promotes neurovirulence, it has no impact on the replication of HSV-1 in permissive cultured cells. As discussed in this article, this work raises a number of questions as to the mechanism of ICP34.5-mediated inhibition of autophagy, as well as to the role of autophagy antagonism in the lifecycle of HSV-1

Pollination effectiveness of specialist and generalist visitors to a North Carolina population of Claytonia virginica

We measured the pollination effectiveness and visitation rates of major insect visitors of Claytonia virginica, an obligately insect-pollinated spring wildflower, in a North Carolina deciduous forest. Seed set in the population was not pollinator-limited except during rainy weather and very early in the flowering season. The solitary bee Andrena erigeniae and the bee fly Bombylius major were responsible for more than 75% of the visits to C. virginica. Andrena erigeniae is a specialist on C. virginica, while B. major is a common visitor to many plant species. We measured the effectiveness of a pollinator by the probability that a visit resulted in fruit (capsule) formation. For those flowers that were successfully pollinated and thus produced a capsule, number of seeds did not vary with visitor identity or the total number of visits received. Although B. major and female A. erigeniae differ greatly in morphology and foraging behavior, a visit by either insect results in equally high seed set. As B. major is about two-thirds as abundant as A. erigeniae females on C. virginica, both insects contribute substantially to seed set in our population. With the visitation frequency and pollination effectiveness we measured, the generalist B. major alone has the potential to pollinate three-quarters of the flowers

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task

The expression of VvMYBPA1 in tobacco remodulates the phenylpropanoid pathway and diverts the synthesis of anthocyanins into condensed tannins in flowers

Patients in Vegetative State (VS), also known as Unresponsive Wakefulness State (UWS) are deemed to be unaware of themselves or their environment. This is different from patients diagnosed with Minimally Conscious state (MCS), who can have intermittent awareness. In both states, there is a severe impairment of consciousness; these disorders are referred to as disorders of consciousness (DOC) and if the state is prolonged, pDOC. There is growing evidence that some patients who are behaviourally in VS/UWS can show neural activation to environmental stimuli and that this response can be detected using functional brain imaging (fMRI/PET) and electroencephalography (EEG). Recently, it has also been suggested that a more reliable detection of brain responsiveness and hence a more reliable differentiation between VS/UWS and MCS requires person-centred and person-specific stimuli, such as the subject's own name stimulus.In this study we obtained event related potential data (ERP) from 12 healthy subjects and 16 patients in pDOC, five of whom were in the VS/UWS and 11 in the Minimally Conscious State (MCS). We used as the ERP stimuli the subjects' own name, others' names and reversed other names. We performed a sensor level analysis using Statistical Parametric Mapping (SPM) software. Using this paradigm in 4 DOC patients (3 in MCS, and 1 in VS/UWS) we detected a statistically significant difference in EEG response to their own name versus other peoples' names with ERP latencies (~300 ms and ~700 ms post stimuli). Some of these differences were similar to those found in a control group of healthy subjects.This study shows the feasibility of using self-relevant stimuli such as a subject's own name for assessment of brain function in pDOC patients. This neurophysiological test is suitable for bed-side/hospital based assessment of pDOC patients. As it does not require sophisticated scanning equipment it can feasibly be used within a hospital or care setting to help professionals tailor medical and psycho-social management for patients

Chembench: A Publicly Accessible, Integrated Cheminformatics Portal

The enormous increase in the amount of publicly available chemical genomics data and the growing emphasis on data sharing and open science mandates that cheminformaticians also make their models publicly available for broad use by the scientific community. Chembench is one of the first publicly accessible, integrated cheminformatics Web portals. It has been extensively used by researchers from different fields for curation, visualization, analysis, and modeling of chemogenomics data. Since its launch in 2008, Chembench has been accessed more than 1 million times by more than 5000 users from a total of 98 countries. We report on the recent updates and improvements that increase the simplicity of use, computational efficiency, accuracy, and accessibility of a broad range of tools and services for computer-assisted drug design and computational toxicology available on Chembench. Chembench remains freely accessible at https://chembench.mml.unc.ed

Marginal Reefs Under Stress: Physiological Limits Render Galápagos Corals Susceptible to Ocean Acidification and Thermal Stress

Ocean acidification (OA) and thermal stress may undermine corals' ability to calcify and support diverse reef communities, particularly in marginal environments. Coral calcification depends on aragonite supersaturation (Ω » 1) of the calcifying fluid (cf) from which the skeleton precipitates. Corals actively upregulate pHcf relative to seawater to buffer against changes in temperature and dissolved inorganic carbon, which together control Ωcf. Here we assess the buffering capacity of modern and fossil corals from the Galápagos Islands that have been exposed to sub-optimal conditions, extreme thermal stress, and OA. We demonstrate a significant decline in pHcf and Ωcf since the pre-industrial era, trends which are exacerbated during extreme warm years. These results suggest that there are likely physiological limits to corals' pH buffering capacity, and that these constraints render marginal reefs particularly susceptible to OA

The Benefits and Limits of Urban Tree Planting for Environmental and Human Health

Many of the world's major cities have implemented tree planting programs based on assumed environmental and social benefits of urban forests. Recent studies have increasingly tested these assumptions and provide empirical evidence for the contributions of tree planting programs, as well as their feasibility and limits, for solving or mitigating urban environmental and social issues. We propose that current evidence supports local cooling, stormwater absorption, and health benefits of urban trees for local residents. However, the potential for urban trees to appreciably mitigate greenhouse gas emissions and air pollution over a wide array of sites and environmental conditions is limited. Consequently, urban trees appear to be more promising for climate and pollution adaptation strategies than mitigation strategies. In large part, this is due to space constraints limiting the extent of urban tree canopies relative to the current magnitude of emissions. The most promising environmental and health impacts of urban trees are those that can be realized with well-stewarded tree planting and localized design interventions at site to municipal scales. Tree planting at these scales has documented benefits on local climate and health, which can be maximized through targeted site design followed by monitoring, adaptive management, and studies of long-term eco-evolutionary dynamics.Peer reviewe

Global public policy, transnational policy communities, and their networks

Public policy has been a prisoner of the word "state." Yet, the state is reconfigured by globalization. Through "global public–private partnerships" and "transnational executive networks," new forms of authority are emerging through global and regional policy processes that coexist alongside nation-state policy processes. Accordingly, this article asks what is "global public policy"? The first part of the article identifies new public spaces where global policies occur. These spaces are multiple in character and variety and will be collectively referred to as the "global agora." The second section adapts the conventional policy cycle heuristic by conceptually stretching it to the global and regional levels to reveal the higher degree of pluralization of actors and multiple-authority structures than is the case at national levels. The third section asks: who is involved in the delivery of global public policy? The focus is on transnational policy communities. The global agora is a public space of policymaking and administration, although it is one where authority is more diffuse, decision making is dispersed and sovereignty muddled. Trapped by methodological nationalism and an intellectual agoraphobia of globalization, public policy scholars have yet to examine fully global policy processes and new managerial modes of transnational public administration