bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigation-Assisted Nasal Bone Osteotomy for Malunited Fracture
Authors: Ogino Akihiro , Onishi Kiyoshi , Nakamichi Miho , Okaneya Tetsuya
Published: November 2017

Background:

Nasal bone osteotomy subjectively judges the position for osteotomy by visual inspection and by manual feel using the fingertip. Therefore, the outcome depends on the surgeon's experience and mastery of the procedure is technically challenging.

Methods:

The authors applied a navigation system for the intraoperative evaluation of the osteotomy line and reduction position in 5 patients with malunited nasal bone fracture. The authors performed the operation with a temporal bone post developed for otologic surgery using Stealth Station S7 System (Medtronic, Minneapolis, MN). The suretrack is attached to the bone chisel. The authors performed the osteotomies while visualizing the tip of the chisel on the monitor.

In addition, evaluation of the reduction position was performed by insertion of a 23G needle syringe with the suretrack to the nasal bone surface.

Results:

The tip of the bone chisel was visible on the monitor, and the authors could perform osteotomies while confirming the position and direction of osteotomy. In addition, the reduction position could be visualized clearly on the monitor.

Conclusion:

Navigation systems can confirm the 3-dimensional spatial relationship around the fracture site in real time, requiring only comparatively simple preoperative preparation and intraoperative operation without radiation exposure. Therefore, the advantage is that even an inexperienced surgeon can perform an accurate evaluation. This would be useful as a guide for young doctors and medical students as it would be possible to perform safe and accurate osteotomy for old nasal bone fractures.
Evaluating of Platelet-Rich Fibrin in the Treatment of Alveolar Cleft With Iliac Bone Graft By Means of Volumetric Analysis
Authors: Saruhan Nesrin , Ertas Umit
Published: November 2017

The purpose of this study was to evaluate the efficiency of platelet-rich fibrin usage in the treatment of alveolar cleft with iliac bone graft by means of volumetric analysis. In this study, 22 patients with alveolar clefts—including 13 unilateral and 9 bilateral—were treated with anterior iliac crest bone grafts. Patients were divided into 2 groups as control (group A) and platelet-rich fibrin (group B) groups. Cone beam computed tomography (CBCT) scans were obtained preoperatively and 6 months postoperatively. Three-dimensional reconstructions of CBCT images were created by using Mimics software. Preoperative alveolar cleft volume and postoperative newly formed bone volume were assessed volumetrically. The percentages of preoperative alveolar cleft volume ranged from 0.51 to 2.04 cm3, with a mean volume of 0.98 ± 0.33 cm3. The percentages of newly formed bone in group B ranged from 50.70% to 80.09%, with a mean percentage of 68.21 ± 10.80%. In Group A, the percentages of bone formation ranged from 47.02% to 79.23%, with a mean percentage of 64.62 ± 9.49%. Platelet-rich fibrin can be used in the treatment of alveolar cleft with corticocancellous bone graft harvested from the anterior iliac crest, but in this study, there was no statistically significant difference between the groups for postoperative newly formed bone volume (P > 0.05).
Perftoran (Vidaphor)—Introduction to Western Medicine
Authors: Latson Gary W.
Published: November 2017

Perftoran, which has been rebranded as Vidaphor for marketing in North America, is an emulsion of perfluorocarbons in a surfactant and electrolyte mixture. It was developed in Russia as an oxygen-carrying intravenous plasma additive for hemorrhagic anemia and ischemic conditions from various etiologies. It was approved for clinical use in Russia in 1996 and used by the Russian Armed Forces and in civilian medical care. It was also approved in Mexico from 2005 to 2010. It has been reportedly administered to over 35,000 patients with significant evidence of benefit and relatively mild and manageable adverse effects. It may have significant potential for use in hemorrhagic shock if human red blood cells are not available, and for several other applications including treatment of vascular gas embolism, cerebral or spinal trauma, and regional ischemia. It is different from other perfluorocarbon preparations under development in the United States in that it uses a different primary perfluorocarbon (perfluorodecalin) and a surfactant (Proxanol 268) instead of egg-yok phospholipid as the emulsion vehicle. Perftoran has a much smaller particle size resulting in milder adverse effects. It has been safely administered to more patients than any oxygen carrier currently under development. A newly formed United States Corporation (FluorO2 Therapeutics, Inc.) intends to manufacture the product in the United States under GMP standards and make it available for clinical use in Mexico and Latin America and pursue research to support eventual approval in the United States for human and veterinary use. This article will briefly review key information about this product and provide references for the interested reader.
Laboratory examinations for the vestibular system
Authors: van de Berg Raymond , Rosengren Sally , Kingma Herman
Published: November 2017

Purpose of review

In the last decades, researchers suggested that clinical assessment of labyrinthine function in detail became easy thanks to video head impulse tests (VHITs), vestibular evoked myogenic potential test (VEMP) and video-oculography (VOG). It has been argued that they can replace electronystagmography, the caloric and rotatory chair tests. This review addresses the latest evaluations of these tests and the opportunities they offer, but also the limitations in clinical practice.

Recent findings

The VHIT and suppression head impulse test (SHIMP) are under ideal circumstances able to accurately identify deficits of the VOR in 3D. However, in a relevant part of the patient population, pupil tracking is inaccurate, video-goggles slip and VOR quantification is problematic. The dissociation between the VHIT and caloric test suggests that these tests are complementary. A new 3D-VOG technique claims to quantify eye torsion better than before, opening multiple diagnostic possibilities. VEMPs remain difficult to standardize. Variability in normal cervical vestibular-evoked myogenic potential amplitude is large. VEMPs become smaller or absent with age, raising questions of whether there is a lower normal limit at all. Recent research shows that the labyrinth is directly stimulated in the MRI offering new opportunities for diagnostics and research.

In clinical practice, the VHIT, SHIMP, VEMP and new 3D-VOG techniques improve diagnostic power. Unfortunately, technical issues or variability prevent reliable quantitative evaluation in a part of the regular patient population. The traditional caloric and rotatory chair test can still be considered as valuable complementary tests.
Role for extracellular vesicles in the tumour microenvironment
Authors: O'Loghlen Ana
Published: November 2017

Extracellular vesicles (EVs) are small-membrane vesicles secreted by most cells types with the role to provide intercellular communication both locally and systemically. The transfer of their content between cells, which includes nucleic acids, proteins and lipids, confers the means for these interactions and induces significant cellular behaviour changes in the receiving cell. EVs are implicated in the regulation of numerous physiological and pathological processes, including development and neurological and cardiovascular diseases. Importantly, it has been shown that EV signalling is essential in almost all the steps necessary for the progress of carcinomas, from primary tumours to metastasis. In this review, we will focus on the latest findings for EV biology in relation to cancer progression and the tumour microenvironment.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Interplay of target site architecture and miRNA abundance determine miRNA activity and specificity
Authors: Brancati Giovanna , Carl Sarah H. , Großhans Helge
Published: November 2017

The recognition that the miRNA seed sequence is a major determinant of miRNA activity has greatly advanced the ability to predict miRNA targets. However, it has remained unclear to what extent miRNAs act redundantly when they are members of the same family and thus share a common seed. Using in vivo studies in C. elegans, we uncover features that drive specific target repression by individual miRNA family members. We find that seed-distal complementarity to a specific family member promotes specificity. However, the extent and robustness of specificity are greatly increased by seed match ‘imperfections’, such as bulges and G:U wobble base pairs. Depending on the seed match architecture, specificity may be overcome by increasing the levels of a miRNA lacking seed-distal complementarity. Hence, in contrast to a binary distinction between functional and non-functional target sites, our data support a model where functionality depends on a combination of target site quality and miRNA abundance. This emphasizes the importance of studying miRNAs under physiological conditions in their endogenous contexts.
Eye movement-related confounds in neural decoding of visual working memory representations
Authors: Mostert Pim , Albers Anke Marit , Brinkman Loek , Todorova Larisa , Kok Peter , de Lange Floris P.
Published: November 2017

The study of visual working memory (VWM) has recently seen revitalization with the emergence of new insights and theories regarding its neural underpinnings. One crucial ingredient responsible for this progress is the rise of neural decoding techniques. These techniques promise to uncover the representational contents of neural signals, as well as the underlying code and the dynamic profile thereof. Here, we aimed to contribute to the field by subjecting human volunteers to a combined VWM/imagery task, while recording and decoding their neural signals as measured by MEG. At first sight, the results seem to provide evidence for a persistent, stable representation of the memorandum throughout the delay period. However, control analyses revealed that these findings can be explained by subtle, VWM-specific eye movements. As a potential remedy, we demonstrate the use of a functional localizer, which was specifically designed to target bottom-up sensory signals and as such avoids eye movements, to train the neural decoders. This analysis revealed a sustained representation for approximately 1 second, but no longer throughout the entire delay period. We conclude by arguing for more awareness of the potentially pervasive and ubiquitous effects of eye movement-related confounds.

Significance statement

Visual working memory is an important aspect of higher cognition and has been subject of much investigation within the field of cognitive neuroscience. Over recent years, these studies have increasingly relied on the use of neural decoding techniques. Here, we show that neural decoding may be susceptible to confounds induced by stimulus-specific eye movements. Such eye movements during working memory have been reported before, and may in fact be a common phenomenon. Given the widespread use of neural decoding and the potentially contaminating effects of eye movements, we therefore believe that our results are of significant relevance for the field.
Voluntary control of illusory contour formation
Authors: Harrison William J , Rideaux Reuben
Published: November 2017

The extent to which visual inference is shaped by attentional goals is unclear. Voluntary attention may simply modulate the priority with which information is accessed by higher cognitive functions involved in perceptual decision making. Alternatively, voluntary attention may influence fundamental visual processes, such as those involved in segmenting an incoming retinal signal into a structured scene of coherent objects, thereby determining perceptual organisation. Here we tested whether the segmentation and integration of visual form can be determined by an observer’s goals by exploiting a novel variant of the classical Kanizsa figure. We generated predictions about the influence of attention with a machine classifier, and tested these predictions with a psychophysical response classification technique. Despite seeing the same image on each trial, observers’ perception of illusory spatial structure depended on their attentional goals. These attention-contingent illusory contours directly conflicted with equally plausible visual form implied by the geometry of the stimulus, revealing that attentional selection can determine the perceived layout of a fragmented scene. Attentional goals, therefore, not only select pre-computed features or regions of space for prioritised processing, but, under certain conditions, also greatly influence perceptual organisation and thus visual appearance.

SIGNIFICANCE STATEMENT

The extent to which higher cognitive functions can influence perceptual organisation is debated. The role of voluntary spatial attention, the ability to focus on only some parts of a scene, has been particularly controversial among neuroscientists and psychologists who aim to uncover the basic neural computations involved in grouping image features into coherent objects. To address this issue, we repeatedly presented the same novel ambiguous image to observers and changed their attentional goals by having them make fine spatial judgements about only some elements of the image. We found that observers’ attentional goals determine the perceived organisation of multiple illusory shapes. We thus reveal that voluntary spatial attention can control the fundamental processes that determine perceptual organisation.
Balances: a new perspective for microbiome analysis
Authors: Rivera-Pinto J. , Egozcue J.J. , Pawlowsky–Glahn V. , Paredes R. , Noguera-Julian M. , Calle M. L.
Published: November 2017

High-throughput sequencing technologies have revolutionized microbiome research by allowing the relative quantification of microbiome composition and function in different environments. One of the main goals in microbiome analysis is the identification of microbial species that are differentially abundant among groups of samples, or whose abundance is associated with a variable of interest. Most available methods for microbiome abundance testing perform univariate tests for each microbial species or taxa separately, ignoring the compositional nature of microbiome data.

We propose an alternative approach for microbiome abundance testing that consists on the identification of two groups of taxa whose relative abundance, or balance, is associated with the response variable of interest. This approach is appealing, since it has direct translation to the biological concept of ecological balance between species in an ecosystem. In this work, we present selbal, a greedy stepwise algorithm for balance selection. We illustrate the algorithm with 16s abundance data from an HIV-microbiome study and a Crohn-microbiome study.

Importance

A more meaningful approach for microbiome abundance testing is presented. Instead of testing each taxon separately we propose to explore abundance balances among groups of taxa. This approach acknowledges the compositional nature of microbiome data.
Gender-biased perceptions of important ecology articles
Authors: Bradshaw Corey J. A. , Courchamp Franck
Published: November 2017

Gender bias is still unfortunately rife in the sciences, and men co-author most articles (> 70%) in ecology. Whether ecologists subconsciously rate the quality of their peers’ work more favourably if men are the dominant co-authors is still unclear. To test this hypothesis, we examined how expert ecologists ranked important ecology articles based on a previously compiled list. Women proposed articles with a higher average proportion of women co-authors (0.18) than did men proposers (0.07). For the 100 top-ranked articles, women voters placed more emphasis on articles co-authored by women (0.06) than did men (0.02). However, women voters were still biased because they ranked men-dominated articles more highly, albeit not by as much as men did. This effect disappeared after testing read-only articles. This indicates a persistent, subconscious bias that men-dominated articles are considered to be of higher quality before actual assessment. We add that ecologists need to examine their own subconscious biases when appointing students, hiring staff, and choosing colleagues with whom to publish.
Is the HIV epidemic over? Investigating population dynamics using Bayesian methodology to estimate epidemiological parameters for a system of stochastic differential equations
Authors: Dale Renee , Guo Beibei
Published: November 2017

Current estimates of the HIV epidemic indicate a decrease in the incidence of the disease in the undiagnosed subpopulation over the past 10 years. However, a lack of access to care has not been considered when modeling the population. Populations at high risk for contracting HIV are twice as likely to lack access to reliable medical care. In this paper, we consider three contributors to the HIV population dynamics: susceptible pool exhaustion, lack of access to care, and usage of anti-retroviral therapy (ART) by diagnosed individuals. We consider the change in the proportion of undiagnosed individuals as the parameter in a simple Markov model. We obtain conservative estimates for the proportional change of the infected subpopulations using hierarchical Bayesian statistics. The estimated proportional change is used to derive epidemic parameter estimates for a system of stochastic differential equations (SDEs). Epidemic parameters are modified to capture the dynamics of each of the three contributors, as well as all their possible combinations. Model fit is quantified to determine the best explanation for the observed dynamics in the infected subpopulations.

Author summary

Using a combination of statistics and mathematical modeling, we look at some possible reasons for the reported decrease in the number of undiagnosed people living with HIV. One possibility is that the population of people at significant risk to contract HIV is being depleted (susceptibles). This might happen if significant risk for HIV infection occurs in small percentages of the overall population. Another possibility is that infected individuals lack access to care in some regions due to poverty or other cause. In this case we have to question the accuracy of the estimated size of that population. Finally, most diagnosed individuals report being on medication that reduces their viral load. This greatly reduces their chance to transmit HIV to susceptible individuals. We also combine these possibilities and look at the best explanation for the infected population size.
Effects of polyploidy on response ofDunaliella salinato salinity
Authors: Soltani Nezhad Fatemeh , Mansouri Hakimeh
Published: November 2017

In this study, effect of different percentages of polyploid cells ofDunaliella salinain culture medium, on growth and other biochemical parameters of algae under different salinity levels were investigated. The results indicated that concentration 3M NaCl is the optimal concentration of salt, since in this concentration, the highest enhancement in fresh and dry weight, chlorophyll and carotenoids, soluble sugar, glycerol, protein and starch content was observed in comparison with other concentrations. The amount of these metabolites declined in the concentrations under the optimum salinity. The least and highest amounts of MDA were observed at 1 and 4 M NaCl respectively. Polyploidy in optimum concentration of salt, caused further increment of the above growth parameters. In this relation, in most cases, treatment of 0.1% was more effective. The beneficial effects of polyploidy in non-optimal conditions were also found in some parameters such as biomass, chlorophyll, carotenoids, proteins and starch. The activity of antioxidant enzymes CAT, SOD and POD were maximum in 4 M NaCl. Polyploidy affected activity of these antioxidant enzymes in some concentrations of salt. Overall, our results suggest that the microalgae have significantly different responses to salt stress based on ploidy level of the algae.

Abbreviations

AOS

Active Oxygen Products

CAT

Catalase

GPX

Guaiacol Peroxidase

EDTA

Ethylene Diamine Tetraacetic Acid

MDA

Malondialdehyde

PMSF

Phenyl Methanesulfonyl Fluoride

PVP

Polyvinylpyrrolidone

SOD

Superoxide Dismutase
Peptide Terminus Tilting: an Unusual conformational transition of MHC Class I Revealed by Molecular Dynamics Simulations
Authors: Sun Yeping , Tian Po
Published: November 2017

A conventional picture for major histocompatibility complex class I (MHCI) antigen presentation is that the terminal anchor residues of the antigenic peptide bind to the pockets at the bottom of the MHC cleft, leaving the central peptide residues exposed for T cell antigen receptor (TCR) recognition. However, in the present study, we show that in canonical or accelerated molecular dynamics (MD) simulations, the peptide terminus in some immunodominant peptide-MHCI (pMHCI) complexes can detach from their binding pockets and stretch outside the MHC cleft. These pMHCI complexes include the complex of the H-2Kb and the lymphocytic choriomeningitis virus (LCMV) gp33 peptide, and the complex of the HLA-A*0201 and the influenza A virus M1 peptide. The detached peptide terminus becomes the most prominent spot at the pMHC interface, and so can serves as a novel TCR recognition target. Thus, peptide terminus detaching may be a novel mechanism for MHC antigen presentation.
Widespread shorter cortical adaptation in dyslexia
Authors: Jaffe-Dax Sagi , Kimel Eva , Ahissar Merav
Published: November 2017

Studies of dyslexics’ performance on perceptual tasks suggest that their implicit inference of sound statistics is impaired. In a previous paper (Jaffe-Dax, Frenkel, & Ahissar, 2017), using 2-tone frequency discrimination, we found that the effect of previous trial frequencies on dyslexics’ judgments decayed faster than the effect on controls’ judgments, and that the adaptation of their ERP responses to tones recovered faster. Here, we show the cortical distribution of this abnormal dynamics of adaptation using fast acquisition fMRI. We find that dyslexics’ faster decay of adaptation is widespread, though the most significant effects are found in the left superior temporal lobe, including the auditory cortex. This broad distribution suggests that dyslexics’ faster decay of implicit memory is a general characteristic of their cortical dynamics, which also encompasses the sensory cortices.
Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy
Authors: Bonomi M. , Pellarin R. , Vendruscolo M.
Published: November 2017

Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Since many of these systems are highly dynamical, characterising also their movements is a crucial step to unravel their biological functions. To achieve this goal, we report an integrative modelling approach to simultaneously determine structure and dynamics from cryo-electron microscopy density maps. By quantifying the level of noise in the data and dealing with their ensemble-averaged nature, this approach enables the integration of multiple sources of information to model ensembles of structures and infer their populations. We illustrate the method by characterising structure and dynamics of the integral membrane receptor STRA6, thus providing insights into the mechanisms by which it interacts with retinol binding protein and translocates retinol across the membrane.
Assessment of the aging of the brown adipose tissue by18F-FDG PET/CT imaging in the progeria mouse model LmnaG609G/G609G
Authors: Wang Zhengjie , Xu Xiaolong , Liu Yi , Gao Yongheng , Ma Ennui , Yang Welding , Kang Fei , Liu Baohua , Wang Jing
Published: November 2017

Brown adipose tissue (BAT) is an important energy metabolic organ that is closely related to obesity, type 2 diabetes, and atherosclerosis. Aging is one of the most important determinants of BAT activity. In this study, we used18F-FDG PET/CT imaging to assess the aging of the BAT in LmnaG609G/G609Gmice. To evaluate the BAT activity, LmnaG609G/G609Gand wild-type (WT) mice were injected with 18F-FDG, and PET/CT imaging was performed. The maximum standardized uptake value (SUVMax) of the BAT was measured and the target/nontarget (T/NT) values of BAT were calculated. The transcription and the protein expression levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor (β3-AR), and the PRdomain-containing16 (PRDM16), were measured by quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical analysis. Apoptosis and cell senescence of the BAT, in WT and LmnaG609G/G609Gmice, was detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14 weeks of age, the BAT SUVMaxand the expression levels of UCP1, β3-AR and PRDM16 in LmnaG609G/G609Gmice was significantly lower than that in WT mice. At the same time, the number of p16INK4a and TUNEL positively stained cells (%) increased in LmnaG609G/G609Gmice. LmnaG609G/G609Gmice are an ideal model for studying BAT aging. The aging characteristics and the aging mechanism of BAT in LmnaG609G/G609Gmice can mimic normal BAT aging.
Embryonic circular RNAs at tandem duplicated genes in zebrafish present new paradigm in gene expression
Authors: Chong-Morrison Vanessa , Sauka-Spengler Tatjana
Published: November 2017

Circular RNAs are a puzzling class of RNAs with covalently closed loop structure, lacking 5’ and 3’ ends. Present in all cells, no unifying theme has emerged regarding their function. Here, we use transcriptional data obtained by biotagging in zebrafish to uncover a high-resolution cohort of embryonic circRNAs expressed in nuclear and polysomal subcellular compartments in three developmental cell types. The ample presence of embryonic circRNAs on polysomes contradicts previous reports suggesting predominant nuclear localisation. We uncover a novel class of circRNAs, significantly enriched at tandem duplicated genes. Using newly-developed NGS-based approach, we simultaneously resolve the full sequence of putative "tandem-circRNAs" and their underlying mRNAs. These form by long-range cis-splicing events often between distant tandem duplicated genes, resulting in chimaeric mRNA transcripts and circRNAs containing their supernumerary excised exons, integrated from multiple tandem loci. Taken together, our results suggest that circularisation events rather than circRNAs themselves are functionally important.
Evaluation of nutrient stoichiometric relationships amongst ecosystem compartments of a subtropical treatment wetland. Do we have “Redfield Wetlands”?
Authors: Julian Paul , Gerber Stefan , Bhomia Rupesh K , King Jill , Osborne Todd Z. , Wright Alan L. , Powers Matthew , Dombrowski Jacob
Published: November 2017

Background

Evaluation of carbon (C), nitrogen (N) and phosphorus (P) ratios in aquatic and terrestrial ecosystems can advance our understanding of biological processes, nutrient cycling and the fate of organic matter (OM) in these ecosystems. Eutrophication of aquatic ecosystems can change the accumulation and decomposition of OM which can alter biogeochemical cycling and alter the base of the aquatic food web. This study investigated nutrient stoichiometry within and among wetland ecosystem compartments (i.e. water column, flocculent, soil and above ground vegetation biomass) of two sub-tropical treatment wetlands with distinct vegetation communities. Two flow-ways (FWs) within the network of Everglades Stormwater Treatment Areas in south Florida (USA) were selected for this study. We evaluated nutrient stoichiometry of these to understand biogeochemical cycling and controls of nutrient removal in a treatment wetland within an ecological stoichiometry context.

Results

This study demonstrates that C, N, and P stoichiometry can be highly variable among ecosystem compartments and between FWs. Power law slopes of C, N and P within surface water floc, soil and vegetation were significantly different between and along FWs.

Conclusions

Assessment of wetland nutrient stoichiometry between and within ecosystem compartments suggests unconstrained stoichiometry related to P that conforms with the notion of P limitation in the ecosystem. Differences in N:P ratios between floc and soil suggest different pathways of organic nutrient accumulation and retention between FWs. Surface nutrient stoichiometry was highly variable and decoupled (or closed to decoupled, by our criteria), in particular with respect to P. We hypothesize that decoupling may be the imprint of variability in inflow nutrient stoichiometry. However, despite active biogeochemical cycles that could act to restore nutrient stoichiometry along the FW, there was little evidence that such balancing occurred, as the degree of stochiometric decoupling in the water column did change with distance downstream. This information is only the beginning of a larger journey to understand stoichiometric processes within wetland ecosystems and how it related to ecosystem function.
Salt-bridge Dynamics in Intrinsically Disordered Proteins: A trade-off between electrostatic interactions and structural flexibility
Authors: Basu Sankar , Biswas Parbati
Published: November 2017

Intrinsically Disordered Proteins (IDPs) are enriched in charged and polar residues; and, therefore, electrostatic interactions play a predominant role in their dynamics. In order to remain multi-functional and exhibit their characteristic binding promiscuity, they need to retain considerable dynamic flexibility. At the same time, they also need to accommodate a large number of oppositely charged residues, which eventually lead to the formation of salt-bridges, imparting local rigidity. The formation of salt-bridges therefore oppose the desired dynamic flexibility. Hence, there appears to be a meticulous trade-off between the two mechanisms which the current study attempts to unravel. With this objective, we identify and analyze salt-bridges, both as isolated as well as composite ionic bond motifs, in the molecular dynamic trajectories of a set of appropriately chosen IDPs. Time evolved structural properties of these salt-bridges like persistence, associated secondary structural ′order-disorder′ transitions, correlated atomic movements, contribution in the overall electrostatic balance of the proteins have been studied in necessary detail. The results suggest that the key to maintain such a trade-off over time is the continuous formation and dissolution of salt-bridges with a wide range of persistence. Also, the continuous dynamic interchange of charged-atom-pairs (coming from a variety of oppositely charged side-chains) in the transient ionic bonds supports a model of dynamic flexibility concomitant with the well characterized stochastic conformational switching in these proteins. The results and conclusions should facilitate the future design of salt-bridges as a mean to further explore the disordered-globular interface in proteins.
Ghost interactions in MEG/EEG source space: A note of caution on inter-areal coupling measures
Authors: Palva J. Matias , Wang Sheng H. , Palva Satu , Zhigalov Alexander , Monto Simo , Brookes Matthew J. , Schoffelen Jan-Mathijs , Jerbi Karim
Published: November 2017

When combined with source modeling, magneto‐ (MEG) and electroencephalography (EEG) can be used to study long-range interactions among cortical processes non-invasively. Estimation of such inter-areal connectivity is nevertheless hindered by instantaneous field spread and volume conduction, which artificially introduce linear correlations and impair source separability in cortical current estimates. To overcome the inflating effects of linear source mixing inherent to standard interaction measures, alternative phase‐ and amplitude-correlation based connectivity measures, such as imaginary coherence and orthogonalized amplitude correlation have been proposed. Being by definition insensitive to zero-lag correlations, these techniques have become increasingly popular in the identification of correlations that cannot be attributed to field spread or volume conduction. We show here, however, that while these measures are immune to the direct effects of linear mixing, they may still reveal large numbers of spurious false positive connections through field spread in the vicinity of true interactions. This fundamental problem affects both region-of-interest-based analyses and all-to-all connectome mappings. Most importantly, beyond defining and illustrating the problem of spurious, or “ghost” interactions, we provide a rigorous quantification of this effect through extensive simulations. Additionally, we further show that signal mixing also significantly limits the separability of neuronal phase and amplitude correlations. We conclude that spurious correlations must be carefully considered in connectivity analyses in MEG/EEG source space even when using measures that are immune to zero-lag correlations.

Highlights

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Reliable estimation of neuronal coupling with MEG and EEG is challenged by signal mixing

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A number of coupling techniques attempt to overcome this limitation by excluding zero-lag interactions

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Contrary to what is commonly admitted, our simulations illustrate that such interaction metrics will still yield false positives

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Spurious, or “ghost”, interactions are generally detected between sources in the vicinity of true phase-lagged interacting sources

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Signal mixing also severely affects the mutual separability of phase and amplitude correlations
Dissecting single–cell molecular spatiotemporal mobility and clustering at Focal Adhesions in polarised cells by fluorescence fluctuation spectroscopy methods
Authors: Garcia Esther , Bernardino de la Serna Jorge
Published: November 2017

Quantitative fluorescence fluctuation spectroscopy from optical microscopy datasets is a very powerful tool to resolve multiple spatiotemporal cellular and subcellular processes at the molecular level. In particular, raster image correlation spectroscopy (RICS) and number and brightness analyses (N&B) yield molecular mobility and clustering dynamic information extracted from real-time cellular processes. This quantitative information can be inferred in a highly flexibly and detailed manner, i.e. 1) at the localisation level: from full-frame datasets and multiple regions of interest within; and 2) at the temporal level: not only from full-frame and multiple regions, but also intermediate temporal events. Here we build on previous research in deciphering the molecular dynamics of paxillin, a main component of focal adhesions. Cells use focal adhesions to attach to the extracellular matrix and interact with their local environment. Through focal adhesions and other adhesion structures, cells sense their local environment and respond accordingly; due to this continuous communication, these structures can be highly dynamic depending on the extracellular characteristics. By using a previously well-characterised model like paxillin, we examine powerful sensitivity characteristics and some limitations of RICS and N&B analyses. We show that cells upon contact to different surfaces show differential self-assembly dynamics in terms of molecular diffusion and oligomerisation. In addition, single-cell studies show that these dynamics change gradually following an antero-posterior gradient.
Noise-driven cell differentiation and the emergence of spatiotemporal patterns
Authors: Safdari Hadiseh , Kalirad Ata , Picioreanu Cristian , Tusserkani Rouzbeh , Goliaei Bahram , Sadeghi Mehdi
Published: November 2017

One of the major transitions in evolution is the step from unicellularity into the brave new world of multicellularity. To understand this feat, one has to fathom two main characteristics of multicellular organisms: differentiation and self-organization. Any explanation concerning this major transition should involve mechanisms that can simultaneously explain the marvellous intricacies manifest in the aforementioned characteristics, and an account of the evolution of such traits. Here we propose a noise-driven differentiation (NDD) model. The reliance on noise, in place of a more mechanistic approach, makes the NDD model a more suitable approach to explain differentiation and self-organization. Furthermore, our model sheds some light on the possible evolutionary origins of these biological innovations. To test the NDD model, we utilize a model of cell aggregation. The behavior of this model of cell aggregation is in concert with the NDD model.
Organization of Neural Population Code in Mouse Visual System
Authors: Esfahany Kathleen , Siergiej Isabel , Zhao Yuan , Park Il Memming
Published: November 2017

The mammalian visual system consists of several anatomically distinct areas, layers, and cell types. To understand the role of these subpopulations in visual information processing, we analyzed neural signals recorded from excitatory neurons from various anatomical and functional structures. For each of 186 mice, one of six genetically tagged cell-types and one of six visual areas were targeted while the mouse was passively viewing various visual stimuli. We trained linear classifiers to decode one of six visual stimulus categories with distinct spatiotemporal structures from the population neural activity. We found that neurons in both the primary visual cortex and secondary visual areas show varying degrees of stimulus-specific decodability, and neurons in superficial layers tend to be more informative about the stimulus categories. Additional decoding analyses of directional motion were consistent with these findings. We observed synergy in the population code of direction in several visual areas suggesting area-specific organization of information representation across neurons. These differences in decoding capacities shed light on the specialized organization of neural information processing across anatomically distinct subpopulations, and further establish the mouse as a model for understanding visual perception.
A FRET based biosensor for measuring Gα13 activation in single cells
Authors: Mastop Marieke , Reinhard Nathalie R. , Zuconelli Cristiane R. , Terwey Fenna , Gadella Theodorus W. J. , van Unen Jakobus , Adjobo-Hermans Merel J. W. , Goedhart Joachim
Published: November 2017

Förster Resonance Energy Transfer (FRET) provides a way to directly observe the activation of heterotrimeric G-proteins by G-protein coupled receptors (GPCRs). To this end, FRET based biosensors are made, employing heterotrimeric G-protein subunits tagged with fluorescent proteins. These FRET based biosensors complement existing, indirect, ways to observe GPCR activation. Here we report on the insertion of mTurquoise2 at several sites in the human Gα13 subunit. Three variants were found to be functional based on i) plasma membrane localization and ii) ability to recruit p115-RhoGEF upon activation of the LPA2 receptor. The tagged Gα13 subunits were used as FRET donor and combined with cp173Venus fused to the Gγ2 subunit as the acceptor. We constructed Gα13 biosensors by generating a single plasmid that produces Gα13-mTurquoise2, Gβ1 and cp173Venus-Gγ2. The Gα13 activation biosensors showed a rapid and robust response when used in primary human endothelial cells that were treated with thrombin, triggering endogenous protease activated receptors (PARs). This response was efficiently inhibited by the RGS domain of p115-RhoGEF and from the biosensor data we inferred that this is due to GAP activity. Finally, we demonstrated that the Gα13 sensor could be used to dissect heterotrimeric G-protein coupling efficiency in single living cells. We conclude that the Gα13 biosensor is a valuable tool for live-cell measurements that probe Gα13 activation.
TGF-β1 enhances mouse mast cell release of IL-6 and IL-13
Authors: Lyons David O. , Plewes Michele R. , Pullen Nicholas A.
Published: November 2017

For immune cells, TGF-β1 can enhance or repress effector functions. Here, we characterize the effects of TGF-β1 on IgE-mediated activation of primary murine mast cells derived from hematopoietic stem cells (BMMC). We also investigated potential interaction between TGF-β1 and stem-cell factor (SCF). Resting IL-6 production was increased with TGF-β1 but significance was lost following BMMC activation via IgE receptor (FcεRI) crosslinking. SCF also enhanced resting levels of IL-6, but there was no difference from control once FcεRI was engaged. SCF had no effect on IL-13 production; however, TGF-β1 treatment enhanced release of IL-13 upon FcεRI activation. Lastly, percent colocalization of SCF receptor (CD117) and FcεRI were unaffected by TGF-β1 treatment. These data reveal a novel positive effect of soluble TGF-β1 on mast cell activation.
The fractured landscape of RNA-seq alignment: The default in our STARs
Authors: Ballouz Sara , Dobin Alexander , Gingeras Thomas , Gillis Jesse
Published: November 2017

Many tools are available for RNA-seq alignment and expression quantification, with comparative value being hard to establish. Benchmarking assessments often highlight methods’ good performance, but are focused on either model data or fail to explain variation in performance. This leaves us to ask, what is the most meaningful way to assess different alignment choices? And importantly, where is there room for progress? In this work, we explore the answers to these two questions by performing an exhaustive assessment of the STAR aligner. We assess STAR’s performance across a range of alignment parameters using common metrics, and then on biologically focused tasks. We find technical metrics such as fraction mapping or expression profile correlation to be uninformative, capturing properties unlikely to have any role in biological discovery. Surprisingly, we find that changes in alignment parameters within a wide range have little impact on both technical and biological performance. Yet, when performance finally does break, it happens in difficult regions, such as X-Y paralogs and MHC genes. We believe improved reporting by developers will help establish where results are likely to be robust or fragile, providing a better baseline to establish where methodological progress can still occur.
Sensory attenuation is related to dopamine dose in Parkinson’s disease
Authors: Wolpe Noham , Zhang Jiaxiang , Nombela Cristina , Ingram James N , Wolpert Daniel M ,   Cam-CAN, Rowe James B.
Published: November 2017

Abnormal initiation and control of voluntary movements are among the principal manifestations of Parkinson’s disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, and increases the relative salience of unexpected stimuli to facilitate the control of movements. We examined this integration process and its relation to dopamine in PD, by measuring sensorimotor attenuation – the reduction in the perceived intensity of predicted sensations from self-generated versus external actions. Patients with idiopathic PD (n=18) and population-derived controls (n=175) matched a set of target forces applied to their left index finger by a torque motor. To match the force, participants either pressed with their right index finger (‘Direct’ condition) or used a linear potentiometer that controlled a motor (‘Slider’ condition). We found that despite changes in sensitivity to different forces, overall sensory attenuation did not differ between medicated PD patients and controls. Importantly, the degree of attenuation was negatively related to PD motor severity but positively related to individual patient dopamine dose, as measured by levodopa dose equivalency. The results suggest that dopamine could regulate the integration of sensorimotor prediction with sensory information to facilitate the control of voluntary movements.
Performance-optimized hierarchical models only partially predict neural responses during perceptual decision making
Authors: Gwilliams Laura , King Jean-Rémi
Published: November 2017

Models of perceptual decision making have historically been designed to maximally explain behaviour and brain activity independently of their ability to actually perform tasks. More recently, performance-optimized models have been shown to correlate with brain responses to images and thus present a complementary approach to understand perceptual processes. In the present study, we compare how these approaches comparatively account for the spatio-temporal organization of neural responses elicited by ambiguous visual stimuli. Forty-six healthy human subjects performed perceptual decisions on briefly flashed stimuli constructed from ambiguous characters. The stimuli were designed to have 7 orthogonal properties, ranging from low-sensory levels (e.g. spatial location of the stimulus) to conceptual (whether stimulus is a letter or a digit) and task levels (i.e. required hand movement). Magneto-encephalography source and decoding analyses revealed that these 7 levels of representations are sequentially encoded by the cortical hierarchy, and actively maintained until the subject responds. This hierarchy appeared poorly correlated to normative, drift-diffusion, and 5-layer convolutional neural networks (CNN) optimized to accurately categorize alpha-numeric characters, but partially matched the sequence of activations of 3/6 state-of-the-art CNNs trained for natural image labeling (VGG-16, VGG-19, MobileNet). Additionally, we identify several systematic discrepancies between these CNNs and brain activity, revealing the importance of single-trial learning and recurrent processing. Overall, our results strengthen the notion that performance-optimized algorithms can converge towards the computational solution implemented by the human visual system, and open possible avenues to improve artificial perceptual decision making.
Hard Limits and Performance Tradeoffs in a Class of Sequestration Feedback Systems
Authors: Olsman Noah , Baetica Ania-Ariadna , Xiao Fangzhou , Leong Yoke Peng , Murray Richard M. , Doyle John C.
Published: November 2017

Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism implemented using the sequestration binding of two molecules. Our work develops an analytic framework for understanding the hard limits, performance tradeoffs, and architectural properties of this simple model of biological feedback control. Using tools from control theory, we show that there are simple parametric relationships that determine both the stability and the performance of these systems in terms of speed, robustness, steady-state error, and leakiness. These findings yield a holistic understanding of the behavior of sequestration feedback and contribute to a more general theory of biological control systems.