bluuebunny/crossref_metadata_2025 huggingface dataset:
Cavernous Sinus and Parasellar Region: An Endoscopic Endonasal Anatomic Cadaver Dissection
Authors: Erdogan Umut , Turhal Goksel , Kaya Isa , Biceroglu Huseyin , Midilli Rasit , Gode Sercan , Karci Bulent
Published: October 2018

The aim of this study was to investigate the neurovascular structures of the cavernous sinus with the endonasal endoscopic transpterygoid approach on fresh human cadavers. Additionally, the course of internal carotid artery (ICA) and relevant anatomy was thoroughly investigated to refine the anatomical landmarks, exposure difficulties, potential complications, and limitations using the endonasal endoscopic technique. This study was carried out at an otolaryngology department of a tertiary medical center between June 2014 and June 2015. The surgical dissection was performed on 10 fresh human cadaver specimens using paranasal sinus and skull base endoscopic instruments. Cavernous sinuses and parasellar area were explored via an endoscopic endonasal transpterygoid approach. Dehiscence was present in 5 (25%) cavernous ICAs. Projection of the cavernous ICA on the whole lateral sphenoid wall was prominent in 6 (%30) sphenoid sinuses. Anterior curve was prominent in 12 (60%) cavernous ICAs, whereas posterior was prominent in 7 (35%). Mean distance between the lateral wall of eustachian tube orifice and petrous ICA was 19.50 ± 1.05 mm (range 18–22 mm). Cranial nerves of the cavernous sinus showed no variation. Control of the ICA is critical during the endonasal endoscopic approach to the cavernous sinus and skull base. The vidian nerve is a reliable and important landmark to the petrous ICA in the transpterygoid approach. Dissection of the eustachian tube and its relation to the ICA has to be kept in mind during nasopharyngeal surgery.
The Role of Mitochondrial DNA in the Development of Ischemia Reperfusion Injury
Authors: Hu Qiongyuan , Zhou Quan , Wu Jie , Wu Xiuwen , Ren Jianan
Published: October 2018

Ischemia/reperfusion (I/R) injury is a common occurrence resulting from acute mesenteric ischemia, traumatic or septic shock, burns, and surgical procedures that can lead to multiple organ failure and high mortality in critically ill patients. Mitochondria are often considered the cellular power factory via their capacity for ATP generation. Recently, mitochondria have been further identified as vital regulators of cell death, inflammation, and oxidative stress, all of which can aggravate I/R injury. Studies have indicated that mitochondrial DNA (mtDNA) damage leads to mitochondrial dysfunction and aggravates I/R injury. mtDNA is emerging as an agonist of the innate immune system that influences inflammatory pathology during I/R injury. In addition, when mtDNA is released into the cytoplasm, extracellular milieu, or circulation, it can activate multiple pattern-recognition receptors to trigger type I interferon and pro-inflammatory responses. Here, we review the emerging role of mtDNA in I/R injury to highlight novel mechanistic insights and discuss the pathophysiological relevance of mitochondrial biology.
Stimulation of N-methyl-D-aspartate receptors by exogenous and endogenous ligands improves outcome of brain injury
Authors: Biegon Anat , Liraz-Zaltsman Sigal , Shohami Esther
Published: October 2018

Purpose of review

The failure of N-methyl-D-aspartate receptor (NMDAR) antagonists as a treatment for human traumatic brain injury (TBI) and stroke, along with preclinical findings of a persistent hypofunctional state of these receptors after brain injury, resulted in a new focus on NMDAR agonists, specifically those acting via the glycine site of the NMDAR. This article reviews the recent literature on positive modulators of the glycine site as a new modality for improving cognitive function in central nervous system pathology, including traumatic and ischemic brain injuries, neuroinflammation, and neuropsychiatric disorders.

Recent findings

A sustained cognitive decline and NMDAR downregulation were reported in rodent models of TBI, developmental TBI, stroke, and lipopolysaccharide-induced neuroinflammation. Activation of the glycine/serine site by D-cycloserine (DCS) or D-serine ameliorated these cognitive deficits. Recent reviews and reports on the use of DCS and D-serine to modify memory function in a wide range of psychiatric conditions are generally positive.

Taken together, the preclinical and clinical studies provide new, additional support for the notion that activation of the glycine/serine site should be considered a novel therapeutic approach to cognitive impairments. Specifically, as DCS is an approved drug, its translation into clinical practice should be advocated.
Role of amino-tracer PET for decision-making in neuro-oncology
Authors: Suchorska Bogdana , Albert Nathalie L. , Tonn Jörg-Christian
Published: October 2018

Purpose of review

To give an overview on the current development in PET imaging as an additional tool in brain tumor management.

Recent findings

The rising emphasis on molecular tumor characteristics both in primary and in metastatic brain disease leads to an increased demand for noninvasive ‘molecular’ grading as well as treatment planning and surveillance of therapy effects. Metabolic imaging using amino acid PET provides further insights into tumor metabolism; current novelties comprise the use of hybrid PET/MRI scanners as well as development of new tracers. Furthermore, treatment monitoring and prognostication on the basis of amino acid PET is gaining further importance in neuro-oncological decision-making.

Due to its unique properties in visualization of tumor biology, amino acid PET will continue to gain further importance in primary and secondary brain tumors.
Current and future tools for determination and monitoring of isocitrate dehydrogenase status in gliomas
Authors: Picca Alberto , Di Stefano Anna L. , Sanson Marc
Published: October 2018

Purpose of review

Hotspot mutations of isocitrate dehydrogenase 1 (R132) or 2 (R172) genes affect 40% of diffuse gliomas, mostly grades II and III. The mutant enzyme produces high quantities of d-2-hydroxyglutarate (D2HG), which reshapes the epigenetic of the cell leading to gliomagenesis. For the clinician, the isocitrate dehydrogenase (IDH) mutation is a major biomarker with diagnostic, prognostic, and predictive consequences. With the development of specific inhibitors and vaccination, it appears also a potential actionable target.

Recent findings

IDH status is routinely determined on tumor sample by sequencing and immunohistochemistry detecting the most common mutant protein (IDH1R132H). Recently noninvasive diagnostic approaches have been developed based on the detection of the mutant DNA or the D2HG in body fluids, and the detection of D2HG by magnetic resonance spectroscopy of the brain.

These new techniques open avenues for non invasive diagnostic of glioma in patients not amenable to biopsy, in the preoperative setting and also duringpatients follow-up for evaluation of treatment response and prediction of recurrence.
Movement Disorders After Exposure to Antipsychotic Drugs in Patients With Depressive Disorders
Authors: Rey María Verónica , Molina Luis , Recinos Byron , Paz Bezner , Rovelo Mauricio , Rodriguez Elias Fanny Elizabeth , Calderón José , Arellano Arturo , Perez-Lloret Santiago
Published: October 2018

Objectives

The aims of the study were to explore the frequency of movement disorders (MDs) in depressive patients exposed to antipsychotic drugs (APDs) and to compare it with nonexposed depressive patients and APDs-treated schizophrenic patients.

Methods

Four hundred fifty-two depressive patients not exposed to APDs (group A), 156 depressives exposed to APDs (group B), and 75 patients with schizophrenia on APDs (group C) were recruited. Presence of MDs was explored by the Simpson-Angus and UKU scales (Registration: NCT02409823).

Results

Movement disorders were observed in 5%, 9%, and 13% of patients in groups A to C, respectively (P < 0.001, χ2 for linear trend). A logistic multivariate analysis revealed that male sex (odds ratio = 2.26, 95% confidence interval = 1.13–4.49, P < 0.01), exposure to first-generation (vs second-generation) APDs (odds ratio = 5.71, 95% confidence interval = 2.08–15.66, P < 0.01), and exposure to lithium (odds ratio = 3.99, 95% confidence interval = 1.74–9.14, P < 0.01) were independently and significantly associated with MDs.

Conclusions

Male sex, use first-generation APDs, and exposure to lithium were associated with MDs in depression. Therefore, caution is advised with the use of these drugs in depressive patients. Prospective studies are needed to confirm these results.
The social situation affects how we process feedback about our actions
Authors: Czeszumski Artur , Ehinger Benedikt V. , Wahn Basil , König Peter
Published: October 2018

Humans achieve their goals in joint action tasks either by cooperation or competition. In the present study, we investigated the neural processes underpinning error and monetary rewards processing in such cooperative and competitive situations. We used electroencephalography (EEG) and analyzed event-related potentials (ERPs) triggered by feedback in both social situations. 26 dyads performed a joint four-alternative forced choice (4AFC) visual task either cooperatively or competitively. At the end of each trial, participants received performance feedback about their individual and joint errors and accompanying monetary rewards. Furthermore, the outcome, i.e. resulting positive, negative or neutral rewards, was dependent on the pay-off matrix, defining the social situation either as cooperative or competitive. We used linear mixed effects models to analyze the feedback-related-negativity (FRN) and used the Thresholdfree cluster enhancement (TFCE) method to explore activations of all electrodes and times. We found main effects of the outcome and social situation at mid-line frontal electrodes. The FRN was more negative for losses than wins in both social situations. However, the FRN amplitudes differed between social situations. Moreover, we compared monetary with neutral outcomes in both social situations. Our exploratory TFCE analysis revealed that processing of feedback differs between cooperative and competitive situations at right temporo-parietal electrodes where the cooperative situation elicited more positive amplitudes. Further, the differences induced by the social situations were stronger in participants with higher scores on a perspective taking test. In sum, our results replicate previous studies about the FRN and extend them by comparing neurophysiological responses to positive and negative outcomes in a task that simultaneously engages two participants in competitive and cooperative situations.
Efficient feature selection on gene expression data: Which algorithm to use?
Authors: Tsagris Michail , Papadovasilakis Zacharias , Lakiotaki Kleanthi , Tsamardinos Ioannis
Published: October 2018

Background

Feature selection seeks to identify a minimal-size subset of features that is maximally predictive of the outcome of interest. It is particularly important for biomarker discovery from high-dimensional molecular data, where the features could correspond to gene expressions, Single Nucleotide Polymorphisms (SNPs), proteins concentrations, e.t.c. We evaluate, empirically, three state-of-the-art, feature selection algorithms, scalable to high-dimensional data: a novel generalized variant of OMP (gOMP), LASSO and FBED. All three greedily select the next feature to include; the first two employ the residuals re-sulting from the current selection, while the latter rebuilds a statistical model. The algorithms are compared in terms of predictive performance, number of selected features and computational efficiency, on gene expression data with either survival time (censored time-to-event) or disease status (case-control) as an outcome. This work attempts to answer a) whether gOMP is to be preferred over LASSO and b) whether residual-based algorithms, e.g. gOMP, are to be preferred over algorithms, such as FBED, that rely heavily on regression model fitting.

Results

gOMP is on par, or outperforms LASSO in all metrics, predictive performance, number of features selected and computational efficiency. Contrasting gOMP to FBED, both exhibit similar performance in terms of predictive performance and number of selected features. Overall, gOMP combines the benefits of both LASSO and FBED; it is computationally efficient and produces parsimonious models of high predictive performance.

Conclusions

The use of gOMP is suggested for variable selection with high-dimensional gene expression data, and the target variable need not be restricted to time-to-event or case control, as examined in this paper.
Genetic variants influence on the placenta regulatory landscape
Authors: Delahaye F. , Do C. , Kong Y. , Ashkar R. , Sala M. , Tycko B. , Wapner R. , Hughes F.
Published: October 2018

Background

From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications.

Results

By producing and analyzing DNA sequence variation (n=303), DNA methylation (n=303) and mRNA expression data (n=80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations.

Conclusions

These findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.

Author summary

The placenta is a critical organ playing multiple roles including oxygen and metabolite transfer from mother to fetus, hormone production, and vascular perfusion. With this study, we aimed to deliver a placenta-specific regulatory map based on a combination of publicly available and newly generated data. To complete this reference, we obtained genotype information (n=303), DNA methylation (n=303) and expression data (n=80) for placentas from healthy women. Our analysis of methylation and expression quantitative trait loci (QTLs) and correlations between methylation and expression data were designed to identify fundamental associations between genome, transcriptome, and epigenome in this key fetal organ. The results provide high-resolution genetic and epigenetic maps specific to the placenta based on a representative ethnically diverse cohort. As interest and efforts are growing to better understand the etiology of placental disease and the impact of the environment on placental function these data will provide a reference and enhance future investigations.
Novel Data Transformations for RNA-seq Data Analysis
Authors: Zhang Zeyu , Yu Danyang , Seo Minseok , Hersh Craig P. , Weiss Scott T. , Qiu Weiliang
Published: October 2018

We propose eight data transformations for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that limma based on transformed data by using the rv transformation (denoted as limma+rv) performed best compared with limma based on transformed data by using other transformation methods in term of high accuracy and low FNR, while keeping FDR at the nominal level. For large sample size, limma based on transformed data by using the 8 proposed transformation methods had similar performance to limma based on transformed data by using existing transformation methods for equal library size scenarios. Otherwise, limma based on transformed data by using the rv, lv, rv2, or lv2 transformation, or by using the existing voom transformation performed better than limma based on data from other transformation methods. Real data analysis results showed that limma+ l2 performed best, while limma+ rv also had good performance.
The geography of the Anthropocene differs between the land and the sea
Authors: Bowler D.E. , Bjorkman A.D. , Dornelas M. , Myers-Smith I.H. , Navarro L. M. , Niamir A. , Supp S.R. , Waldock C. , Vellend M. , Blowes S. A. , Böhning-Gaese K. , Bruelheide H. , Elahi R. , Antão L.H. , Hines J. , Isbell F. , Jones H.P. , Magurran A.E. , Cabral J. S. , Winter M. , Bates A.E.
Published: October 2018

Climate change and other anthropogenic drivers of biodiversity change are unequally distributed across the world. The geographic patterns of different drivers, and the spatial overlap among these drivers, have important implications for the direction and pace of biodiversity change, yet are not well documented. Moreover, it is unknown if the geographic patterns of drivers differ between the terrestrial and marine realm, as expected due to marked differences in how humans interact with the land and ocean.

We compiled global gridded datasets on climate change, land-use, resource exploitation, pollution, species invasions, and human population density. We used multivariate statistics to examine the spatial relationships among the datasets and to characterize the typical combinations of drivers experienced by different parts of the world.

We found stronger positive correlations among drivers in the terrestrial than in the marine realm, leading to areas of high intensities of multiple drivers on land. Climate change tended to be negatively correlated with other drivers in the terrestrial realm (e.g., in the tundra and boreal forest with high climate change but low human use and pollution) whereas the opposite was true in the marine realm (e.g., in the Indo-Pacific with high climate change and high fishing).

We show that different regions of the world can be defined by anthropogenic threat complexes (ATCs), distinguished by different sets of drivers with varying intensities. The ATCs can be used to test hypothesis about the pattern of biodiversity change, especially the joint effects of multiple drivers. More generally, our global analysis highlights the broad conservation priorities needed to mitigate the effects of anthropogenic change on biodiversity responses, with different priorities emerging on land and in the ocean, and in different parts of the world.
Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2′-C-methyladenosine prevents death in a mouse model of West Nile virus infection
Authors: Eyer Luděk , Fojtíková Martina , Nencka Radim , Rudolf Ivo , Hubálek Zdeněk , Ruzek Daniel
Published: October 2018

West Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2′-C- methyl- or 4′-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative ofC2′-methylated nucleosides, 7-deaza-2′-C- methyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days post-infection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2′-C- methyladenosine was absent or negligible when the treatment was started 8 days post-infection (i.e., at the time of extensive brain infection). The 4′-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replication in vitro. However, the strong anti-WNV effect of 4′-azidocytidine and 4′-azido-aracytidine was cell type-dependent and observed predominantly in PS cells. The effect was much less pronounced in Vero cells. Our results indicate that 2′-C- methylated or 4′-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections, as well as infections caused by other medically important flaviviruses.
Identification of C. elegans strains using a fully convolutional neural network on behavioural dynamics
Authors: Javer Avelino , Brown André E.X. , Kokkinos Iasonas , Rittscher Jens
Published: October 2018

The nematode C. elegans is a promising model organism to understand the genetic basis of behaviour due to its anatomical simplicity. In this work, we present a deep learning model capable of discerning genetically diverse strains based only on their recorded spontaneous activity, and explore how its performance changes as different embeddings are used as input. The model outperforms hand-crafted features on strain classification when trained directly on time series of worm postures.
PCAGO: An interactive web service to analyze RNA-Seq data with principal component analysis
Authors: Gerst Ruman , Hölzer Martin
Published: October 2018

The initial characterization and clustering of biological samples is a critical step in the analysis of any transcriptomic study. In many studies, principal component analysis (PCA) is the clustering algorithm of choice to predict the relationship of samples or cells based solely on differential gene expression. In addition to the pure quality evaluation of the data, a PCA can also provide initial insights into the biological background of an experiment and help researchers to interpret the data and design the subsequent computational steps accordingly. However, to avoid misleading clusterings and interpretations, an appropriate selection of the underlying gene sets to build the PCA and the choice of the most fitting principal components for the visualization are crucial parts. Here, we present PCAGO, an easy-to-use and interactive web service to analyze gene quantification data derived from RNA sequencing (RNA-Seq) experiments with PCA. The tool includes features such as read-count normalization, filtering of read counts by gene annotation, and various visualization options. Additionally, PCAGO helps to select appropriate parameters such as the number of genes and principal components to create meaningful visualizations.

Availability and implementation

The web service is implemented in R and freely available at pcago.bioinf.uni-jena.de.

Contact

martin.hoelzer@uni-jena.de
When sinks become sources: adaptive colonization in asexuals
Authors: Lavigne Florian , Martin Guillaume , Anciaux Yoann , Papaϯx Julien , Roques Lionel
Published: October 2018

The successful establishment of a population into a new empty habitat outside of its initial niche is a phenomenon akin to evolutionary rescue in the presence of immigration. It underlies a wide range of processes, such as biological invasions by alien organisms, host shifts in pathogens or the emergence of resistance to pesticides or antibiotics from untreated areas.

In this study, we derive an analytically tractable framework to describe the coupled evolutionary and demographic dynamics of asexual populations in a source-sink system. In particular, we analyze the influence of several factors — immigration rate, mutational parameters, and harshness of the stress induced by the change of environment — on the establishment success in the sink (i.e. the formation of a self-sufficient population in the sink), and on the time until establishment. To this aim, we use a classic phenotype-fitness landscape (Fisher’s geometrical model inndimensions) where source and sink habitats determine distinct phenotypic optima. The harshness of stress, in the sink, is determined by the distance between the fitness optimum in the sink and that of the source. The dynamics of the full distribution of fitness and of population size in the sink are analytically predicted under a strong mutation strong immigration limit where the population is always polymorphic.

The resulting eco-evolutionary dynamics depend on mutation and immigration rates in a non straightforward way. Below some mutation rate threshold, establishment always occurs in the sink, following a typical four-phases trajectory of the mean fitness. The waiting time to this establishment is independent of the immigration rate and decreases with the mutation rate. Beyond the mutation rate threshold, lethal mutagenesis impedes establishment and the sink population remains so, albeit with an equilibrium state that depends on the details of the fitness landscape. We use these results to get some insight into possible effects of several management strategies.
Diverse food-sensing neurons trigger idiothetic local search in Drosophila
Authors: Corfas Román A. , Dickinson Michael H.
Published: October 2018

Resources are often sparsely clustered in nature. Thus, foraging animals may benefit from remembering the location of a newly discovered food patch while continuing to explore nearby [1, 2]. For example, after encountering a drop of yeast or sugar, hungry flies often perform a local search consisting of frequent departures and returns to the food site [3, 4]. Fruit flies, Drosophila melanogaster, can perform this food-centered search behavior in the absence of external stimuli or landmarks, instead relying solely on internal (idiothetic) cues to keep track of their location [5]. This path integration behavior may represent a deeply conserved navigational capacity in insects [6, 7], but the neural pathways underlying food-triggered searches remain unknown. Here, we used optogenetic activation to screen candidate cell classes and found that local searches can be initiated by diverse sensory neurons including sugar-sensors, water-sensors, olfactory-receptor neurons, as well as hunger-signaling neurons of the central nervous system. Optogenetically-induced searches resemble those triggered by actual food and are modulated by starvation state. Furthermore, search trajectories exhibit key features of path integration: searches remain tightly centered around the fictive-food site, even during long periods without reinforcement, and flies re-center their searches when they encounter a new fictive-food site. Flies can even perform elaborate local searches within a constrained maze. Together, these results suggest that flies enact local searches in response to a wide variety of food-associated cues, and that these sensory pathways may converge upon a common neural system for path integration. Optogenetically induced local searches in Drosophila can now serve as a tractable system for the study of spatial memory and navigation in insects.
A Bayesian psychophysics model of sense of agency
Authors: Legaspi Roberto , Toyoizumi Taro
Published: October 2018

Despite the increasing significance of sense of agency (SoA) research, the literature lacks a formal model: what computational principles underlie SoA, the registration that oneself initiated an action that caused something to happen? We theorize SoA in the framework of optimal Bayesian cue integration with mutually involved principles, namely, reliability of action and outcome sensory signals, their consistency with the causation of the outcome by the action, and the prior belief in causation. We used our Bayesian model to explain the intentional binding effect, hailed as reliable indicator of SoA. Our model explains temporal binding in both self-intended and unintentional actions suggesting that intentionality is not strictly necessary given high confidence in the action causing the outcome. Our Bayesian model also explains that if the sensory cues are reliable, SoA can emerge even for unintended actions. Our formal model therefore posits a precision-dependent causal agency.
The Effects of Global Signal Regression on Estimates of Resting-state BOLD fMRI and EEG Vigilance Correlations
Authors: Falahpour Maryam , Nalci Alican , Liu Thomas T.
Published: October 2018

Global signal regression (GSR) is a commonly used albeit controversial preprocessing approach in the analysis of resting-state BOLD fMRI data. While the effects of GSR on resting-state functional connectivity measures have received much attention, there has been relatively little attention devoted to its effects on studies looking at the relation between resting-state BOLD measures and independent measures of brain activity. In this study we used simultaneously acquired EEG-fMRI data in humans to examine the effects of GSR on the correlation between resting-state BOLD fluctuations and EEG vigilance measures. We show that GSR leads to a positive shift in the correlation between the BOLD and vigilance measures. This shift leads to a reduction in the spatial extent of negative correlations in widespread brain areas, including the visual cortex, but leads to the appearance of positive correlations in other areas, such as the cingulate gyrus. The results obtained using GSR are consistent with those of a temporal censoring process in which the correlation is computed using a temporal subset of the data. Since the data from these retained time points are unaffected by the censoring process, this finding suggests that the positive correlations in cingulate gyrus are not simply an artifact of GSR.
Histone deacetylase inhibitor treatment promotes spontaneous caregiving behavior in C57BL/6J male mice
Authors: Mayer H.S. , Crepeau M. , Duque-Wilckens N. , Torres L.Y. , Trainor B.C. , Stolzenberg D.S.
Published: October 2018

Whereas the majority of mammalian species are uni-parental with the mother solely provisioning care for young conspecifics, fathering behaviors can emerge under certain circumstances. For example, a great deal of individual variation in response to young pups has been reported in multiple inbred strains of laboratory male mice. Further, sexual experience and subsequent cohabitation with a female conspecific can induce caregiving responses in otherwise indifferent, fearful or aggressive males. Thus, a highly conserved parental neural circuit is likely present in both sexes, however the extent to which infants are capable of accessing this circuit may vary. In support of this idea, fearful or indifferent responses toward pups in female mice are linked to greater immediate early gene (IEG) expression in a fear/defensive circuit involving the anterior hypothalamus than in an approach/attraction circuit involving the ventral tegmental area. However, experience with infants, particularly in combination with histone deacetylase inhibitor (HDACi) treatment, can reverse this pattern of neuronal activation and behavior. Thus, HDACi treatment may increase the transcription of primed/poised genes that play a role in the activation and selection of a maternal approach circuit in response to pup stimuli. Here, we asked whether HDACi treatment would impact behavioral response selection and associated IEG expression changes in virgin male mice that are capable of ignoring, attacking or caring for pups. Our results indicate that systemic HDACi treatment induces spontaneous caregiving behavior in non-aggressive male mice and alters the pattern of pup-induced IEG expression across a fear/defensive neural circuit.
One Health genomic surveillance ofEscherichia colidemonstrates distinct lineages and mobile genetic elements in isolates from humans versus livestock
Authors: Ludden Catherine , Raven Kathy E. , Jamrozy Dorota , Gouliouris Theodore , Blane Beth , Coll Francesc , de Goffau Marcus , Naydenova Plamena , Horner Carolyne , Hernandez-Garcia Juan , Wood Paul , Hadjirin Nazreen , Radakovic Milorad , Brown Nicholas M. , Holmes Mark , Parkhill Julian , Peacock Sharon J.
Published: October 2018

Livestock have been proposed as a reservoir for drug-resistantEscherichia colithat infect humans. We isolated and sequenced 431E. coli(including 155 ESBL-producing isolates) from cross-sectional surveys of livestock farms and retail meat in the East of England. These were compared with the genomes of 1517E. coliassociated with bloodstream infection in the United Kingdom. Phylogenetic core genome comparisons demonstrated that livestock and patient isolates were genetically distinct, indicating thatE. colicausing serious human infection do not directly originate from livestock. By contrast, we observed highly related isolates from the same animal species on different farms. Analysis of accessory (variable) genomes identified a virulence cassette associated previously with cystitis and neonatal meningitis that was only present in isolates from humans. Screening all 1948 isolates for accessory genes encoding antibiotic resistance revealed 41 different genes present in variable proportions of humans and livestock isolates. We identified a low prevalence of shared antimicrobial resistance genes between livestock and humans based on analysis of mobile genetic elements and long-read sequencing. We conclude that in this setting, there was limited evidence to support the suggestion that antimicrobial resistant pathogens that cause serious infection in humans originate from livestock.

Importance

The increasing prevalence ofE. colibloodstream infections is a serious public health problem. We used genomic epidemiology in a One Health study conducted in the East of England to examine putative sources ofE. coliassociated with serious human disease.E. colifrom 1517 patients with bloodstream infection were compared with 431 isolates from livestock farms and meat. Livestock-associated and bloodstream isolates were genetically distinct populations based on core genome and accessory genome analyses. Identical antimicrobial resistance genes were found in livestock and human isolates, but there was little overlap in the mobile elements carrying these genes. In addition, a virulence cassette found in humans isolates was not identified in any livestock-associated isolate. Our findings do not support the idea thatE. colicausing invasive disease or their resistance genes are commonly acquired from livestock.
Effects of radiofrequency electromagnetic radiation (RF-EMF) on honey bee queen development and mating success
Authors: Odemer Richard , Odemer Franziska
Published: October 2018

Mobile phones can be found almost everywhere across the globe, upholding a direct point-to-point connection between the device and the broadcast tower. The emission of radiofrequency electromagnetic radiation (RF-EMF) puts the surrounding environment inevitably into contact with this pollutant. We have therefore exposed honey bee queen larvae to the radiation of a common mobile phone device (GSM) during all stages of their pre-adult development including pupation. After 14 days of exposure, hatching of adult queens was assessed and mating success after further 11 days, respectively. Moreover, full colonies were established of five of the untreated and four of the treated queens to contrast population dynamics. We found that mobile phone radiation had significantly reduced the hatching ratio but not the mating success. If treated queens were successfully mated, colony development was not adversely affected. We provide evidence that RF-EMF only acts detrimental within the sensitivity of pupal development, once succeeded this point, no further impairment has manifested in adulthood. Our results are discussed against the background of long-lasting consequences for colony performance and the possible implication on periodic colony losses.

HIGHLIGHTS

Chronic RF-EMF exposure significantly reduced hatching of honey bee queens

Mortalities occurred during pupation, not at the larval stages

Mating success was not adversely affected by the irradiation

After the exposure, surviving queens were able to establish intact colonies

GRAPHICAL ABSTRACT
The promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 primate-specific endogenous retrovirus: an evolutionary connection between immunity and cognition
Authors: Nataf Serge , Uriagereka Juan , Benitez-Burraco Antonio
Published: October 2018

Social behavior and neuronal connectivity in rodents have been shown to be shaped by the prototypical T lymphocyte-derived pro-inflammatory cytokine Interferon-gamma (IFNγ). It has also been demonstrated that STAT1 (Signal Transducer And Activator Of Transcription 1), a transcription factor (TF) crucially involved in the IFNγ pathway, binds consensus sequences that, in humans, are located with a high frequency in the LTRs (Long Terminal Repeats) of the MER41 family of primate-specific HERVs (Human Endogenous Retrovirus). However, the putative role of an IFNγ/STAT1/MER41 pathway in human cognition and/or behavior is still poorly documented. Here, we present evidence that the promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 HERVs. This observation is specific to MER41 among more than 130 HERVs examined. Moreover, we have not found such a significant enrichment in the promoter regions of genes that associate with autism spectrum disorder (ASD) or schizophrenia. Interestingly, ID-associated genes exhibit promoter-localized MER41 LTRs that harbor TF binding sites (TFBSs) for not only STAT1 but also other immune TFs such as, in particular, NFKB1 (Nuclear Factor Kappa B Subunit 1) and STAT3 (Signal Transducer And Activator Of Transcription 3). Moreover, IL-6 (Interleukin 6) rather than IFNγ, is identified as the main candidate cytokine regulating such an immune/MER41/cognition pathway. Of note, functionally-relevant differences between humans and chimpanzees are observed regarding the 3 main components of this pathway: i) the protein sequences of immunes TFs binding MER41 LTRs, ii) the insertion sites of MER41 LTRs in the promoter regions of ID-associated genes and iii) the protein sequences of the targeted ID-associated genes. Finally, a survey of the human proteome has allowed us to map a protein-protein network which links the identified immune/MER41/cognition pathway to FOXP2 (Forkhead Box P2), a key TF involved in the emergence of human speech. Together, these results suggest that the stepped self-domestication of MER41 in the genomes of primates could have been a driver of cognitive evolution. Our data further indicate that non-inherited forms of ID might result from alterations of the immune/MER41/cognition pathway induced notably by the untimely or quantitatively inappropriate exposure of human neurons to IL-6.
Modeling visual performance differences with polar angle: A computational observer approach
Authors: Kupers Eline R. , Carrasco Marisa , Winawer Jonathan
Published: October 2018

Visual performance depends on polar angle, even when eccentricity is held constant; on many psychophysical tasks observers perform best when stimuli are presented on the horizontal meridian, worst on the upper vertical, and intermediate on the lower vertical meridian. This variation in performance ‘around’ the visual field can be as pronounced as that of doubling the stimulus eccentricity. The causes of these asymmetries in performance are largely unknown. Some factors in the eye, e.g. cone density, are positively correlated with the reported variations in visual performance with polar angle. However, the question remains whether such correlations can quantitatively explain the perceptual differences observed ‘around’ the visual field. To investigate the extent to which the earliest stages of vision –optical quality and cone density- contribute to performance differences with polar angle, we created a computational observer model. The model uses the open-source software package ISETBIO to simulate an orientation discrimination task for which visual performance differs with polar angle. The model starts from the photons emitted by a display, which pass through simulated human optics with fixational eye movements, followed by cone isomerizations in the retina. Finally, we classify stimulus orientation using a support vector machine to learn a linear classifier on the photon absorptions. To account for the 30% increase in contrast thresholds for upper vertical compared to horizontal meridian, as observed psychophysically on the same task, our computational observer model would require either an increase of ~7 diopters of defocus or a reduction of 500% in cone density. These values far exceed the actual variations as a function of polar angle observed in human eyes. Therefore, we conclude that these factors in the eye only account for a small fraction of differences in visual performance with polar angle. Substantial additional asymmetries must arise in later retinal and/or cortical processing.

Author Summary

A fundamental goal in computational neuroscience is to link known facts from biology with behavior. Here, we considered visual behavior, specifically the fact that people are better at visual tasks performed to the left or right of the center of gaze, compared to above or below at the same distance from gaze. We sought to understand what aspects of biology govern this fundamental pattern in visual behavior. To do so, we implemented a computational observer model that incorporates known facts about the front end of the human visual system, including optics, eye movements, and the photoreceptor array in the retina. We found that even though some of these properties arecorrelatedwith performance, they fall far short ofquantitatively explaining it. We conclude that later stages of processing in the nervous system greatly amplify small differences in the way the eye samples the visual world, resulting in strikingly different performance around the visual field.
Investigating the relationship between insecticide resistance, underlying molecular mechanisms and malaria prevalence in Anopheles gambiae s.l. from Guinea
Authors: Collins Emma , Vaselli Natasha M. , Sylla Moussa , Beavogui Abdoul H. , Orsborne James , Walker Thomas , Messenger Louisa A.
Published: October 2018

The threat of insecticide resistance across sub-Saharan Africa is anticipated to severely impact the continued effectiveness of malaria vector control. We investigated the effect of carbamate and pyrethroid resistance on Anopheles gambiae s.l age, Plasmodium falciparum infection and characterized molecular resistance mechanisms in Guinea. Pyrethroid resistance was intense, with survivors of ten times the insecticidal concentration required to kill susceptible individuals. The L1014F kdr allele was significantly associated with mosquito survival following deltamethrin or permethrin treatment (p=0.003 and p=0.04, respectively). N1575Y and I1527T mutations were identified in 13% and 10% of individuals, respectively, but neither conferred increased pyrethroid tolerance. Partial restoration of pyrethroid susceptibility following synergist pre-exposure suggest a role for mixed-function oxidases. Carbamate resistance was lower and significantly associated with the G119S Ace-1 mutation (p=0.001). Oocyst rates were 6.8% and 4.2% among resistant and susceptible mosquitoes, respectively; survivors of bendiocarb exposure were significantly more likely to be infected (p=0.03). Resistant mosquitoes had significantly lower parity rates; however, a subset of intensely pyrethroid-resistant vectors were more likely to be parous (p=0.042 and p=0.045, for survivors of five and ten times the diagnostic dose of insecticides, respectively). Our findings emphasize the need for additional studies directly assessing the influence of insecticide resistance on mosquito fitness.
Design of an epitope-based peptide vaccine againstCryptococcus neoformans
Authors: Khalil Isra , Omer Ibtihal , Farh Islam Zainalabdin Abdalgadir , Mohamed Hanaa Abdalla , Elsharif Hajr Abdallha , Mohamed ALazza Abdalla Hassan , Awad-Elkareem Mawadda Abd-Elraheem , Salih Mhamed Ahmed
Published: October 2018

Introduction

This study aimed to design an immunogenic epitope for Cryptococcus neoformans the etiological agent of cryptococcosis using in silico simulations, for epitope prediction, we selected the mannoprotein antigen MP88 which it’s known to induce protective immunity.

Material & method

A total of 39 sequences of MP88 protein with length 378 amino acids were retrieved from the National Center for Biotechnology Information database (NCBI) in the FASTA format were used to predict antigenic B-cell and T cell epitopes via different bioinformatics tools at Immune Epitope Database and Analysis Resource (IEDB). The tertiary structure prediction of MP88 was created in RaptorX, and visualized by UCSF Chimera software.

Result

A Conserved B-cell epitopesAYSTPA, AYSTPAS, PASSNCK, and DSAYPPhave displayed the most promising B cell epitopes. While theYMAADQFCL, VSYEEWMNYandFQQRYTGTFthey represent the best candidates T-cell conserved epitopes, the 9-mer epitopeYMAADQFCLdisplay the greater interact with 9 MHC-I alleles and HLA-A*02:01 alleles have the best interaction with an epitope. TheVSYEEWMNYandFQQRYTGTFthey are non-allergen whileYMAADQFCLwas an allergen. For MHC class II peptide binding prediction, theYARLLSLNA, ISYGTAMAVandINQTSYARLrepresent the most Three highly binding affinity core epitopes. The core epitopeINQTSYARLwas found to interact with 14 MHC-II. The allergenicity prediction revealsISYGTAMAV, INQTSYARLwere non-allergen andYARLLSLNAwas an allergen. Regarding population coverage theYMAADQFCLexhibit, a higher percentage among the world (69.75%) and the average population coverage was93.01%.In MHC-II,ISYGTAMAVepitope reveal a higher percentage (74.39%) and the average population coverage was (81.94%). This successfully designed a peptide vaccine against Cryptococcus neoformans open up a new horizon in Cryptococcus neoformans research; the results require validation by in vitro and in vivo experiments.
Cannabichromene is a cannabinoid CB2 receptor agonist
Authors: Udoh Michael , Santiago Marina , Devenish Steven , McGregor Iain S. , Connor Mark
Published: October 2018

BACKGROUND

Cannabichromene (CBC) is one of the most abundant phytocannabinoids inCannabis spp. It has modest anti-nociceptive and anti-inflammatory effects and potentiates some effects of Δ9-tetrahydrocannabinol (THC)in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at CB1 and CB2 receptors.

EXPERIMENTAL APPROACH

AtT20 cells stably expressing HA-tagged human CB1 and CB2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed.

KEY RESULTS

CBC activated CB2 but not CB1 receptors to produce a hyperpolarization of AtT20 cells. Activation of CB2 receptors was antagonised by the CB2 antagonist AM630 and sensitive to pertussis toxin. Co-application of CBC reduced activation of CB2 receptors CP55,940, a potent CB1 and CB2 agonist. Continuous CBC application induced loss of cell surface CB2 receptors and desensitisation of the CB2-induced hyperpolarization.

CONCLUSIONS AND IMPLICATIONS

Cannabichromene is a selective CB2 receptor agonist displaying higher efficacy than THC in hyperpolarising AtT20 cells. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB2-mediated modulation of inflammation.