bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proprioceptive neurons of larvalDrosophila melanogastershow direction selective activity requiring the mechanosensory channel TMC
Authors: He Liping , Gulyanon Sarun , Skanata Mirna Mihovilovic , Karagyozov Doycho , Heckscher Ellie , Krieg Michael , Tsechpenakis Gavriil , Gershow Marc , Tracey W. Daniel 
Published: November 2018

AbstractDrosophilaTransmembrane channel-like (Tmc) is a protein that functions in larval proprioception. The closely related TMC1 protein is required for mammalian hearing, and is a pore forming subunit of the hair cell mechanotransduction channel. In hair cells, TMC1 is gated by small deflections of microvilli that produce tension on extracellular tip-links that connect adjacent villi. How Tmc might be gated in larval proprioceptors, which are neurons having a morphology that is completely distinct from hair cells, is unknown. Here, we have used high-speed confocal microscopy to both measure displacements of proprioceptive sensory dendrites during larval movement, and to optically measure neural activity of the moving proprioceptors. Unexpectedly, the pattern of dendrite deformation for distinct neurons was unique and differed depending on the direction of locomotion: ddaE neuron dendrites were strongly curved by forward locomotion while the dendrites of ddaD were more strongly deformed by backward locomotion. Furthermore, GCaMP6f calcium signals recorded in the proprioceptive neurons during locomotion indicated tuning to the direction of movement. ddaE showed strong activation during forward locomotion while ddaD showed responses that were strongest during backwards locomotion. Peripheral proprioceptive neurons in animals mutant forTmcshowed a near complete loss of movement related calcium signals. As the strength of the responses of wild type animals was correlated with dendrite curvature, we propose that Tmc channels may be activated by membrane curvature in dendrites that are exposed to strain. Our findings begin to explain how distinct cellular systems rely on a common molecular pathway for mechanosensory responses.
Perceptron learning and classification in a modeled cortical pyramidal cell
Authors: Moldwin Toviah , Segev Idan 
Published: November 2018

AbstractThe perceptron learning algorithm and its multiple-layer extension, the backpropagation algorithm, are the foundations of the present-day machine learning revolution. However, these algorithms utilize a highly simplified mathematical abstraction of a neuron; it is not clear to what extent real biophysical neurons with morphologically-extended nonlinear dendritic trees and conductance-based synapses could realize perceptron-like learning. Here we implemented the perceptron learning algorithm in a realistic biophysical model of a layer 5 cortical pyramidal cell. We tested this biophysical perceptron (BP) on a memorization task, where it needs to correctly binarily classify 100, 1000, or 2000 patterns, and a generalization task, where it should discriminate between two “noisy” patterns. We show that the BP performs these tasks with an accuracy comparable to that of the original perceptron, though the memorization capacity of the apical tuft is somewhat limited. We concluded that cortical pyramidal neurons can act as powerful classification devices.
Profiles of circulating histidine-rich glycoprotein associate with chronological age and risk of all-cause mortality
Authors: Hong Mun-Gwan , Dodig-Crnković Tea , Chen Xu , Drobin Kimi , Lee Woojoo , Wang Yunzhang , Edfors Fredrik , Kotol David , Thomas Cecilia Engel , Sjöberg Ronald , Odeberg Jacob , Hamsten Anders , Silveira Angela , Hall Per , Nilsson Peter , Pawitan Yudi , Hägg Sara , Uhlén Mathias , Pedersen Nancy L. , Magnusson Patrik K. E. , Schwenk Jochen M. 
Published: November 2018

1.SUMMARYDespite recognizing aging as risk factor of human diseases, little is still known about the molecular traits of biological age and mortality risk. To identify age-associated proteins circulating human blood, we screened 156 subjects aged 50-92 years using an exploratory and multiplexed affinity proteomics approach. We corroborated the top age-associated protein profile (adjusted P < 0.001) in eight additional study sets (N = 4,044 individuals), and confirmed a consistent age-associated increase (P = 6.61 × 10-6) by meta-analysis. Applying antibody validation determined circulating histidine-rich glycoprotein (HRG) as the target, and we observed that sequence variants influenced the antibodies ability to bind to the protein. Profiles of circulating HRG were associated to several clinical traits and predicted the risk of mortality during a follow-up period of 8.5 years (IQR = 7.7-9.3 years) after blood sampling (HR = 1.25 per SD; 95% CI = 1.12-1.39; P = 7.41 × 10-5). In conclusion, our affinity proteomics analysis found associations between the molecular traits of circulating HRG with age and all-cause mortality. This suggests that the profiles of multi-purpose protein HRG could serve as an accessible indicator of physiological processes related to aging.
A Double-Blind Pilot Dosing Study of Low Field Magnetic Stimulation (LFMS) for Treatment-Resistant Depression (TRD)
Authors: Dubin Marc J. , Ilieva Irena , Deng Zhi-De , Thomas Jeena , Cochran Ashly , Kravets Kamilla , Brody Benjamin D. , Christos Paul J. , Kocsis James H. , Liston Conor , Gunning Faith M. 
Published: November 2018

AbstractLow Field Magnetic Stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-minute session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. In a double-blind randomized controlled trial, 30 participants (age 21–65) with treatment-resistant depression were randomized to three 20-minute active or sham LFMS treatments with 48 hours between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. Following the third session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F(1, 24) = 7.45, p = 0.03, Holm-Bonferroni corrected; F(1,22) = 6.92, p = 0.03, Holm-Bonferroni corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. Three 20-minute LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment course as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.
Prawn aquaculture as a method for schistosomiasis control and poverty alleviation: a win-win approach to address a critical infectious disease of poverty
Authors: Hoover Christopher M. , Sokolow Susanne H. , Kemp Jonas , Sanchirico James N. , Lund Andrea J. , Jones Isabel , Higginson Tyler , Riveau Gilles , Savaya-Alkalay Amit , Coyle Shawn , Wood Chelsea L. , Micheli Fiorenza , Casagrandi Renato , Mari Lorenzo , Gatto Marino , Rinaldo Andrea , Perez-Saez Javier , Rohr Jason R. , Sagi Amir , Remais Justin V. , Leo Giulio A. De 
Published: November 2018

AbstractRecent evidence suggests crustacean snail predators may aid schistosomiasis control programs by targeting the environmental component of the parasite’s life cycle through predation of the snail species that serve as intermediate hosts of the parasite. We evaluate costs, benefits, and potential synergies between schistosomiasis control and aquaculture of giant prawns using an integrated bio-economic-epidemiologic model. We identified combinations of stocking density and aquaculture cycle length that maximize profit and offer disease control benefits for sustainable schistosomiasis control. We consider two prawn species in sub-Saharan Africa: the endemic, non-domesticatedMacrobrachium vollenhovenii, and the non-native, domesticatedMacrobrachium rosenbergii. We find that, at profit-optimal densities, bothM. rosenbergiiandM. vollenhoveniican complement conventional control approaches (mass drug treatment of people) and lead to sustainable schistosomiasis control. We conclude that integrated aquaculture strategies can be a win-win strategy in terms of health and sustainable development in schistosomiasis endemic regions of the world.
The DeepTune framework for modeling and characterizing neurons in visual cortex area V4
Authors: Abbasi-Asl Reza , Chen Yuansi , Bloniarz Adam , Oliver Michael , Willmore Ben D.B. , Gallant Jack L. , Yu Bin 
Published: November 2018

AbstractDeep neural network models have recently been shown to be effective in predicting single neuron responses in primate visual cortex areas V4. Despite their high predictive accuracy, these models are generally difficult to interpret. This limits their applicability in characterizing V4 neuron function. Here, we propose the DeepTune framework as a way to elicit interpretations of deep neural network-based models of single neurons in area V4. V4 is a midtier visual cortical area in the ventral visual pathway. Its functional role is not yet well understood. Using a dataset of recordings of 71 V4 neurons stimulated with thousands of static natural images, we build an ensemble of 18 neural network-based models per neuron that accurately predict its response given a stimulus image. To interpret and visualize these models, we use a stability criterion to form optimal stimuli (DeepTune images) by pooling the 18 models together. These DeepTune images not only confirm previous findings on the presence of diverse shape and texture tuning in area V4, but also provide rich, concrete and naturalistic characterization of receptive fields of individual V4 neurons. The population analysis of DeepTune images for 71 neurons reveals how different types of curvature tuning are distributed in V4. In addition, it also suggests strong suppressive tuning for nearly half of the V4 neurons. Though we focus exclusively on the area V4, the DeepTune framework could be applied more generally to enhance the understanding of other visual cortex areas.
Long-term exposure to PFE-360 in the AAV-α-synuclein rat model: findings and implications
Authors: Andersen Michael Aagaard , Sotty Florence , Jensen Poul Henning , Badolo Lassina , Jeggo Ross , Smith Garrick Paul , Christensen Kenneth Vielsted 
Published: November 2018

Significance statementTreatment of Parkinson’s disease is reliant on symptomatic treatments, without any option to slow or halt disease progression. Mutations in LRRK2 and α-synuclein are known risk factors for Parkinson’s disease. Presence of α-synuclein aggregates at autopsies in both idiopathic and most G2019S cases is suggestive of a common disease pathogenesis. LRRK2 and α-synuclein interaction is hypothesized to play a pivotal role in the pathological mechanisms and inhibitors of LRRK2 are investigated as novel disease modulatory treatments in the clinic. However, preclinical in vivo evidence of a beneficial effect of LRRK2 inhibition is mixed and limited. This study increases our understanding of LRRK2 as a mediator of neuronal dysfunction and the potential of LRRK2 as a promising target in PD.
Suppression and facilitation of motion perception in humans
Authors: Tzvetanov Tzvetomir 
Published: November 2018

AbstractIn a study that investigated the putative neuronal origin of suppression and facilitation in human motion perception Schallmo et al. (2018) used various techniques to investigate how motion perception is shaped by excitatory and inhibitory interactions within hMT+ or earlier areas. They further proposed that neuronal normalization is a sufficient account of the behavioural results, discounting accepted and precise neuronal mechanisms of excitation or inhibition. In this Research Advance, it is shown (1) that once the full computational model that predicts the psychophysical results is defined, it is not “divisive normalization” but actually excitatory and inhibitory processes that are the neuronal mechanisms shaping facilitation and suppression in the behavioural domain, then (2) that the experimental design they used allows a quantitative comparison and usage of such “contrast–size tuning” data.
A mutant bacteriophage evolved to infect resistant bacteria gained a broader host range
Authors: Habusha Michal , Tzipilevich Elhanan , Ben-Yehuda Sigal 
Published: November 2018

SummaryBacteriophages (phages) are the most abundant entities in nature, yet little is known about their capacity to acquire new hosts and invade new niches. By exploiting the Gram positive soil bacteriumBacillus subtilis(B. subtilis) and its lytic phage SPO1 as a model, we followed the co-evolution of bacteria and phages. After infection, phage resistant bacteria were readily isolated. These bacteria were defective in production of glycosylated wall teichoic acid (TA) polymers, served as SPO1 receptor. Subsequently, a SPO1 mutant phage that could infect the resistant bacteria evolved. The emerging phage contained mutations in two genes, encoding the baseplate and fibers required for host attachment. Remarkably, the mutant phage gained the capacity to infect non-hostBacillusspecies that are not infected by the wild type phage. We provide evidence that the evolved phage lost its dependency on the species specific glycosylation pattern of TA polymers. Instead, the mutant phage gained the capacity to directly adhere to the TA backbone, conserved among different species, thereby crossing the species barrier.
Shifts in microbial transcription patterns prior to onset of Necrotizing enterocolitis may indicate low oxygen levels in the gut
Authors: Sher Yonatan , Olm Matthew R. , Raveh-Sadka Tali , Brown Christopher , Sher Ruth , Firek Brian , Baker Robyn , Morowitz Michael , Banfield Jillian F. 
Published: November 2018

SummaryPremature infants are at risk for developing necrotizing enterocolitis (NEC), an inflammatory disease that can progress to necrosis of gut tissue. Previous attempts have failed to identify any consistent predictor of NEC. We hypothesized that prior to the appearance of NEC symptoms, the gut microbiome shifts in its transcriptional profile. To test this hypothesis we integrated genome-resolved metagenomic and metatranscriptomic data from multiple time-points in the first month of life of four preterm infants, two of whom later developed NEC. Gut microbiomes of NEC infants showed increased transcription of high oxygen affinity cytochrome oxidases and lower transcription of genes to detoxify nitric oxide, an antimicrobial compound released by host cells. These results, and high transcription of H2 production genes, suggest low O2 conditions prior to NEC onset, and are consistent with hypoxic conditions in diseased gut tissue. The findings motivate further testing of transcript data as a predictor of NEC.HighlightsTranscription of high oxygen affinity microbial cytochrome oxidase may predict necrotizing enterocolitis (NEC) development.Lower transcription of microbial genes to detoxify nitric oxide (NO) may also predict NEC development.Higher transcription of H2 production genes by Escherichia sp. was found in the gut of premature infants that develop NEC.
Nano immunoconjugates crossing blood-brain barrier activate local brain tumor immune system for glioma treatment
Authors: Galstyan Anna , Chiechi Antonella , Korman Alan J. , Sun Tao , Israel Liron L. , Braubach Oliver , Patil Rameshwar , Shatalova Ekaterina , Ljubimov Vladimir A. , Markman Janet , Grodzinski Zachary , Black Keith L. , Penichet Manuel L. , Holler Eggehard , Ljubimov Alexander V. , Ding Hui , Ljubimova Julia Y. 
Published: November 2018

AbstractTreatment of brain gliomas with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross the blood-brain barrier (BBB). We describe a new generation of nano immunoconjugates (NICs) developed on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 and/or a-PD-1 for delivery across the BBB and activation of local brain anti-tumor immune response in glioma-bearing mice. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) resulted in an increase of CD8+ T-cells with a decrease of T regulatory cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with combination of NICs was significantly longer compared to animals treated by single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of nanopolymer-conjugated checkpoint inhibitors as an effective treatment of GBM via activation of both systemic and local brain tumor immune response.
Michigan Neural Distinctiveness (MiND) project: Investigating the scope, causes, and consequences of age-related neural dedifferentiation
Authors: Gagnon Holly , Simmonite Molly , Cassady Kaitlin , Chamberlain Jordan D. , Freiburger Erin , Lalwani Poortata , Kelley Shannon , Foerster Bradley , Park Denise C. , Petrou Myria , Seidler Rachael D. , Taylor Stephan F. , Weissman Daniel H. , Polk Thad A. 
Published: November 2018

AbstractBackgroundAging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).Methods/DesignThe MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI) sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take (1) a benzodiazepine (lorazepam) that should increase GABA activity or (2) a placebo.DiscussionBy collecting multimodal imaging measures (fMRI, MRS, DWI) along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.
Differential binding cell-SELEX method to identify cell-specific aptamers using high-throughput sequencing
Authors: Pleiko Karlis , Saulite Liga , Parfejevs Vadims , Miculis Karlis , Vjaters Egils , Riekstina Una 
Published: November 2018

ABSTRACTAptamers have in recent years emerged as a viable alternative to antibodies. High-throughput sequencing (HTS) has revolutionized aptamer research by increasing the number of reads from a few (using Sanger sequencing) to millions (using an HTS approach). Despite the availability and advantages of HTS compared to Sanger sequencing, there are only 50 aptamer HTS sequencing samples available on public databases. HTS data in aptamer research are primarily used to compare sequence enrichment between subsequent selection cycles. This approach does not take full advantage of HTS because the enrichment of sequences during selection can be due to inefficient negative selection when using live cells. Here, we present a differential binding cell-SELEX (systematic evolution of ligands by exponential enrichment) workflow that adapts theFASTAptamertoolbox and bioinformatics tooledgeR, which are primarily used for functional genomics, to achieve more informative metrics about the selection process. We propose a fast and practical high-throughput aptamer identification method to be used with the cell-SELEX technique to increase the aptamer selection rate against live cells. The feasibility of our approach is demonstrated by performing aptamer selection against a clear cell renal cell carcinoma (ccRCC) RCC-MF cell line using the RC-124 cell line from healthy kidney tissue for negative selection.
Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless
Authors: Jagtap Pravin Kumar Ankush , Müller Marisa , Masiewicz Pawel , von Bülow Sören , Hollmann Nele Merret , Simon Bernd , Thomae Andreas W. , Becker Peter B. , Hennig Janosch 
Published: November 2018

ABSTRACTMaleless (MLE) is an evolutionary conserved member of the DExH family of helicases in Drosophila. Besides its function in RNA editing and presumably siRNA processing, MLE is best known for its role in remodelling non-coding roX RNA in the context of X chromosome dosage compensation in male flies. MLE and its human orthologue, DHX9 contain two tandem double-stranded RNA binding domains (dsRBDs) located at the N-terminal region. The two dsRBDs are essential for localization of MLE at the X-territory and it is presumed that this involves binding roX secondary structures. However, for dsRBD1 roX RNA binding has so far not been described. Here, we determined the solution NMR structure of dsRBD1 and dsRBD2 of MLE in tandem and investigated its role in double-stranded RNA (dsRNA) binding. Our NMR data show that both dsRBDs act as independent structural modules in solution and are canonical, non-sequence-specific dsRBDs featuring non-canonical KKxAK RNA binding motifs. NMR titrations combined with filter binding experiments document the contribution of dsRBD1 to dsRNA binding in vitro. Curiously, dsRBD1 mutants in which dsRNA binding in vitro is strongly compromised do not affect roX2 RNA binding and MLE localization in cells. These data suggest alternative functions for dsRBD1 in vivo.