Idiothetic Path Integration in the Fruit Fly Drosophila melanogaster

After discovering a small drop of food, hungry flies exhibit a peculiar behavior in which they repeatedly stray from, but then return to, the newly discovered resource. To study this behavior in more detail, we tracked hungry Drosophila as they explored a large arena, focusing on the question of how flies remain near the food. To determine whether flies use external stimuli, we individually eliminated visual, olfactory, and pheromonal cues. In all cases, flies still exhibited a centralized search behavior, suggesting that none of these cues are absolutely required for navigation back to the food. To simultaneously eliminate visual and olfactory cues associated with the position of the food, we constructed an apparatus in which the food could be rapidly translated from the center of the arena. Flies continued to search around the original location, even after the food was moved to a new position. A random search model based on measured locomotor statistics could not reproduce the centered nature of the animal’s trajectory. We conclude that this behavior is best explained by a form of path integration in which the flies use idiothetic cues to search near the location of the food. We argue that the use of path integration to perform a centered local search is not a specialization of Drosophila but rather represents an ancient behavioral mode that is homologous to the more elaborate foraging strategies of central place foragers such as ants

Telmatocola sphagniphila gen. nov., sp. nov., a Novel Dendriform Planctomycete from Northern Wetlands

Members of the phylum Planctomycetes are common inhabitants of northern wetlands. We used barcoded pyrosequencing to survey bacterial diversity in an acidic (pH 4.0) Sphagnum peat sampled from the peat bog Obukhovskoye, European North Russia. A total of 21189 bacterial 16S rRNA gene sequences were obtained, of which 1081 reads (5.1%) belonged to the Planctomycetes. Two-thirds of these sequences affiliated with planctomycete groups for which characterized representatives have not yet been available. Here, we describe two organisms from one of these previously uncultivated planctomycete groups. One isolate, strain OB3, was obtained from the peat sample used in our molecular study, while another strain, SP2T (=DSM 23888T = VKM B-2710T), was isolated from the peat bog Staroselsky moss. Both isolates are represented by aerobic, budding, pink-pigmented, non-motile, spherical cells that are arranged in unusual, dendriform-like structures during growth on solid media. These bacteria are moderately acidophilic and mesophilic, capable of growth at pH 4.0–7.0 (optimum pH 5.0–5.5) and at 6–30°C (optimum 20–26°C). The preferred growth substrates are various heteropolysaccharides and sugars, the latter being utilized only if provided in low concentrations (≤0.025%). In contrast to other described planctomycetes, strains SP2T and OB3 possess weak cellulolytic potential. The major fatty acids are C16:1ω5c, C18:1ω5c, C16:0, and C18:0. Characteristic lipids are the n-C31 polyunsaturated alkene (9–10 double bonds) and C30:1/C32:1 (ω-1) hydroxy fatty acids. The G + C content of the DNA is 58.5–59.0 mol%. Strains SP2T and OB3 share identical 16S rRNA gene sequences, which exhibit only 86 and 87% similarity to those of Gemmata obscuriglobus and Zavarzinella formosa. Based on the characteristics reported here, we propose to classify these novel planctomycetes as representatives of a novel genus and species, Telmatocola sphagniphila gen. nov., sp. nov

Mechanism of membrane fusion induced by vesicular stomatitis virus G protein

The glycoproteins (G proteins) of vesicular stomatitis virus (VSV) and related rhabdoviruses (e.g., rabies virus) mediate both cell attachment and membrane fusion. The reversibility of their fusogenic conformational transitions differentiates them from many other low-pH-induced viral fusion proteins. We report single-virion fusion experiments, using methods developed in previous publications to probe fusion of influenza and West Nile viruses. We show that a three-stage model fits VSV single-particle fusion kinetics: (i) reversible, pH-dependent, G-protein conformational change from the known prefusion conformation to an extended, monomeric intermediate; (ii) reversible trimerization and clustering of the G-protein fusion loops, leading to an extended intermediate that inserts the fusion loops into the target-cell membrane; and (iii) folding back of a cluster of extended trimers into their postfusion conformations, bringing together the viral and cellular membranes. From simulations of the kinetic data, we conclude that the critical number of G-protein trimers required to overcome membrane resistance is 3 to 5, within a contact zone between the virus and the target membrane of 30 to 50 trimers. This sequence of conformational events is similar to those shown to describe fusion by influenza virus hemagglutinin (a “class I” fusogen) and West Nile virus envelope protein (“class II”). Our study of VSV now extends this description to “class III” viral fusion proteins, showing that reversibility of the low-pH-induced transition and architectural differences in the fusion proteins themselves do not change the basic mechanism by which they catalyze membrane fusion

Effect of Deep Brain Stimulation on Parkinson's Nonmotor Symptoms following Unilateral DBS: A Pilot Study

Parkinson's disease (PD) management has traditionally focused largely on motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are effective treatments for motor symptoms. Nonmotor symptoms (NMSs) may also profoundly affect the quality of life. The purpose of this pilot study was to evaluate NMS changes pre- and post-DBS utilizing two recently developed questionnaires. Methods. NMS-Q (questionnaire) and NMS-S (scale) were administered to PD patients before/after unilateral DBS (STN/GPi targets). Results. Ten PD patients (9 STN implants, 1 GPi implant) were included. The three most frequent NMS symptoms identified utilizing NMS-Q in pre-surgical patients were gastrointestinal (100%), sleep (100%), and urinary (90%). NMS sleep subscore significantly decreased (−1.6 points ± 1.8, P = 0.03). The three most frequent NMS symptoms identified in pre-surgical patients using NMS-S were gastrointestinal (90%), mood (80%), and cardiovascular (80%). The largest mean decrease of NMS scores was seen in miscellaneous symptoms (pain, anosmia, weight change, and sweating) (−7 points ± 8.7), and cardiovascular/falls (−1.9, P = 0.02). Conclusion. Non-motor symptoms improved on two separate questionnaires following unilateral DBS for PD. Future studies are needed to confirm these findings and determine their clinical significance as well as to examine the strengths/weaknesses of each questionnaire/scale

Noninvasive In Vivo Imaging to Evaluate Immune Responses and Antimicrobial Therapy against Staphylococcus aureus and USA300 MRSA Skin Infections

Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

Low-dimensional perovskite nanoplatelet synthesis using in situ photophysical monitoring to establish controlled growth.

Perovskite nanoparticles have attracted the attention of research groups around the world for their impressive photophysical properties, facile synthesis and versatile surface chemistry. Here, we report a synthetic route that takes advantage of a suite of soluble precursors to generate CsPbBr3 perovskite nanoplatelets with fine control over size, thickness and optical properties. We demonstrate near unit cell precision, creating well characterized materials with sharp, narrow emission lines at 430, 460 and 490 nm corresponding to nanoplatelets that are 2, 4, and 6 unit cells thick, respectively. Nanoplatelets were characterized with optical spectroscopy, atomic force microscopy, scanning electron microscopy and transmission electron microscopy to explicitly correlate growth conditions, thickness and resulting photophysical properties. Detailed in situ photoluminescence spectroscopic studies were carried out to understand and optimize particle growth by correlating light emission with nanoplatelet growth across a range of synthetic conditions. It was found that nanoplatelet thickness and emission wavelength increase as the ratio of oleic acid to oleyl amine or the reaction temperature is increased. Using this information, we control the lateral size, width and corresponding emission wavelength of the desired nanoplatelets by modulating the temperature and ratios of the ligand

Immune microenvironment dysfunctions enable malignification at the onset of myelodysplastic syndromes

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The Erotic and the Vulgar: Visual Culture and Organized Labor's Critique of U.S. Hegemony in Occupied Japan

This essay engages the colonial legacy of postwar Japan by arguing that the political cartoons produced as part of the postwar Japanese labor movement’s critique of U.S. cultural hegemony illustrate how gendered discourses underpinned, and sometimes undermined, the ideologies formally represented by visual artists and the organizations that funded them. A significant component of organized labor’s propaganda rested on a corpus of visual media that depicted women as icons of Japanese national culture. Japan’s most militant labor unions were propagating anti-imperialist discourses that invoked an engendered/endangered nation that accentuated the importance of union roles for men by subordinating, then eliminating, union roles for women

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio