bluuebunny/crossref_metadata_2025 huggingface dataset:
Internalized HIV Stigma Is Associated With Concurrent Viremia and Poor Retention in a Cohort of US Patients in HIV Care
Authors: Christopoulos Katerina A. , Neilands Torsten B. , Hartogensis Wendy , Geng Elvin H. , Sauceda John , Mugavero Michael J. , Crane Heidi M. , Fredericksen Rob J. , Moore Richard D. , Mathews William Christopher , Mayer Kenneth H. , Chander Geetanjali , Hurt Christopher B. , Johnson Mallory O.
Published: June 2019

Background:

The relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data.

Setting:

Center for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study.

Methods:

Beginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment.

Results:

Of 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17).

Conclusions:

Higher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.
Marijuana Use and Its Associations With Pain, Opioid Dose, and HIV Viral Suppression Among Persons Living With HIV on Chronic Opioid Therapy
Authors: Merlin Jessica S. , Samet Jeffrey H. , Cheng Debbie M. , Lira Marlene C. , Tsui Judith I. , Forman Leah S. , Colasanti Jonathan , Walley Alexander Y. , Del Rio Carlos , Liebschutz Jane M.
Published: June 2019

Background:

Medical marijuana is legal in 29 US states and the District of Columbia: both HIV and chronic pain are “approved conditions” for receipt. Chronic pain is common among people living with HIV (PLWH). We anticipate PLWH will question their providers about medical marijuana for chronic pain. We examined marijuana use and its associations with pain, opioid dose, and HIV viral suppression among PLWH receiving chronic opioid therapy.

Methods:

PLWH prescribed chronic opioid therapy were recruited into the Targeting Effective Analgesia in Clinics for HIV cohort. The main exposure variable was any past 12-month marijuana use. The primary outcomes were (1) opioid misuse (≥9 on the Current Opioid Misuse Measure) and (2) opioid dose (morphine equivalent daily dose). HIV viral load (VL) suppression (<200 copies/μL) and pain severity and interference using the Brief Pain Inventory were exploratory outcomes.

Results:

Participants (n = 166) were men (65%), Black (72%), and had an undetectable VL (89%). We found no significant association between current marijuana use and opioid misuse, opioid dose, or pain. Current marijuana use was associated with 3.03 times the odds of having a detectable VL (95% odds ratio: 1.11–8.31, P = 0.03) while controlling for depressive symptoms and other substance use.

Discussion:

We did not detect an association between marijuana use and opioid misuse behaviors, opioid dose, or pain. In an exploratory analysis, current marijuana use was associated with 3× greater odds of having a detectable VL. This study provides insights into potential consequences of marijuana use among PLWH with chronic pain.
Perlin Noise Generation of Physiologically Realistic Patterns of Fibrosis
Authors: Jakes David , Burrage Kevin , Drovandi Christopher C. , Burrage Pamela , Bueno-Orovio Alfonso , Santos Rodrigo Weber dos , Rodriguez Blanca , Lawson Brodie A. J.
Published: June 2019

Fibrosis, the pathological excess of fibroblast activity, is a significant health issue that hinders the function of many organs in the body, in some cases fatally. However, the severity of fibrosis-derived conditions depends on both the positioning of fibrotic affliction, and the microscopic patterning of fibroblast-deposited matrix proteins within afflicted regions. Variability in an individual’s manifestation of a type of fibrosis is an important factor in explaining differences in symptoms, optimum treatment and prognosis, but a need forex vivoprocedures and a lack of experimental control over conflating factors has meant this variability remains poorly understood. In this work, we present a computational methodology for the generation of patterns of fibrosis microstructure, demonstrating the technique using histological images of four types of cardiac fibrosis. Our generator and automated tuning method prove flexible enough to capture each of these very distinct patterns, allowing for rapid generation of new realisations for high-throughput computational studies. We also demonstrate via simulation, using the generated fibrotic patterns, the importance of micro-scale variability by showing significant differences in electrophysiological impact even within a single class of fibrosis.
BiSCoT: Improving large eukaryotic genome assemblies with optical maps
Authors: Istace Benjamin , Belser Caroline , Aury Jean-Marc
Published: June 2019

Motivation

Long read sequencing and Bionano Genomics optical maps are two techniques that, when used together, make it possible to reconstruct entire chromosome or chromosome arms structure. However, the existing tools are often too conservative and organization of contigs into scaffolds is not always optimal.

Results

We developed BiSCoT (Bionano SCaffolding COrrection Tool), a tool that post-processes files generated during a Bionano scaffolding in order to produce an assembly of greater contiguity and quality. BiSCoT was tested on a human genome and four publicly available plant genomes sequenced with Nanopore long reads and improved significantly the contiguity and quality of the assemblies. BiSCoT generates a fasta file of the assembly as well as an AGP file which describes the new organization of the input assembly.

Availability

BiSCoT and improved assemblies are freely available on Github at http://www.genoscope.cns.fr/biscot and Pypi at https://pypi.org/project/biscot/.
A classification framework forBacillus anthracisdefined by global genomic structure
Authors: Bruce Spencer A. , Schiraldi Nicholas J. , Kamath Pauline L. , Easterday W. Ryan , Turner Wendy C.
Published: June 2019

Bacillus anthracis, the causative agent of anthrax, is a considerable global health threat affecting wildlife, livestock, and the general public. In this study whole-genome sequence analysis of over 350B. anthracisisolates was used to establish a new high-resolution global genotyping framework that is both biogeographically informative, and compatible with multiple genomic assays. The data presented in this study shed new light on the diverse global dissemination of this species and indicate that many lineages may be uniquely suited to the geographic regions in which they are found. In addition, we demonstrate that plasmid genomic structure for this species is largely consistent with chromosomal population structure, suggesting vertical inheritance in this bacterium has contributed to its evolutionary persistence. This classification methodology is the first based on population genomic structure for this species and has potential use for local and broader institutions seeking to understand both disease outbreak origins and recent introductions. In addition, we provide access to a newly developed genotyping script as well as the full whole genome sequence analyses output for this study, allowing future studies to rapidly employ and append their data in the context of this global collection. This framework may act as a powerful tool for public health agencies, wildlife disease laboratories, and researchers seeking to utilize and expand this classification scheme for further investigations intoB. anthracisevolution.
Does alpha phase modulate visual target detection? Three experiments with tACS phase-based stimulus presentation
Authors: de Graaf Tom A. , Thomson Alix , Janssens Shanice E.W. , van Bree Sander , ten Oever Sanne , Sack Alexander T.
Published: June 2019

In recent years the influence of alpha (7-13 Hz) phase on visual processing has received a lot of attention. Magneto-/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. If occipital alpha phase is functionally relevant, the phase of occipital alpha-frequency transcranial alternating current stimulation (tACS) could modulate visual processing. Visual stimuli presented at different pre-determined, experimentally controlled, phases of the entraining tACS signal should then result in an oscillatory pattern of visual performance. We studied this in a series of experiments. In experiment one, we applied 10 Hz tACS to right occipital cortex (O2) and used independent psychophysical staircases to obtain contrast thresholds for detection of visual gratings in left or right hemifield, in six equidistant tACS phase conditions. In experiments two and three, tACS was at EEG-based individual peak alpha frequency. In experiment two, we measured detection rates for gratings with (pseudo-)fixed contrast levels. In experiment three, participants detected brief luminance changes in a custom-built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one-cycle sinusoid as predicted. However, post-hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT in both experiments 1 and 2 (not measured in experiment 3). This observation is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.
Precise transcription timing by a second-messenger drives a bacterial G1/S cell cycle transition
Authors: Kaczmarczyk Andreas , Hempel Antje M. , von Arx Christoph , Böhm Raphael , Dubey Badri N. , Nesper Jutta , Schirmer Tilman , Hiller Sebastian , Jenal Urs
Published: June 2019

Bacteria adapt their growth rate to their metabolic status and environmental conditions by modulating the length of their quiescent G1 period. But the molecular mechanisms controlling G1 length and exit from G1 are poorly understood. Here we identify a key role for the second messenger c-di-GMP, and demonstrate that a gradual increase in c-di-GMP concentration determines precise gene expression during G1/S inCaulobacter crescentus. We show that c-di-GMP strongly stimulates the kinase ShkA, activates the TacA transcription factor, and initiates a G1/S-specific transcription program leading to cell morphogenesis and S-phase entry. C-di-GMP activates ShkA by binding to its central pseudo-receiver domain uncovering this wide-spread domain as a novel signal input module of bacterial kinases. Activation of the ShkA-dependent genetic program also causes c-di-GMP to reach peak levels, which triggers S-phase entry and, in parallel, promotes proteolysis of ShkA and TacA. Thus, a gradual increase of c-di-GMP results in a precisely tuned ShkA-TacA activity window enabling G1/S specific gene expression before cells commit to replication initiation. By defining a regulatory mechanism for G1/S control, this study contributes to understanding bacterial growth control at the molecular level.

GRAPHICAL ABSTRACT
A live-cell screen for altered Erk dynamics reveals principles of proliferative control
Authors: Goglia Alexander G. , Wilson Maxwell Z. , Silbert Jillian , Basta Lena P. , Jena Siddhartha G. , Devenport Danelle , Toettcher Jared E.
Published: June 2019

Complex, time-varying responses have been observed widely in cell signaling, but how specific dynamics are generated or regulated is largely unknown. One major obstacle has been that high-throughput screens for identifying pathway components are typically incompatible with the live-cell assays used to monitor dynamics. Here, we address this challenge by performing a drug screen for altered Erk signaling dynamics in primary mouse keratinocytes. We screened a library of 429 kinase inhibitors, monitoring Erk activity over 5 h in more than 80,000 single live cells. The screen revealed both known and uncharacterized modulators of Erk dynamics, including inhibitors of non-EGFR receptor tyrosine kinases (RTKs) that increased Erk pulse frequency and overall activity. Using drug treatment and direct optogenetic control, we demonstrate that drug-induced changes to Erk dynamics alter the conditions under which cells proliferate. Our work opens the door to high-throughput screens using live-cell biosensors and reveals that cell proliferation integrates information from Erk dynamics as well as additional permissive cues.
Tailoring cryo-electron microscopy grids by photo-micropatterning for in-cell structural studies
Authors: Toro-Nahuelpan Mauricio , Zagoriy Ievgeniia , Senger Fabrice , Blanchoin Laurent , Théry Manuel , Mahamid Julia
Published: June 2019

Spatially-controlled cell adhesion on electron microscopy (EM) supports remains a bottleneck in specimen preparation for cellular cryo-electron tomography. Here, we describe contactless and mask-free photo-micropatterning of EM grids for site-specific deposition of extracellular matrix-related proteins. We attained refined cell positioning for micromachining by cryo-focused ion beam milling. Complex patterns generated predictable intracellular organization, allowing direct correlation between cell architecture and in-cell 3D-structural characterization of the underlying molecular machinery.
Multimodal fusion of structural and functional brain imaging in depression using linked independent component analysis
Authors: Maglanoc Luigi A. , Kaufmann Tobias , Jonassen Rune , Hilland Eva , Beck Dani , Landrø Nils Inge , Westlye Lars T.
Published: June 2019

Background

Previous structural and functional neuroimaging studies have implicated distributed brain regions and networks in depression. However, there are no robust imaging biomarkers that are specific to depression, which may be due to clinical heterogeneity and neurobiological complexity. A dimensional approach and fusion of imaging modalities may yield a more coherent view of the neuronal correlates of depression.

Methods

We used linked independent component analysis to fuse cortical macrostructure (thickness, area, gray matter density), white matter diffusion properties and resting-state fMRI default mode network amplitude in patients with a history of depression (n = 170) and controls (n = 71). We used univariate and machine learning approaches to assess the relationship between age, sex, case-control status, and symptom loads for depression and anxiety with the resulting brain components.

Results

Univariate analyses revealed strong associations between age and sex with mainly global but also regional specific brain components, with varying degrees of multimodal involvement. In contrast, there were no significant associations with case-control status, nor symptom loads for depression and anxiety with the brain components, nor any interaction effects with age and sex. Machine learning revealed low model performance for classifying patients from controls and predicting symptom loads for depression and anxiety, but high age prediction accuracy.

Conclusion

Multimodal fusion of brain imaging data alone may not be sufficient for dissecting the clinical and neurobiological heterogeneity of depression. Precise clinical stratification and methods for brain phenotyping at the individual level based on large training samples may be needed to parse the neuroanatomy of depression.
Basal forebrain volume reliably predicts the cortical spread of Alzheimer’s degeneration
Authors: Fernández-Cabello Sara , Kronbichler Martin , Dijk Koene R. A. Van , Goodman James A. , Spreng R. Nathan , Schmitz Taylor W. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2019

Alzheimer’s disease neuropathology is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model posits that Alzheimer’s neurodegeneration starts in the entorhinal cortices, before spreading to temporoparietal cortex. Challenging this model, we previously provided evidence that degeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, precedes and predicts entorhinal degeneration (Schmitz and Spreng, 2016). There have been few systematic attempts at directly comparing staging models using in vivo longitudinal biomarker data, and determining if these comparisons generalize across independent samples. Here we addressed the sequence of pathological staging in Alzheimer’s disease using two independent samples of the Alzheimer’s Disease Neuroimaging Initiative (N1= 284;N2= 553) with harmonized CSF assays of amyloid (Aβ) and hyperphosphorylated tau (pTau), and longitudinal structural MRI data over two years. We derived measures of gray matter degeneration in a priori NbM and the entorhinal regions of interest. To examine the spreading of degeneration, we used a predictive modelling strategy which tests whether baseline gray matter volume in a seed region accounts for longitudinal change in a target region. We demonstrated that predictive pathological spread favored the NbM→entorhinal over the entorhinal→NbM model. This evidence generalized across the independent samples (N1:r=0.20,p=0.03;N2:r=0.37,p<0.001). We also showed that CSF concentrations of pTau/Aβ moderated the observed predictive relationship, consistent with evidence in rodent models of an underlying trans-synaptic mechanism of pathophysiological spread (t826=2.55,p=0.01). The moderating effect of CSF was robust to additional factors, including clinical diagnosis (t826=1.65,p=0.49). We then applied our predictive modelling strategy to an exploratory whole-brain voxel-wise analysis to examine the spatial specificity of the NbM→entorhinal model. We found that smaller baseline NbM volumes predicted greater degeneration in localized regions of the entorhinal and perirhinal cortices. By contrast, smaller baseline entorhinal volumes predicted degeneration in the medial temporal cortex, recapitulating the prevailing staging model. Our findings suggest that degeneration of the basal forebrain cholinergic projection system is a robust and reliable upstream event of entorhinal and neocortical degeneration, calling into question the prevailing view of Alzheimer’s disease pathogenesis.
Normative cerebral cortical thickness for human visual areas
Authors: Alvarez Ivan , Parker Andrew J. , Bridge Holly
Published: June 2019

1

Studies of changes in cerebral neocortical thickness often rely on small control samples for comparison with specific populations with abnormal visual systems. We present a normative dataset for FreeSurfer-derived cortical thickness across 25 human visual areas derived from 960 participants in the Human Connectome Project. Cortical thickness varies systematically across visual areas, in broad agreement with canonical visual system hierarchies in the dorsal and ventral pathways. In addition, cortical thickness estimates show consistent within-subject variability and reliability. Importantly, cortical thickness estimates in visual areas are well described by a normal distribution, making them amenable to direct statistical comparison.

Highlights

Normative neocortical thickness values for human visual areas measured with FreeSurfer

A gradient of increasing neocortical thickness with visual area hierarchy

Consistent within- and between-subject variability in neocortical thickness across visual areas
Does the neuronal noise in cortex help generalization?
Authors: Hu Brian , Shang Jiaqi , Iyer Ramakrishnan , Siegle Josh , Mihalas Stefan
Published: June 2019

One remarkable feature of neuronal activity in the mammalian cortex is the high level of variability in response to repeated stimuli. First, we used an open dataset, the Allen Brain Observatory, to quantify the distribution of responses to repeated presentations of natural movies. We find that even for their preferred moment in the movie clip, neurons have high variability which cannot be well captured by Gaussian or Poisson distributions. A large fraction of responses are better fit by log-normal or Gaussian mixture models with two components. These distributions are similar to activity distributions during training of deep neural networks using dropout. This poses the interesting hypothesis: is the role of cortical noise to help in generalization during learning?

Second, to ensure the robustness of our results we analyzed electrophysiological recordings in the same areas of mouse visual cortex, again using repeated natural movie presentations and found similar response distributions. To make sure that the trial-by-trial variations we observe are not due exclusively to the result of changes in state, we constructed a population coupling model, where each neuron’s activity is coupled to a low-dimension version of the activity of all other simultaneously recorded neurons. The population coupling model can capture global, brain-wide activity fluctuations that are state-dependent. The residuals from this model also show non-Gaussian noise distributions.

Third, we ask a more specific question: is the noise in the cortex more likely to move the representation of the stimulus in-class versus out-of-class? To address this question, we analyzed the responses of neurons across trials from multiple sections of different movie clips. We observe that the noise in the cortex better aligns to in-class variations. We argue that a useful noise for learning generalizations is to move from representations of different exemplars in-class, similar to cortical noise.
Computational and robotic modeling reveal parsimonious combinations of interactions between individuals in schooling fish
Authors: Lei Liu , Escobedo Ramón , Sire Clément , Theraulaz Guy
Published: June 2019

Coordinated motion and collective decision-making in fish schools result from complex interactions by which individuals integrate information about the behavior of their neighbors. However, little is known about how individuals integrate this information to take decisions and control their movements. Here, we combine experiments with computational and robotic approaches to investigate the impact of different strategies for a fish to interact with its neighbors on collective swimming in groups of rummy-nose tetra (Hemigrammus rhodostomus). By means of a data-based agent model describing the interactions between pairs ofH. rhodostomus(Caloviet al., 2018), we show that the simple addition of the pairwise interactions with two neighbors quantitatively reproduces the collective behavior observed in groups of five fish. Increasing the number of interacting neighbors does not significantly improve the simulation results. Remarkably, we find that groups remain cohesive and polarized even when each agent only interacts with only one of its neighbors: the one that has the strongest contribution to the heading variation of the focal agent. However, group cohesion is lost when each agent only interacts with its nearest neighbor. We then investigate by means of a swarm robotic platform the collective motion in groups of five robots. Our platform combines the implementation of the fish behavioral model and an engineering-minded control system to deal with real-world physical constraints. We find that swarms of robots are able to reproduce the behavioral patterns observed in groups of five fish when each robot only interacts with its neighbor having the strongest effect on its heading variation, whereas increasing the number of interacting neighbors does not significantly improve the group coordination. Overall, our results suggest that fish have to acquire only a minimal amount of information about their environment to coordinate their movements when swimming in groups.

Author Summary

How do fish combine and integrate information from multiple neighbors when swimming in a school? What is the minimum amount of information about their environment needed to coordinate their motion? To answer these questions, we combine experiments with computational and robotic modeling to test several hypotheses about how individual fish could combine and integrate the information on the behavior of their neighbors when swimming in groups. Our research shows that, for both simulated agents and robots, using the information of two neighbors is sufficient to qualitatively reproduce the collective motion patterns observed in groups of fish. Remarkably, our results also show that it is possible to obtain group cohesion and coherent collective motion over long periods of time even when individuals only interact with their most influential neighbor, that is, the one that exerts the most important effect on their heading variation.
Stochastic Modeling Reveals Kinetic Heterogeneity in Post-replication DNA Methylation
Authors: Busto-Moner Luis , Morival Julien , Fahim Arjang , Reitz Zachary , Downing Timothy L. , Read Elizabeth L.
Published: June 2019

DNA methylation is a heritable epigenetic modification that plays an essential role in mammalian development. Genomic methylation patterns are dynamically maintained, with DNA methyltransferases mediating inheritance of methyl marks onto nascent DNA over cycles of replication. A recently developed experimental technique employing immunoprecipitation of bromodeoxyuridine labeled nascent DNA followed by bisulfite sequencing (Repli-BS) measures post-replication temporal evolution of cytosine methylation, thus enabling genome-wide monitoring of methylation maintenance. In this work, we combine statistical analysis and stochastic mathematical modeling to analyze Repli-BS data from human embryonic stem cells. We estimate site-specific kinetic rate constants for the restoration of methyl marks on >10 million uniquely mapped cytosines within the CpG (cytosine-phosphate-guanine) dinucleotide context across the genome using Maximum Likelihood Estimation. We find that post-replication remethylation rate constants span approximately two orders of magnitude, with half-lives of per-site recovery of steady-state methylation levels ranging from shorter than ten minutes to five hours and longer. Furthermore, we find that kinetic constants of maintenance methylation are correlated among neighboring CpG sites. Stochastic mathematical modeling provides insight to the biological mechanisms underlying the inference results, suggesting that enzyme processivity and/or collaboration can produce the observed kinetic correlations. Our combined statistical/mathematical modeling approach expands the utility of genomic datasets and disentangles heterogeneity in methylation patterns arising from replication-associated temporal dynamics versus stable cell-to-cell differences.
Quantifying transmission of emerging zoonoses: Using mathematical models to maximize the value of surveillance data
Authors: Ambrose Monique R. , Kucharski Adam J. , Formenty Pierre , Muyembe-Tamfum Jean-Jacques , Rimoin Anne W. , Lloyd-Smith James O.
Published: June 2019

Understanding and quantifying the transmission of zoonotic pathogens is essential for directing public health responses, especially for pathogens capable of transmission between humans. However, determining a pathogen’s transmission dynamics is complicated by challenges often encountered in zoonotic disease surveillance, including unobserved sources of transmission (both human and zoonotic), limited spatial information, and unknown scope of surveillance. In this work, we present a model-based inference method that addresses these challenges for subcritical zoonotic pathogens using a spatial model with two levels of mixing. After demonstrating the robustness of the method using simulation studies, we apply the new method to a dataset of human monkeypox cases detected during an active surveillance program from 1982-1986 in the Democratic Republic of the Congo (DRC). Our results provide estimates of the reproductive number and spillover rate of monkeypox during this surveillance period and suggest that most human-to-human transmission events occur over distances of 30km or less. Taking advantage of contact-tracing data available for a subset of monkeypox cases, we find that around 80% of contact-traced links could be correctly recovered from transmission trees inferred using only date and location. Our results highlight the importance of identifying the appropriate spatial scale of transmission, and show how even imperfect spatiotemporal data can be incorporated into models to obtain reliable estimates of human-to-human transmission patterns.

Author Summary

Surveillance datasets are often the only sources of information about the ecology and epidemiology of zoonotic infectious diseases. Methods that can extract as much information as possible from these datasets therefore provide a key advantage for informing our understanding of the disease dynamics and improving our ability to choose the optimal intervention strategy. We developed and tested a likelihood-based inference method based on a mechanistic model of the spillover and human-to-human transmission processes. We first used simulated datasets to explore which information about the disease dynamics of a subcritical zoonotic pathogen could be successfully extracted from a line-list surveillance dataset with non-localized spatial information and unknown geographic coverage. We then applied the method to a dataset of human monkeypox cases detected during an active surveillance program in the Democratic Republic of the Congo between 1982 and 1986 to obtain estimates of the reproductive number, spillover rate, and spatial dispersal of monkeypox in humans.
Activation ofShigella flexneritype 3 secretion requires a host-induced conformational change to the translocon pore
Authors: Russo Brian C. , Duncan Jeffrey K. , Wiscovitch Alexandra L. , Hachey Austin C. , Goldberg Marcia B.
Published: June 2019

Type 3 secretion systems (T3SSs) are conserved bacterial nanomachines that inject virulence proteins (effectors) into eukaryotic cells during infection. Due to their ability to introduce heterologous protein into human cells, these systems are being developed as therapeutic delivery devices. The T3SS assembles a translocon pore in the plasma membrane and then docks onto the pore. Docking activates effector secretion through the pore and into the host cytosol. Here, usingShigella flexneri, a model pathogen for the study of type 3 secretion, we determined the molecular mechanisms by which host intermediate filaments trigger docking and enable effector secretion. We show that the interaction of intermediate filaments with the translocon pore protein IpaC changed the pore’s conformation in a manner that was required for docking. Intermediate filaments repositioned residues of theShigellapore protein IpaC that are located on the surface of the pore and in the pore channel. Restricting these conformational changes blocked docking in an intermediate filament-dependent manner. These data demonstrate that a host-induced conformational change to the pore enables T3SS docking and effector secretion, providing new mechanistic insight into the regulation of type 3 secretion.

Author summary

The movement of bacterial proteins across membranes is essential for bacterial physiology and bacterial virulence. The type 3 secretion system moves bacterial virulence proteins from the inside of bacterial pathogens into human cells. To do so, the type 3 secretion system forms a pore in the plasma membrane of the target cell, attaches (docks) onto the pore, and delivers virulence proteins through the pore. Docking is essential for establishing a continuous channel from the inside of the bacteria to the inside of the human cell. What enables the type 3 secretion system to dock onto pores is not understood. We show that structural proteins in human cells, intermediate filament proteins, induce structural rearrangements to the type 3 secretion pore that trigger docking and that enable the subsequent delivery of virulence proteins into human cells. Due to the wide prevalence of type 3 secretion systems among human pathogens, these findings are likely to broadly enhance our understanding of type 3 secretion.
Controlling Strawberry Mites: Comparison of New Bio-Pesticides and Conventional Chemical Pesticides
Authors: Zhu Jiahong , Li Zhuo , Ren Zongjie , Cao Aocheng , Yan Dongdong , Wang Qiuxia , Ouyang Canbin , Li Yuan
Published: June 2019

BACKGROUND

Tetranychus cinnabarinusis one of the pest insects most severely influencing strawberry production. It has a high attack rate and causes severe economic losses. Laboratory toxicity tests and greenhouse experiments were carried out using 13 acaricides to determine their efficacy and potential mechanisms of action.

RESULTS

Abamectin showed the highest efficacy againstT. cinnabarinusfemale mites; its LC50value was 0.18mg L-1. Pyridaben, cyhalothrin, veratrine, and carbosulfan showed reasonably high efficacy; their LC50values were 2.69 mg L-1, 3.94 mg L-1, 5.98 mg L-1, and 6.75 mg L-1, respectively. Less effective were hexythiazox and bifenthrin, their LC50values were 9.82 mg L-1and 19.09 mg L-1, respectively. Other acaricides such as spirodiclofen, chlorantraniliprole, chlorfenapyr, spinosad, and bifenazate did not show good efficacy. The status of female mites treated with avermectin, pyridaben, kanghebio and cyhalothrin changed significantly under a fluorescence microscope. There were no significant differences among female mites treated with spirotetramat, chlorantraniliprole, spinosad and bifenazate. Enzyme activity tests showed that Kanghebio and cyhalothrin obviously inhibited Ca2+-adenosine triphosphatase (Ca2+-ATPase), while veratrine and kanghebi obviously inhibited acetylcholinesterase (TChE) and monoamine oxidase (MAO). Cyhalothrinexerted an auxo-action on MAO. Greenhouse experiment indicated that abamectin showed the best efficacy, as well as the longest duration of efficacy, pyridaben, cyhalothrin, veratrine, and kanghebio followed, while carbosulfan, hexythiazox, and bifenthrin performed the worst.

CONCLUSIONS

Our study provided a scientific basis for chemical pesticides to be replaced by these and potentially other new bio-pesticides.
Chronic Repeated Predatory Stress Induces Resistance to Quinine Adulteration of Ethanol in Male Mice
Authors: Shaw Gladys A. , Bent Maria Alexis M. , Council Kimaya R. , Pais A. Christian , Amstadter Ananda , Wolstenholme Jennifer T. , Miles Michael F. , Neigh Gretchen N.
Published: June 2019

Background

Trauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic repeated predatory stress (CRPS) to query the extent to which sex interacts with CRPS to influence alcohol consumption, or cessation of consumption.

Methods

Male (n=16) and female (n=15) C57BL/6J mice underwent CRPS or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). Following the conclusion of two rounds of repeated stress, behavior was assessed in the open field. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) assessment (P90-131) with the options of 20% ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess the drinking response to adulteration of the alcohol.

Results

CRPS increased fecal corticosterone concentrations and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS reduced alcohol aversion in male mice such that higher concentrations of quinine were necessary to reduce alcohol intake as compared to control mice. CRPS did not alter alcohol-related behaviors in female mice.

Conclusion

Collectively, we demonstrate that repeated CRPS can induce anxiety-like behavior in both sexes but selectively influences the response to ethanol adulteration in males.
Atypical MEG inter-subject correlation during listening to continuous natural speech in dyslexia
Authors: Thiede A. , Glerean E. , Kujala T. , Parkkonen L.
Published: June 2019

Listening to speech elicits brain activity time-locked to the speech sounds. This so-called neural entrainment to speech was found to be atypical in dyslexia, a reading impairment associated with neural speech processing deficits. We hypothesized that the brain responses of dyslexic vs. normal readers to real-life speech would be different, and thus the strength of inter-subject correlation (ISC) would differ from that of typical readers and be reflected in reading-related measures.

We recorded magnetoencephalograms (MEG) of 23 dyslexic and 21 typically-reading adults during listening to ∼10 min of natural Finnish speech consisting of excerpts from radio news, a podcast, a self-recorded audiobook chapter and small talk. The amplitude envelopes of band-pass-filtered MEG source signals were correlated between subjects in a cortically-constrained source space in six frequency bands. The resulting ISCs of dyslexic and typical readers were compared with a permutation-based t-test. Neuropsychological measures of phonological processing, technical reading, and working memory were correlated with the ISCs utilizing the Mantel test.

During listening to speech, ISCs were reduced in dyslexic compared to typical readers in delta (0.5–4 Hz), alpha (8–12 Hz), low gamma (25–45 Hz) and high gamma (55–90 Hz) frequency bands. In the beta (12–25 Hz) band, dyslexics had mainly enhanced ISC to speech compared to controls. Furthermore, we found that ISCs across both groups were associated with phonological processing, technical reading, and working memory.

The atypical ISC to natural speech in dyslexics supports the temporal sampling deficit theory of dyslexia. It also suggests over-synchronization to phoneme-rate information in speech, which could indicate more effort-demanding sampling of phonemes from speech in dyslexia. These irregularities in parsing speech are likely some of the complex neural factors contributing to dyslexia. The associations between neural coupling and reading-related skills further support this notion.

Research Highlights

MEG inter-subject correlation (ISC) of dyslexics was atypical while listening to speech.

Depending on the frequency band, dyslexics had stronger or weaker ISC than controls.

Reading-related measures correlated with the strength of ISC.
Mobile phones: The effect of its presence on learning and memory
Authors: Tanil Clarissa T. , Yong Min Hooi
Published: June 2019

Our aim was to examine the effect of mobile phone’s presence on learning and memory among undergraduates. A total of 119 undergraduates completed a memory task and the Smartphone Addiction Scale (SAS). As predicted, those without phones had higher recall accuracy compared to those with phones. Results showed a significant negative relationship between phone conscious thought and memory recall but not for SAS and memory recall. Phone conscious thought significantly predicted memory accuracy. We found that the presence of a phone and high phone conscious thought affects one’s memory learning and recall, indicating the negative effect of a mobile phone proximity to our learning and memory.
The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae ofEquus caballus
Authors: Armstrong Caitlin , Cassimeris Lynne , Silva Santos Claire Da , Micoogullari Yagmur , Wagner Bettina , Babasyan Susanna , Brooks Samantha , Galantino-Homer Hannah
Published: June 2019

The equine hoof inner epithelium is folded into primary and secondary epidermal lamellae which increase the dermo-epidermal junction surface area of the hoof and can be affected by laminitis, a common disease of equids. Two keratin proteins (K), K42 and K124, are the most abundant keratins in the hoof lamellar tissue ofEquus caballus. We hypothesize that these keratins are lamellar tissue-specific and could serve as differentiation- and disease-specific markers. Our objective was to characterize the expression of K42 and K124 in equine stratified epithelia and to generate monoclonal antibodies against K42 and K124. By RT-PCR analysis, keratin gene (KRT)KRT42andKRT124expression was present in lamellar tissue, but not cornea, haired skin, or hoof coronet. In situ hybridization studies showed thatKRT124localized to the suprabasal and, to a lesser extent, basal cells of the lamellae, was absent from haired skin and hoof coronet, and abruptly transitions fromKRT124-negative coronet toKRT124-positive proximal lamellae. A monoclonal antibody generated against full-length recombinant equine K42 detected a lamellar keratin of the appropriate size, but also cross-reacted with other epidermal keratins. Three monoclonal antibodies generated against N- and C-terminal K124 peptides detected a band of the appropriate size in lamellar tissue and did not cross-react with proteins from haired skin, corneal limbus, hoof coronet, tongue, glabrous skin, oral mucosa, or chestnut on immunoblots. K124 localized to lamellar cells by indirect immunofluorescence. This is the first study to demonstrate the localization and expression of a hoof lamellar-specific keratin, K124, and to validate anti-K124 monoclonal antibodies.
Plant-mediated community structure of spring-fed, coastal rivers
Authors: Lauretta Matthew V. , Pine William E. , Walters Carl J. , Frazer Thomas K.
Published: June 2019

Quantifying ecosystem-level processes that drive community structure and function is key to the development of effective environmental restoration and management programs. To assess the effects of large-scale aquatic vegetation loss on fish and invertebrate communities in Florida estuaries, we quantified and compared the food webs of two adjacent spring-fed rivers that flow into the Gulf of Mexico. We constructed a food web model using field-based estimates of community absolute biomass and trophic interactions of a highly productive vegetated river, and modeled long-term simulations of vascular plant decline coupled with seasonal production of filamentous macroalgae. We then compared ecosystem model predictions to observed community structure of the second river that has undergone extensive vegetative habitat loss, including extirpation of several vascular plant species. Alternative models incorporating bottom-up regulation (decreased primary production resulting from plant loss) versus coupled top-down effects (compensatory predator search efficiency) were ranked by goodness-of-fit tests of model predictions to the empirical community observations. Our best model for predicting community responses to vascular plant loss incorporated coupled effects of decreased primary production (bottom-up), increased prey search efficiency of large-bodied fishes at low vascular plant density (top-down), and decreased prey search efficiency of small-bodied fishes with increased biomass of filamentous macroalgae (bottom-up). The results of this study indicate that the loss of vascular plants from the coastal river ecosystem may alter the food web structure and result in a net decline in the biomass of fishes. These results are highly relevant to ongoing landscape-level restoration programs intended to improve aesthetics and ecosystem function of coastal spring-fed rivers by highlighting how the structure of these communities can be regulated both by resource availability and consumption. Restoration programs will need to acknowledge and incorporate both to be successful.
An integrated solution for space shuttle launching ramp
Authors: Yücenur G. Nilay , Subaşı Anıl Sezer
Published: June 2019

Purpose

The purpose of this study is to select the most appropriate city in Turkey for space shuttle launching ramp.

Design/methodology/approach

In the proposed approach, an integrated methodology is used. The SWARA method is used in the first phase of the solution for determining criteria’s importance weights. Based on the criteria weights obtained by the SWARA method, the WASPAS method is used for selecting the best alternative.

Findings

Mugla is selected for the most suitable city for the first space shuttle launching pad according to determined criteria and proposed model.

Research limitations/implications

Although there are 81 cities in Turkey, 4 alternatives were selected for evaluation. It is possible to eliminate this limitation by the future studies with the implementation of proposed model to entire of Turkey.

Practical implications

This proposed model can be used by the countries which want to have a new or first space shuttle launching ramp in the world.

Originality/value

Although some climatic conditions are pointed out on the location of the space shuttle launching ramp, in literature, there is not a comprehensive and detailed evaluation example as much as the model proposed in this study. Therefore, this study is the first in terms of the proposed model and applied techniques in the sectoral sense. In addition, the study is also a guide for solving the original model which is revealed in the selection of the most suitable alternative city for space shuttle launching ramp by different multi-criteria decision-making methods.
De-commemoration of an urban street in Egypt: the case of Gameat-Aldowel-Alarabyia street
Authors: Abdelwahab Mona A.
Published: June 2019

Purpose

The purpose of this paper is to explore the “event” of the construction of Naguib Mahfouz Square. Drawing on the memory of Gamaet-Aldowel-AlArabyia Street, it attempts to uncover the socio-cultural structures inherited in the Egyptian urban street.

Design/methodology/approach

This study adopts Foucauldian discourse on institutions of “knowledge and authority” to approach the power relations between the actors involved. This discourse was constructed through in-depth, unstructured interviews with architects and involved government personnel as well as other archival resources that included national newspapers and magazines.

Findings

This discourse reflected an institutional controversy between these actors over the perception and design of the Egyptian street, highlighting the alienation of the designer, and the user/lay-people, from the urban institution. Naguib Mahfouz Square presented a considerable deviation from the established norms of street design in Egypt at that time through its commemoration of a contemporary figure in literature, the architect’s involvement in the design process and the unfencing of urban space. This event thus questions the perception of the urban street beyond our socio-cultural inheritance, and towards street design as a performative urban act that embraces the everyday activities of lay-people in the street.

Originality/value

The paper utilises Foucauldian discourse on power to approach a case study of an urban event and space in Egypt, which has not previously been investigated thoroughly. It thus holds potential towards the resolution of inherited conflict between the urban street and the urban institution.