bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel Bayesian approach to predicting reductions in HIV incidence following increased testing interventions among gay, bisexual and other men who have sex with men in Vancouver, Canada
Authors: Irvine Michael A. , Konrad Bernhard P. , Michelow Warren , Balshaw Robert , Gilbert Mark , Coombs Daniel
Published: March 2018

Increasing HIV testing rates among high-risk groups should lead to increased numbers of cases being detected. Coupled with effective treatment and behavioural change among individuals with detected infection, increased testing should also reduce onward incidence of HIV in the population. However, it can be difficult to predict the strengths of these effects and thus the overall impact of testing. We construct a mathematical model of an ongoing HIV epidemic in a population of gay, bisexual and other men who have sex with men. The model incorporates different levels of infection risk, testing habits and awareness of HIV status among members of the population. We introduce a novel Bayesian analysis that is able to incorporate potentially unreliable sexual health survey data along with firm clinical diagnosis data. We parameterize the model using survey and diagnostic data drawn from a population of men in Vancouver, Canada. We predict that increasing testing frequency will yield a small-scale but long-term impact on the epidemic in terms of new infections averted, as well as a large short-term impact on numbers of detected cases. These effects are predicted to occur even when a testing intervention is short-lived. We show that a short-lived but intensive testing campaign can potentially produce many of the same benefits as a campaign that is less intensive but of longer duration.
An
in silico
model of cytotoxic T-lymphocyte activation in the lymph node following short peptide vaccination
Authors: Brown Liam V. , Gaffney Eamonn A. , Wagg Jonathan , Coles Mark C.
Published: March 2018

Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized,
in silico
, agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site. For peptides with MHC-I off-rates beyond this transition, it is predicted that no vaccination strategy will lead to successful expansion of CTLs. For slower off-rates, below the transition, the probability of CTL activation becomes sensitive to the numbers of DCs and T cells that interact subsequent to DC migration to the draining lymph node of the vaccination site. Thus, the off-rate is a key determinant of vaccine design.
Optic neuropathy and congenital glaucoma associated with probable Zika virus infection in Venezuelan patients
Authors: De Moraes C. Gustavo , Pettito Michele , Yepez Juan B. , Sakuntabhai Anavaj , Simon-Loriere Etienne , Zaidi Mussaret B. , Prot Matthieu , Ruffie Claude , Kim Susan S. , Allikmets Rando , Terwilliger Joseph D. , Lee Joseph H. , Maestre Gladys E.
Published: March 2018

Introduction. Although the current Zika virus (ZIKV) epidemic is a major public health concern, most reports have focused on congenital ZIKV syndrome, its most devastating manifestation. Severe ocular complications associated with ZIKV infections and possible pathogenetic factors are rarely described. Here, we describe three Venezuelan patients who developed severe ocular manifestations following ZIKV infections. We also analyse their serological response to ZIKV and dengue virus (DENV).

Case presentation. One adult with bilateral optic neuritis, a child of 4 years of age with retrobulbar uveitis and a newborn with bilateral congenital glaucoma had a recent history of an acute exanthematous infection consistent with ZIKV infection. The results of ELISA tests indicated that all patients were seropositive for ZIKV and four DENV serotypes.

Conclusion. Patients with ZIKV infection can develop severe ocular complications. Anti-DENV antibodies from previous infections could play a role in the pathogenesis of these complications. Well-designed epidemiological studies are urgently needed to measure the risk of ZIKV ocular complications and confirm whether they are associated with the presence of anti-flaviviral antibodies.
Ancient DNA analysis of food remains in human dental calculus from the Edo period, Japan
Authors: Sawafuji Rikai , Saso Aiko , Suda Wataru , Hattori Masahira , Ueda Shintaroh
Published: March 2018

Objectives: Although there are many methods for reconstructing diets of the past, detailed taxon identification is still challenging, and most plants hardly remain at a site. In this study, we applied DNA metabarcoding to dental calculus of Edo people for the taxonomic identification of food species.
Materials and Methods: DNA was extracted from 13 human dental calculi from the Unko-in site (18th-19th century) of the Edo period, Japan. Polymerase chain reaction (PCR) and sequencing were performed using a primer set specific to the genus Oryza, because rice (Oryza sativa) was a staple food and this was the only member of this genus present in Japan at that time. DNA metabarcoding targeting plants, animals (meat and fish), and fungi was also carried out to investigate dietary diversity.
Results: We detected amplified products of the genus Oryza from more than half of the samples using PCR and Sanger sequencing. DNA metabarcoding enabled us to identify taxa of plants and fungi, although taxa of animals were not detected, except human.
Discussion: Most of the plant taxonomic groups are present in Japan and include species consumed as food at that time, as confirmed by historical literature. The other groups featured in the lifestyle of Edo people, such as for medicinal purposes and tobacco. The results indicate that plant DNA analysis from calculus provides information about food diversity and lifestyle habits from the past and can complement other analytical methods such as starch analysis and stable isotope analysis.
Psychophysical reverse correlation reflects both sensory and decision-making processes
Authors: Okazawa Gouki , Sha Long , Purcell Braden A. , Kiani Roozbeh
Published: March 2018

Goal directed behavior depends on both sensory mechanisms that gather information from the outside world and decision-making mechanisms that select appropriate behavior based on that sensory information. Psychophysical reverse correlation is commonly used to quantify how fluctuations of sensory stimuli influence behavior and is generally believed to uncover the spatiotemporal weighting functions of sensory processes. Here we show that reverse correlations also reflect decision-making processes and can deviate significantly from the true sensory filters. Specifically, changes of decision bound and mechanisms of evidence integration systematically alter psychophysical reverse correlations. Similarly, trial-to-trial variability of sensory and motor delays and decision times causes systematic distortions in psychophysical kernels that should not be attributed to sensory mechanisms. We show that ignoring details of the decision-making process results in misinterpretation of reverse correlations, but proper use of these details turns reverse correlation into a powerful method for studying both sensory and decision-making mechanisms.
New tools for the analysis and validation of Cryo-EM maps and atomic models
Authors: Afonine Pavel V. , Klaholz Bruno P. , Moriarty Nigel W. , Poon Billy K. , Sobolev Oleg V. , Terwilliger Thomas C. , Adams Paul D. , Urzhumtsev Alexandre
Published: March 2018

Recent advances in the field of electron cryo-microscopy (cryo-EM) have resulted in a rapidly increasing number of atomic models of bio-macromolecules solved using this technique and deposited in the Protein Data Bank and the Electron Microscopy Data Bank. Similar to macromolecular crystallography, validation tools for these models and maps are required. While some of these validation tools may be borrowed from crystallography, new methods specifically for cryo-EM validation are required. We discuss new computational methods and tools implemented in Phenix, including d99 to estimate resolution, phenix.auto_sharpen to improve maps, and phenix.mtriage to analyze cryo-EM maps. We suggest that cryo-EM half-maps and masks are deposited to facilitate evaluation and validation of cryo-EM derived atomic models and maps. We also present the application of these tools to deposited cryo-EM atomic models and maps.
Pseudomonas aeruginosapartitioning protein ParB acts as a nucleoid-associated protein binding to multiple copies of aparS-related motif
Authors: Kawalek Adam , Bartosik Aneta Agnieszka , Glabski Krzysztof , Jagura-Burdzy Grazyna
Published: March 2018

ParA and ParB homologs are involved in accurate chromosome segregation in bacteria. ParBs participate in separation of ori domains by binding to specificparSsites, mainly localized close tooriC. InPseudomonas aeruginosaneither a lack ofparBgene nor modification of tenparSs is lethal. Remarkably, such mutants show not only defects in chromosome segregation but also growth retardation and motility dysfunctions. Moreover, a lack ofparBalters expression of over one thousand genes, suggesting that ParB could interact with the chromosome outside its canonicalparStargets.

Indeed, DNA immunoprecipitation with anti-ParB antibodies followed by deep sequencing (ChIP-seq) revealed 420 enriched regions in WT PAO1161 strain and around 1000 in a ParB-overproducing strain and in variousparSmutants. Vast majority of the ParB-enriched loci contained a heptanucleotide motif corresponding to one arm of theparSpalindrome. All previously postulatedparSsites with the exception ofparS5interacted with ParBin vivo.Whereas the ParB binding to the fourparSsites closest tooriC, parS1-4, is involved in chromosome segregation, its genome-wide interactions with hundreds ofparShalf-sites could affect chromosome topology, compaction and gene expression classifyingP. aeruginosaParB as a Nucleoid Associated Protein (NAP).
Exposing flaws in S-LDSC; reply to Gazal et al.
Authors: Speed Doug , Balding David J
Published: March 2018

In our recent publication,1 we examined the two heritability models most widely used when estimating SNP heritability: the GCTA Model, which is used by the software GCTA2 and upon which LD Score regression (LDSC) is based,3 and the LDAK Model, which is used by our software LDAK.4 First we demonstrated the importance of choosing an appropriate heritability model, by showing that estimates of SNP heritability can be highly sensitive to which model is assumed. Then we empirically tested the GCTA and LDAK Models on GWAS data for a wide variety of complex traits. We found that the LDAK Model fits real data both significantly and substantially better than the GCTA Model, indicating that LDAK estimates more accurately describe the genetic architecture of complex traits than those from GCTA or LDSC.

Some of our most striking results were our revised estimates of functional enrichments (the heritability enrichments of SNP categories defined by functional annotations). In general, estimates from LDAK were substantially more modest than previous estimates based on the GCTA Model. For example, we estimated that DNase I hypersensitive sites (DHS) were 1.4-fold (SD 0.1) enriched, whereas a study using GCTA had found they were 5.1-fold (SD 0.5) enriched,5 and we estimated that conserved SNPs were 1.3-fold (SD 0.3) enriched, whereas a study using S-LDSC (stratified LDSC) had found they were 13.3-fold (SD 1.5) enriched.6

In their correspondence, Gazal et al. dispute our findings. They assert that the heritability model assumed by LDSC is more realistic than the LDAK Model, and that estimates of enrichment from S-LDSC7 are more accurate than those from LDAK. Here, we explain why their justification for preferring the model used by LDSC is incorrect, and provide a simple demonstration that S-LDSC produces unreliable estimates of enrichment.
Reproducible integration of multiple sequencing datasets to form high-confidence SNP, indel, and reference calls for five human genome reference materials
Authors: Zook Justin M. , McDaniel Jennifer , Parikh Hemang , Heaton Haynes , Irvine Sean A. , Trigg Len , Truty Rebecca , McLean Cory Y. , De La Vega Francisco M. , Xiao Chunlin , Sherry Stephen , Salit Marc
Published: March 2018

Benchmark small variant calls from the Genome in a Bottle Consortium (GIAB) for the CEPH/HapMap genome NA12878 (HG001) have been used extensively for developing, optimizing, and demonstrating performance of sequencing and bioinformatics methods. Here, we develop a reproducible, cloud-based pipeline to integrate multiple sequencing datasets and form benchmark calls, enabling application to arbitrary human genomes. We use these reproducible methods to form high-confidence calls with respect to GRCh37 and GRCh38 for HG001 and 4 additional broadly-consented genomes from the Personal Genome Project that are available as NIST Reference Materials. These new genomes’ broad, open consent with few restrictions on availability of samples and data is enabling a uniquely diverse array of applications. Our new methods produce 17% more high-confidence SNPs, 176% more indels, and 12% larger regions than our previously published calls. To demonstrate that these calls can be used for accurate benchmarking, we compare other high-quality callsets to ours (e.g., Illumina Platinum Genomes), and we demonstrate that the majority of discordant calls are errors in the other callsets, We also highlight challenges in interpreting performance metrics when benchmarking against imperfect high-confidence calls. We show that benchmarking tools from the Global Alliance for Genomics and Health can be used with our calls to stratify performance metrics by variant type and genome context and elucidate strengths and weaknesses of a method.
Encoding the expectation of a sensory stimulus
Authors: Zhang Lijun , Chen Alex , Saha Debajit , Li Chao , Raman Baranidharan
Published: March 2018

Most organisms possess an ability to differentiate unexpected or surprising sensory stimuli from those that are repeatedly encountered. How is this sensory computation performed? We examined this issue in the locust olfactory system. We found that odor-evoked responses in the antennal lobe (downstream to sensory neurons) systematically reduced upon repeated encounters of a temporally discontinuous stimulus. Rather than confounding information about stimulus identity and intensity, neural representations were optimized to encode equivalent stimulus-specific information with fewer spikes. Further, spontaneous activity of the antennal lobe network also changed systematically and became negatively correlated with the response elicited by the repetitive stimulus (i.e. ‘a negative image’). Notably, while response to the repetitive stimulus reduced, exposure to an unexpected/deviant cue generated undamped and even exaggerated spiking responses in several neurons. In sum, our results reveal how expectation regarding a stimulus is encoded in a neural circuit to allow response optimization and preferential filtering.
Neurofilament light as a blood biomarker for neurodegeneration in Down syndrome
Authors: Strydom Andre , Heslegrave Amanda , Startin Carla M , Mok Kin Y , Hardy John , Groet Jurgen , Nizetic Dean , Zetterberg Henrik ,   And The LonDownS Consortium
Published: March 2018

INTRODUCTION

Down syndrome (DS) may be considered a genetic form of Alzheimer’s disease (AD) due to universal development of AD neuropathology, but diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. A potential biomarker is neurofilament light (NF-L), due to its association with axonal damage in neurodegenerative conditions.

METHODS

We measured blood NF-L concentration in 100 adults with DS using Simoa NF-light® assays, and examined relationships with age, and cross-sectional and longitudinal dementia diagnosis.

RESULTS

NF-L levels increased with age (Spearman’s rho = 0.789, p<0.001), with a steep increase after age 40, and were predictive of dementia status (p=0.022 adjusting for age, sex, and APOE4) but showed no relationship with longstanding epilepsy or premorbid ability. Baseline NF-L levels were associated with longitudinal dementia status.

DISCUSSION

NF-L is a biomarker for neurodegeneration in DS, with potential for use in future clinical trials to prevent or delay dementia.

Research in context

Systematic review

The authors reviewed the literature using PubMed searches supplemented with our knowledge of pending papers in this research area. While blood NF-L has been associated with clinical features of progression in a number of neurodegenerative conditions, we have not identified any reports of NF-L associated with cognitive decline in DS, a genetic form of AD.

Interpretation

Our findings demonstrate the potential utility of NF-L as a blood biomarker of neurodegeneration in DS, a population that may not be able to tolerate more invasive procedures such as neuroimaging and lumbar punctures to track progression.

Future directions

The association between NF-L and other markers of longitudinal AD progression should be explored further in future work.
Model-based analysis of the stiffness of the wrist joint in active and passive conditions
Authors: Zonnino Andrea , Sergi Fabrizio
Published: March 2018

The control of joint stiffness is a fundamental mechanism used to control human movements. While many studies have observed how stiffness is controlled for tasks involving shoulder and elbow motion, a limited amount of knowledge is available for wrist movements, though the wrist plays a crucial role in fine manipulation.

We have developed a computational framework based on a realistic musculoskeletal model, which allows to calculate the passive and active components of the wrist joint stiffness. We first used the framework to validate the musculoskeletal model against experimental measurements of the passive wrist joint stiffness, and then to study the contribution of different muscle groups on the passive joint stiffness. We finally used the framework to study the effect of muscle co - contraction on the active joint stiffness.

The results show that thumb and finger muscles play a crucial role in determining the passive wrist joint stiff - ness: in the neutral posture, the direction of maximum stiffness aligns with the experimental measurements, and the magnitude increases by 113% when they are included. Moreover, the analysis of the controllability of joint stiffness showed that muscle co - contraction positively correlates with the stiffness magnitude and negatively correlates with the variability of the stiffness orientation (p < 0.01 in both cases). Finally, an exhaustive search showed that with appropriate selection of a muscle activation strategy, the joint stiffness orientation can be arbitrarily modulated. This observation suggests the absence of biomechanical constraints on the controllability of the orientation of the wrist joint stiffness.
Limited uptake of essential amino acid is effective for cancer therapy in metabolic networks of integrated constraint-based models
Authors: Tamura Takeyuki
Published: March 2018

Nam models are context-specific genome-scale metabolic models for nine types of cancer and corresponding normal cells reconstructed from RECON 2, genetic mutation information, and expression profile data. In this study, computational experiments were conducted using Nam models to find effective ratios of uptake reactions such that cancer cells do not grow while normal cells grow. The original Nam models were extended to consider interactions between cancer and normal cells using an approach developed for representing host-microbe interactions. When uptake ratio of only single reaction was allowed to change at a time, the results of computational experiments showed that every essential amino acid had effective ranges for almost all nine types of cancer, while the other uptake reactions rarely had such effective ranges.
Landscape-level DNA metabarcoding study in the Pannonian forests reveals differential effects of slope aspect on taxonomic and functional groups of fungi
Authors: Geml József
Published: March 2018

In temperate regions, slope aspect is one of the most influential drivers of environmental conditions at landscape level. The effect of aspect on vegetation has been well studied, but virtually nothing is known about how fungal communities are shaped by aspect-driven environmental conditions. I carried out DNA metabarcoding of fungi from soil samples taken in a selected study area of Pannonian forests to compare richness and community composition of taxonomic and functional groups of fungi between slopes of predominantly southerly vs. northerly aspect and to assess the influence of selected environmental variables on fungal community composition. The deep sequence data presented here (i.e. 980 766 quality-filtered sequences) indicate that both niche (environmental filtering) and neutral (stochastic) processes shape fungal community composition at landscape level. Fungal community composition correlated strongly with aspect, with many fungi showing preference for either south-facing or north-facing slopes. Several taxonomic and functional groups showed significant differences in richness between north-and south-facing slopes and strong compositional differences were observed in all functional groups. The effect of aspect on fungal communities likely is mediated through contrasting mesoclimatic conditions, that in turn influence edaphic processes as well as vegetation. Finally, the data presented here provide an unprecedented insight into the diversity and landscape-level community dynamics of fungi in the Pannonian forests.
Radioprotective role of cyanobacterial phycobilisomes
Authors: Klementiev Konstantin E. , Maksimov Eugene G. , Gvozdev Danil A. , Tsoraev Georgy V. , Protopopov Fedor F. , Elanskaya Irina V. , Abramov Sergey M. , Dyakov Maksim Yu. , Ilyin Vyacheslav K. , Nikolaeva Nadezhda A. , Slonimskiy Yury B. , Sluchanko Nikolai N. , Lebedev Victor M. , Spassky Andrew V. , Friedrich Thomas , Maksimov Georgy V. , Paschenko Vladimir Z. , Rubin Andrew B.
Published: March 2018

It is now generally accepted that cyanobacteria are responsible for production of oxygen, which led to the so-called “Great Oxygenation Event”. Appearance of dioxygen in Earth’s atmosphere resulted in formation of the ozone layer and the ionosphere, which caused significant reduction of ionizing radiation levels at the surface of our planet. This event not only increased biological diversity but also canceled the urgency of previously developed mechanisms of DNA protection, which allowed to survive and develop in harsh environmental conditions including exposure to cosmic rays. In order to test the hypothesis if one of the oldest organisms on Earth retained ancient protection mechanisms, we studied the effect of ionizing radiation (IoR, here: α-particles with a kinetic energy of about 30 MeV) and space flight during the mission of the Foton-M4 satellite on cells of Synechocystis sp. PCC6803. By analyzing spectral and functional characteristics of photosynthetic membranes we revealed numerous similarities between cells exposed to IoR and after the space mission. In both cases, we found that excitation energy transfer from phycobilisomes to photosystems was interrupted and the concentration of phycobiliproteins was significantly reduced. Although photosynthetic activity was severely suppressed, the effect was reversible and the cells were able to rapidly recover from stress under normal conditions. Moreover, in vitro experiments demonstrated that the effect of IoR on isolated phycobilisomes was completely different from such in vivo. These observations suggest that the actual existence and the uncoupling of phycobilisomes under irradiation stress could play specific role not only in photo-, but also in radioprotection, which was crucial for early stages of evolution and the development of Life on Earth.
Effect of buspirone on the H-reflex in acute spinal decerebrated mice
Authors: Develle Yann , Leblond Hugues
Published: March 2018

Pharmacological treatment facilitating locomotor expression also modulates reflex expression through the re-arrangement of spinal networks. Buspirone, a partial serotonin receptor agonist (5-HT1A), was recently shown to facilitate and even trigger locomotor movements in mice after complete spinal lesion (Tx). Here, we studied its effect on the H-reflex after acute Tx in adult mice. To avoid possible impacts of anesthetics on H-reflex depression, experiments were performed after decerebration in un-anesthetized mice (N=13). The H-reflex in plantar muscles of the hind-paw was recorded after tibial nerve stimulation 2 h after Tx at the 8ththoracic vertebrae. Average H/M ratio was compared before and every 10 min after buspirone (8 mg/kg, i.p.) for 60 min. Frequency-dependent depression (FDD) of the H-reflex was assessed before and 50 min after buspirone. Before buspirone, a stable H-reflex could be elicited in acute spinal mice and FDD of the H-reflex was observed at 5Hz (68%) and 10Hz (70%) relative to 0.2Hz. After buspirone, the H/M ratio was initially significantly decreased to 69% of pre-treatment. It then increased significantly 30 to 60 min after exposure to buspirone, reaching 170% 60 min after injection. FDD 50 min after buspirone was not significantly different that FDD without treatment. Altogether results suggest that the reported pro-locomotor effect of buspirone occurs at a time where there is a reflex depression followed by a second phase marked by enhancement of reflex excitability, denoting functional inhibitory control.

KEY POINTS SUMMARY

Buspirone, a partial serotoninergic agonist (5HT1A), exerts a considerable acute facilitation of spinally-mediated locomotion after a complete spinal lesion in mice.

Since locomotion is associated with reflex modulation, we focused in this study on the effect of buspirone on H-reflex in acute spinal mice after decerebration and removal of anesthesia.

Buspirone injection resulted in a depression of the H-reflex during the first 20 minutes followed, 40 minutes later, by an increase of the reflex.

The H-reflex increase is not due to a disinhibition since buspirone had no effect on the frequency dependent depression (FDD) of the H-reflex.

The use of a model of adult decerebrate mouse with complete spinal cord injury allows to establish that buspirone has a biphasic effect on the H-reflex and that the inhibitory action on sensory information concurs with an excitatory action on locomotion.

Abbreviations

5-HT

5-Hydroxytryptamine

5-HT1A

1A subunit in 5-Hydroxytryptamine receptor

8-OHDPAT

8-Hydroxy-2-DI-n-Propylamino-Tetraline CPG Central Pattern Generator

EMG

electromyographic

FDD

Frequency Dependent Depression

GABA

Gamma-Aminobutyric-Acid TASK-1 acid-sensitiv-K-1

Tx

complete transection
Epithelial micro-invasion byStreptococcus pneumoniaeinduces epithelial-derived innate immunity during colonisation at the human mucosal surface
Authors: Weight Caroline M , Venturini Cristina , Pojar Sherin , Jochems Simon P. , Reiné Jesús , Nikolaou Elissavet , Solórzano Carla , Noursadeghi Mahdad , Brown Jeremy S , Ferreira Daniela M. , Heyderman Robert S
Published: March 2018

Control ofStreptococcus pneumoniaecolonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Using an Experimental Human Pneumococcal Carriage Model (EHPC), we show thatS. pneumoniaecolonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epitheliumin vitroshaped the host transcriptomic response. Using epithelial modules from a human epithelial cell model that recapitulates ourin vivofindings, comprising of innate signalling/ regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. These results show that rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances the inflammatory/ innate immune response associated with clearance.
An Open-source Tool for Analysis and Automatic Identification of Dendritic Spines Using Machine Learning
Authors: Smirnov Michael S , Garrett Tavita R , Yasuda Ryohei
Published: March 2018

Synaptic plasticity, the cellular basis for learning and memory, is mediated by a complex biochemical network of signaling proteins. These proteins are compartmentalized in dendritic spines, the tiny, bulbous, post-synaptic structures found on neuronal dendrites. The ability to screen a high number of molecular targets for their effect on dendritic spine structural plasticity will require a high-throughput imaging system capable of stimulating and monitoring hundreds of dendritic spines in various conditions. For this purpose, we present a program capable of automatically identifying dendritic spines in live, fluorescent tissue. Our software relies on a machine learning approach to minimize any need for parameter tuning from the user. Custom thresholding and binarization functions serve to “clean” fluorescent images, and a neural network is trained using features based on the relative shape of the spine perimeter and its corresponding dendritic backbone. Our algorithm is rapid, flexible, has over 90% accuracy in spine detection, and bundled with our user-friendly, open-source, MATLAB-based software package for spine analysis.
Multimodal modeling of neural network activity: computing LFP, ECoG, EEG and MEG signals with LFPy2.0
Authors: Hagen Espen , Næss Solveig , Ness Torbjørn V. , Einevoll Gaute T.
Published: March 2018

Recordings of extracellular electrical, and later also magnetic, brain signals have been the dominant technique for measuring brain activity for decades. The interpretation of such signals is however nontrivial, as the measured signals result from both local and distant neuronal activity. In volume-conductor theory the extracellular potentials can be calculated from a distance-weighted sum of contributions from transmembrane currents of neurons. Given the same transmembrane currents, the contributions to the magnetic field recorded both inside and outside the brain can also be computed. This allows for the development of computational tools implementing forward models grounded in the biophysics underlying electrical and magnetic measurement modalities.

LFPy (LFPy.readthedocs.io) incorporated a well-established scheme for predicting extracellular potentials of individual neurons with arbitrary levels of biological detail. It relies on NEURON (neuron.yale.edu) to compute transmembrane currents of multicompartment neurons which is then used in combination with an electrostatic forward model. Its functionality is now extended to allow for modeling of networks of multicompartment neurons with concurrent calculations of extracellular potentials and current dipole moments. The current dipole moments are then, in combination with suitable volume-conductor head models, used to compute non-invasive measures of neuronal activity, like scalp potentials (electroencephalographic recordings; EEG) and magnetic fields outside the head (magnetoencephalographic recordings; MEG). One such built-in head model is the four-sphere head model incorporating the different electric conductivities of brain, cerebrospinal fluid, skull and scalp.

We demonstrate the new functionality of the software by constructing a network of biophysically detailed multicompartment neuron models from the Neocortical Microcircuit Collaboration (NMC) Portal (bbp.epfl.ch/nmc-portal) with corresponding statistics of connections and synapses, and computein vivo-like extracellular potentials (local field potentials, LFP; electrocorticographical signals, ECoG) and corresponding current dipole moments. From the current dipole moments we estimate corresponding EEG and MEG signals using the four-sphere head model. We also show strong scaling performance of LFPy with different numbers of message-passing interface (MPI) processes, and for different network sizes with different density of connections.

The open-source software LFPy is equally suitable for execution on laptops and in parallel on high-performance computing (HPC) facilities and is publicly available onGitHub.com.
Data-theoretical Synthesis of the Early Developmental Process
Authors: Alicea Bradly , Gordon Richard , Portegys Thomas E.
Published: March 2018

Biological development is often described as a dynamic, emergent process. This is evident across a variety of phenomena, from the temporal organization of cell types in the embryo to compounding trends that affect large-scale differentiation. To better understand this, we propose combining quantitative investigations of biological development with theory-building techniques. This provides an alternative to the gene-centric view of development: namely, the view that developmental genes and their expression determine the complexity of the developmental phenotype. Using the model systemCaenorhabditis elegans, we examine time-dependent properties of the embryonic phenotype and utilize the unique life-history properties to demonstrate how these emergent properties can be linked together by data analysis and theory-building. We also focus on embryogenetic differentiation processes, and how terminally-differentiated cells contribute to structure and function of the adult phenotype. Examining embryogenetic dynamics from 200 to 400 minutes post-fertilization provides basic quantitative information on developmental tempo and process. To summarize, theory construction techniques are summarized and proposed as a way to rigorously interpret our data. Our proposed approach to a formal data representation that can provide critical links across life-history, anatomy and function.
Association of whole-genome and NETRIN1 signaling pathway-derived polygenic risk scores for Major Depressive Disorder and thalamic radiation white matter microstructure in UK Biobank
Authors: Barbu Miruna C. , Zeng Yanni , Shen Xueyi , Cox Simon R. , Clarke Toni-Kim , Gibson Jude , Adams Mark J. , Johnstone Mandy , Haley Chris S. , Lawrie Stephen M. , Deary Ian J. ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium,   23andMe Research Team, McIntosh Andrew M. , Whalley Heather C.
Published: March 2018

Background

Major Depressive Disorder (MDD) is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome, and growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide an important route for identification of disease mechanisms by focusing on a specific process excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether MDD polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRS) and the whole genome excluding NETRIN1 pathway genes (genomic-PRS) were associated with white matter integrity.

Methods

We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: N = 6,401; MD: N = 6,390).

Results

We found significantly lower FA in the superior longitudinal fasciculus (β = -0.035, pcorrected = 0.029) and significantly higher MD in a global measure of thalamic radiations (β = 0.029, pcorrected = 0.021), as well as higher MD in the superior (β = 0.034, pcorrected = 0.039) and inferior (β = 0.029, pcorrected = 0.043) longitudinal fasciculus and in the anterior (β = 0.025, pcorrected = 0.046) and superior (β = 0.027, pcorrected = 0.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.

Conclusions

Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for MDD through effects on thalamic radiation white matter microstructure.
The mitochondrial genomes of the mesozoansIntoshia linei, Dicyemasp., andDicyema japonicum
Authors: Robertson Helen. E. , Schiffer Philipp. H. , Telford Maximilian. J.
Published: March 2018

The Dicyemida and Orthonectida are two groups of tiny, simple, vermiform parasites that have historically been united in a group named the Mesozoa. Both Dicyemida and Orthonectida have just two cell layers and appear to lack any defined tissues. They were initially thought to be evolutionary intermediates between protozoans and metazoans but more recent analyses indicate that they are protostomian metazoans that have undergone secondary simplification from a complex ancestor. Here we describe the first almost complete mitochondrial genome sequence from an orthonectid,Intoshia linei, and describe nine and eight mitochondrial protein-coding genes fromDicyemasp. andDicyema japonicum, respectively. The 14,247 base pair longI. lineisequence has typical metazoan gene content, but is exceptionally AT-rich, and has a divergent gene order compared to other metazoans. The data we present from the Dicyemida provide very limited support for the suggestion that dicyemid mitochondrial genes are found on discrete mini-circles, as opposed to the large circular mitochondrial genomes that are typical across the Metazoa. Thecox1gene from dicyemid species has a series of conserved in-frame deletions that is unique to this lineage. Usingcox1genes from across the genusDicyema, we report the first internal phylogeny of this group.

Key Findings

We report the first almost-complete mitochondrial genome from an orthonectid parasite,Intoshia linei, including 12 protein-coding genes; 20 tRNAs and putative sequences for large and small subunit rRNAs. We find that theI. lineimitochondrial genome is exceptionally AT-rich and has a novel gene order compared to other published metazoan mitochondrial genomes. These findings are indicative of the rapid rate of evolution that has occurred in theI. lineimitochondrial genome.

We also report nine and eight protein-coding genes, respectively, from the dicyemid speciesDicyemasp. andDicyema japonicum, and use thecox1genes from both species for phylogenetic inference of the internal phylogeny of the dicyemids.

We find that thecox1gene from dicyemids has a series of four conserved in-frame deletions which appear to be unique to this group.
Genetic dissection of assortative mating behavior
Authors: Merrill Richard M. , Rastas Pasi , Melo Maria C. , Barker Sarah , Davey John , McMillan W. Owen , Jiggins Chris D.
Published: March 2018

The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution, or more generally about the genetic basis for assortative mating behaviors. The warning patterns ofHeliconius melpomeneandH. cydnoare under disruptive selection due to increased predation of non-mimetic hybrids, and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. Three QTLs each explain a large proportion of the differences in preference behavior observed between the parental species. Two of these QTLs are on chromosomes with major color pattern genes, including one that is tightly associated with the geneoptix. Different loci influence different aspects of attraction, suggesting that behavioral isolation inHeliconiusinvolves the evolution of independently segregating modules, similar to those for the corresponding wing pattern cues. Hybridization and subsequent sharing of wing pattern loci has played an important role during adaptation and speciation inHeliconiusbutterflies. The existence of large effect preference loci could similarly assist the evolution of novel behavioral phenotypes through recombination and introgression, and should facilitate rapid speciation.
Disentangling locus of perceptual learning in the visual hierarchy of motion processing
Authors: Zhang Ruyuan , Tadin Duje
Published: March 2018

Visual perceptual learning (VPL) can lead to long-lasting perceptual improvements. While the efficacy of VPL is well established, there is still a considerable debate about what mechanisms underlie the effects of VPL. Much of this debate concentrates on where along the visual processing hierarchy behaviorally relevant plasticity takes place. Here, we aimed to tackle this question in context of motion processing, a domain where links between behavior and processing hierarchy are well established. Specifically, we took advantage of an established transition from component-dependent representations at the earliest level to pattern-dependent representations at the middle-level of cortical motion processing. We trained two groups of participants on the same motion direction identification task using either grating or plaid stimuli. A set of pre- and post-training tests was used to determine the degree of learning specificity and generalizability. This approach allowed us to disentangle contributions from both low- and mid-level motion processing, as well as high-level cognitive changes. We observed a complete bi-directional transfer of learning between component and pattern stimuli as long as they shared the same apparent motion direction. This result indicates learning-induced plasticity at intermediate levels of motion processing. Moreover, we found that motion VPL is specific to the trained stimulus direction, speed, size, and contrast, highlighting the pivotal role of basic visual features in VPL, and diminishing the possibility of non-sensory decision-level enhancements. Taken together, our study psychophysically examined a variety of factors mediating motion VPL, and demonstrated that motion VPL most likely alters visual computation in the middle stage of motion processing.
Can we study 3D grid codes non-invasively in the human brain? Methodological considerations and fMRI findings
Authors: Kim Misun , Maguire Eleanor A.
Published: March 2018

Recent human functional magnetic resonance imaging (fMRI) and animal electrophysiology studies suggest that grid cells in entorhinal cortex are an efficient neural mechanism for encoding knowledge about the world, not only for spatial location but also for more abstract cognitive information. The world, be it physical or abstract, is often high-dimensional, but grid cells have been mainly studied on a simple two-dimensional (2D) plane. Recent theoretical studies have proposed how grid cells encode three-dimensional (3D) physical space, but it is unknown whether grid codes can be examined non-invasively in humans. Here, we investigated whether it was feasible to test different 3D grid models using fMRI based on the direction-modulated property of grid signals. In doing so, we developed interactive software to help researchers visualize 3D grid fields and predict grid activity in 3D as a function of movement directions. We found that a direction-modulated grid analysis was sensitive to one type of 3D grid model – a face-centred cubic (FCC) lattice model. As a proof of concept, we searched for 3D grid-like signals in human entorhinal cortex using a novel 3D virtual reality paradigm and a new fMRI analysis method. We found that signals in the left entorhinal cortex were explained by the FCC model. This is preliminary evidence for 3D grid codes in the human brain, notwithstanding the inherent methodological limitations of fMRI. We believe that our findings and software serve as a useful initial stepping-stone for studying grid cells in realistic 3D worlds and also, potentially, for interrogating abstract high-dimensional cognitive processes.

Highlights

We present software and an analysis method to probe 3D grid codes using human fMRI Based on an alignment score between 3D movement direction and grid orientation We then tested this using a 3D virtual environment and fMRI

Signals in entorhinal cortex were explained by a face-centred cubic lattice model
Quantifying the impact of public omics data
Authors: Perez-Riverol Yasset , Zorin Andrey , Dass Gaurhari , Glont Mihai , Vizcaíno Juan Antonio , Jarnuczak Andrew F. , Petryszak Robert , Ping Peipei , Hermjakob Henning
Published: March 2018

The amount of omics data in the public domain is increasing every year [1, 2]. Public availability of datasets is growing in all disciplines, because it is considered to be a good scientific practice (e.g. to enable reproducibility), and/or it is mandated by funding agencies, scientific journals, etc. Science is now a data intensive discipline and therefore, new and innovative ways for data management, data sharing, and for discovering novel datasets are increasingly required [3, 4]. However, as data volumes grow, quantifying its impact becomes more and more important. In this context, the FAIR (Findable, Accessible, Interoperable, Reusable) principles have been developed to promote good scientific practises for scientific data and data resources [5]. In fact, recently, several resources [1, 2, 6] have been created to facilitate the Findability (F) and Accessibility (A) of biomedical datasets. These principles put a specific emphasis on enhancing the ability of both individuals and software to discover and re-use digital objects in an automated fashion throughout their entire life cycle [5]. While data resources typically assign an equal relevance to all datasets (e.g. as results of a query), the usage patterns of the data can vary enormously, similarly to other “research products” such as publications. How do we know which datasets are getting more attention? More generally, how can we quantify the scientific impact of datasets?
Jeans knowledge base development based on sensory evaluation technology for customers’ personalized recommendation
Authors: Zhang Junjie , Zeng Xianyi , Liu Kaixuan , Yan Hong , Dong Min
Published: March 2018

Purpose

The purpose of this paper is to set up a women’s jeans knowledge base between consumer profile and jeans profile. The result of study could be applied to jeans recommendation system for a special consumer.

Design/methodology/approach

Women’s jeans are chosen as research objects. The sensory evaluation technology and intelligent data fusion methods are applied in this research.

Findings

Eight pairs of words were selected to set up normalized sensory evaluation criteria in the study for describing both consumers’ expectations and products. The relation between consumer profile and jeans profile could be quantified according to the principle of sensory evaluation technology.

Practical implications

Four experiments are designed for setting up this knowledge base by sensory evaluation technology, and set up the women’s jeans knowledge base by intelligent data fusion methods.

Originality/value

The theory of sensory evaluation technology is applied for building women’s jeans knowledge base that can be used for consumer-oriented intelligent garment recommendation system.