Six Steps for Profitable and Environmentally Sound Management of Crop Pests

PaperHow to balance control of pests with profitable crop production and environmental protection

Tomographic reconstruction of neopterous Carboniferous insect nymphs

Two new polyneopteran insect nymphs from the Montceau-les-Mines Lagerstätte of France are presented. Both are preserved in three dimensions, and are imaged with the aid of X-ray micro-tomography, allowing their morphology to be recovered in unprecedented detail. One–Anebos phrixos gen. et sp. nov.–is of uncertain affinities, and preserves portions of the antennae and eyes, coupled with a heavily spined habitus. The other is a roachoid with long antennae and chewing mouthparts very similar in form to the most generalized mandibulate mouthparts of extant orthopteroid insects. Computer reconstructions reveal limbs in both specimens, allowing identification of the segments and annulation in the tarsus, while poorly developed thoracic wing pads suggest both are young instars. This work describes the morphologically best-known Palaeozoic insect nymphs, allowing a better understanding of the juveniles’ palaeobiology and palaeoecology. We also consider the validity of evidence from Palaeozoic juvenile insects in wing origin theories. The study of juvenile Palaeozoic insects is currently a neglected field, yet these fossils provide direct evidence on the evolution of insect development. It is hoped this study will stimulate a renewed interest in such work

A biochemical study of Chinese and Caucasoids

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37454/1/1330130106_ftp.pd

Ontogeny of Human IgE-expressing B Cells and Plasma Cells

BACKGROUND: IgE‐expressing (IgE(+)) plasma cells (PCs) provide a continuous source of allergen‐specific IgE that is central to allergic responses. The extreme sparsity of IgE(+) cells in vivo has confined their study almost entirely to mouse models. OBJECTIVE: To characterize the development pathway of human IgE(+) PCs and to determine the ontogeny of human IgE(+) PCs. METHODS: To generate human IgE(+) cells, we cultured tonsil B cells with IL‐4 and anti‐CD40. Using FACS and RT‐PCR, we examined the phenotype of generated IgE(+) cells, the capacity of tonsil B‐cell subsets to generate IgE(+) PCs and the class switching pathways involved. RESULTS: We have identified three phenotypic stages of IgE(+) PC development pathway, namely (i) IgE(+)germinal centre (GC)‐like B cells, (ii) IgE(+) PC‐like ‘plasmablasts’ and (iii) IgE(+) PCs. The same phenotypic stages were also observed for IgG1(+) cells. Total tonsil B cells give rise to IgE(+) PCs by direct and sequential switching, whereas the isolated GC B‐cell fraction, the main source of IgE(+) PCs, generates IgE(+) PCs by sequential switching. PC differentiation of IgE(+) cells is accompanied by the down‐regulation of surface expression of the short form of membrane IgE (mIgE(S)), which is homologous to mouse mIgE, and the up‐regulation of the long form of mIgE (mIgE(L)), which is associated with an enhanced B‐cell survival and expressed in humans, but not in mice. CONCLUSION: Generation of IgE(+) PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgE(L)/mIgE(S) ratio may be implicated in survival of IgE(+) B cells during PC differentiation and allergic disease

A powerful intervention: general practitioners' use of sickness certification in depression

<b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

High-Affinity Small Molecule Inhibitors of T Cell Costimulation: Compounds for Immunotherapy

SummaryCostimulatory molecules are important regulators of T cell activation and thus favored targets for therapeutic manipulation of immune responses. One of the key costimulatory receptors is CD80, which binds the T cell ligands, CD28, and CTLA-4. We describe a set of small compounds that bind with high specificity and low nanomolar affinity to CD80. The compounds have relatively slow off-rates and block both CD28 and CTLA-4 binding, implying that they occlude the shared ligand binding site. The compounds inhibit proinflammatory cytokine release in T cell assays with submicromolar potency, and as such, they represent promising leads for the development of novel therapeutics for immune-mediated inflammatory disease. Our results also suggest that other predominantly β proteins, such as those that dominate the cell surface, may also be accessible as potentially therapeutic targets

Sampling molecular conformations and dynamics in a multiuser virtual reality framework

Copyright © 2018 The Authors, some rights reserved. We describe a framework for interactive molecular dynamics in a multiuser virtual reality (VR) environment, combining rigorous cloud-mounted atomistic physics simulations with commodity VR hardware, which we have made accessible to readers (see isci.itch.io/nsb-imd). It allows users to visualize and sample, with atomic-level precision, the structures and dynamics of complex molecular structures “on the fly” and to interact with other users in the same virtual environment. A series of controlled studies, in which participants were tasked with a range of molecular manipulation goals (threading methane through a nanotube, changing helical screw sense, and tying a protein knot), quantitatively demonstrate that users within the interactive VR environment can complete sophisticated molecular modeling tasks more quickly than they can using conventional interfaces, especially for molecular pathways and structural transitions whose conformational choreographies are intrinsically three-dimensional. This framework should accelerate progress in nanoscale molecular engineering areas including conformational mapping, drug development, synthetic biology, and catalyst design. More broadly, our findings highlight the potential of VR in scientific domains where three-dimensional dynamics matter, spanning research and education

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy