bluuebunny/crossref_metadata_2025 huggingface dataset:
Considering Systemic Barriers to Treating Tobacco Use in Clinical Settings in the United States
Authors: Rojewski Alana M , Bailey Steffani R , Bernstein Steven L , Cooperman Nina A , Gritz Ellen R , Karam-Hage Maher A , Piper Megan E , Rigotti Nancy A , Warren Graham W
Published: June 2018

The Comorbidity Workgroup of the Tobacco Treatment Research Network, within the Society for Research on Nicotine and Tobacco, previously highlighted the need to provide tobacco treatment to patients diagnosed with comorbid physical and mental health conditions. Yet, systemic barriers in the United States health care system prevent many patients who present for medical treatment from getting the evidence-based tobacco treatment that they need. The identified barriers include insufficient training in the epidemiologic impact of tobacco use, related disorders, and pharmacological and behavioral treatment approaches; misunderstanding among clinicians about the effectiveness of tobacco treatment; lack of therapeutic support from clinical staff; insufficient use of health information technology to improve tobacco use identification and treatment; and limited time and reimbursement for clinicians to provide treatment. We highlight three vignettes demonstrating the complexities of practical barriers at the health care system level. We consider each of the barriers in turn and discuss evidence-based strategies that could be implemented in the clinical care of patients with comorbid conditions. In addition, in the absence of compelling data to guide implementation approaches, we offer suggestions for potential strategies and avenues for future research.

Implications: Three vignettes highlighted in this article illustrate some systemic barriers to providing tobacco treatment for patients being treated for comorbid conditions. We explore the barriers to tobacco treatment and offer suggestions for changes in training, health care systems, clinical workflow, and payment systems that could enhance the reach and the quality of tobacco treatment within the US health care system.
Association of Infectious Disease Consultation With Clinical Outcomes in Patients With Staphylococcus aureus Bacteremia at Low Risk for Endocarditis
Authors: Yousaf Anna , Baird Grayson L , Mermel Leonard
Published: June 2018

Infectious disease (ID) consultation in patients with Staphylococcus aureus bacteremia who were at low risk for endocarditis and who had no secondary site of infection was associated with a longer course of antibiotics (median duration of intravenous antimicrobial therapy of 31 days and 15 days in those with and without ID consultation, respectively; P ≤ .01), and based on Kaplan-Meier survival analysis, reduced in-hospital mortality (P = .2), and reduced 30-day mortality after discharge (P = .4). ID consultation was also associated with a higher readmission rate within 90 days of discharge: 46% and 34% with and without ID consultation, respectively (P = .2).
Responsibility, prudence and health promotion
Authors: Brown R C H , Maslen H , Savulescu J
Published: June 2018

This article considers the role of responsibility in public health promotion. Efforts to tackle non-communicable diseases which focus on changing individual behaviour and reducing risk factor exposure sometimes invoke individual responsibility for adopting healthy lifestyles. We provide a critical discussion of this tendency. First, we outline some key distinctions in the philosophical literature on responsibility, and indicate how responsibility is incorporated into health promotion policies in the UK. We argue that the use of some forms of responsibility in health promotion is inappropriate. We present an alternative approach to understanding how individuals can ‘take responsibility’ for their health, based on the concept of prudence (i.e. acting in one’s interests). In this discussion, we do not prescribe or proscribe specific health promotion policies. Rather, we encourage public health professionals to consider how underlying assumptions (in this case, relating to responsibility) can shape health promotion policy, and how alternative framings (such as a shift from encouraging individual responsibility to facilitating prudence) may justify different kinds of action, for instance, shaping environments to make healthy behaviours easier, rather than using education as a tool to encourage responsible behaviour.
Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome?
Authors: Wong Jacqueline , Saver Barry , Scanlan James M. , Gianutsos Louis Paul , Bhakta Yachana , Walsh James , Plawman Abigail , Sapienza David , Rudolf Vania
Published: June 2018

Objectives:

To measure the incidence, onset, duration, and severity of neonatal abstinence syndrome (NAS) in infants born to mothers receiving buprenorphine and to assess the association between buprenorphine dose and NAS outcomes.

Methods:

We reviewed charts of all mother–infant pairs maintained on buprenorphine who delivered in our hospital from January 1, 2000 to April 1, 2016.

Results:

In 89 infants, NAS incidence requiring morphine was 43.8%. Means for morphine-treated infants included: 55.2 hours to morphine start, 15.9 days on morphine, and 20 days hospital stay. NAS requiring morphine treatment occurred in 48.5% and 41.4% of infants of mothers receiving ≤8 mg/d buprenorphine versus >8 mg/d, respectively (P = 0.39). We found no significant associations of maternal buprenorphine dose with peak NAS score, NAS severity requiring morphine, time to morphine start, peak morphine dose, or days on morphine. Among the other factors examined, only exclusive breastfeeding was significantly associated with neonatal outcomes, specifically lower odds of morphine treatment (odds ratio 0.24, P = 0.003).

Conclusions:

These findings suggest higher buprenorphine doses can be prescribed to pregnant women receiving medication therapy for addiction without increasing NAS severity. Our finding of reduced risk of NAS requiring morphine treatment also suggests breastfeeding is both safe and beneficial for these infants and should be encouraged.
Surgical Treatment of Diplopia in Graves Orbitopathy Patients
Authors: Eckstein Anja , Esser Joachim , Oeverhaus Michael , Saeed Peerooz , Jellema Hinke Marijke
Published: June 2018

Purpose:

To review the authors’ current understanding of motility dysfunction in patients with thyroid eye disease and to summarize appropriate evaluation and available management options.

Methods:

Data were retrieved from a systematic search of the literature.

Results:

Diplopia is one of the most disabling symptoms for Graves orbitopathy patients. It occurs in moderate-to-severe Graves orbitopathy stages and does not respond well to available anti-inflammatory treatment. Inflammation of extraocular muscles induces relatively rapid fibrotic and degenerative changes, which lead to scarring and loss of elasticity with preserved contractility. Inferior and medial rectus muscles are most often involved, which results in horizontal or vertical misalignment or both, and sometimes cyclotorsion. Impaired motility can also be caused by entrapment after orbital decompression. The aim of surgical correction is to restore/enlarge the field of binocular single vision and alleviate abnormal head posture. The basis for successful treatment is dependent on the identification of the involved muscles combined with the correct assessment of motility, misalignment, and binocular single vision.

Conclusions:

Due to increased muscle tightness, recessions are the first choice of surgical procedures. Dosing is the most difficult part of the surgery. Several techniques are described: deviation-correction with preoperative determination of the dose, duction-correction either by active or passive intraoperative evaluation of ductions, and the application of adjustable sutures. Achievable success rates are comparable among these techniques but are dependent on the surgeon’s experience. Cyclotorsion and misalignment after decompression and combined horizontal and vertical misalignments are more challenging to correct. Those types of deviations need special solutions like surgery on the oblique muscles and the usage of implants. The field of binocular single vision is the main outcome criteria for success, and the quantification may differ for research questions, study designs, and clinical purposes.
Huge Bursitis and Bursal Synovial Osteochondromatosis Associated With Scapular Osteochondroma Mimicking a Giant Calcific Mass of the Chest Wall
Authors: Tuncer Kutsi , Izgi Emine , Cankaya Bahar , Ogul Hayri , Kantarci Mecit
Published: June 2018

Osteochondroma is the most common benign bone tumor, but it rarely arises from the scapula. Scapulothoracic bursitis is quite rare and osteochondroma is one of the unusual causes of this condition. Synovial chondromatosis may occur extremely uncommonly in this bursa. We reported an unusual case of scapulothoracic bursitis with synovial chondromatosis, which is caused by osteochondroma. To the best of our knowledge, there is no defined chondromatosis in the scapulothoracic bursa secondary to scapular osteochondroma in the literature.
Can a power law improve prediction of pain recovery trajectory?
Authors: Hartmann George C. , George Steven Z.
Published: June 2018

Introduction:

Chronic pain results from complex interactions of different body systems. Time-dependent power laws have been used in physics, biology, and social sciences to identify when predictable output arises from complex systems. Power laws have been used successfully to study nervous system processing for memory, but there has been limited application of a power law describing pain recovery.

Objective:

We investigated whether power laws can be used to characterize pain recovery trajectories.

Methods:

This review consists of empirical examples for an individual with complex regional pain syndrome and prediction of 12-month pain recovery outcomes in a cohort of patients seeking physical therapy for musculoskeletal pain. For each example, mathematical power-law models were fitted to the data.

Results:

This review demonstrated how a time-dependent power law could be used to refine outcome prediction, offer alternate ways to define chronicity, and improve methods for imputing missing data.

Conclusion:

The overall goal of this review was to introduce new conceptual direction to improve understanding of chronic pain development using mathematical approaches successful for other complex systems. Therefore, the primary conclusions are meant to be hypothesis generating only. Future research will determine whether time-dependent power laws have a meaningful role in improving strategies for predicting pain outcomes.
Inferring time-dependent migration and coalescence patterns from genetic sequence and predictor data in structured populations
Authors: Müller Nicola F. , Dudas Gytis , Stadler Tanja
Published: June 2018

Population dynamics can be inferred from genetic sequence data using phylodynamic methods. These methods typically quantify the dynamics in unstructured populations or assume the parameters describing the dynamics to be constant through time in structured populations. Inference methods allowing for structured populations and parameters to vary through time involve many parameters which have to be inferred. Each of these parameters might be however only weakly informed by data. Here we introduce an approach that uses so-called predictors, such as geographic distance between locations, within a generalized linear model to inform the population dynamic parameters, namely the time-varying migration rates and effective population sizes under the marginal approximation of the structured coalescent. By using simulations, we show that we are able to reliably infer the parameters from phylogenetic trees. We then apply this framework to a previously described Ebola virus dataset. We infer incidence to be the strongest predictor for effective population size and geographic distance the strongest predictor for migration. This allows us to show not only on simulated data, but also on real data, that we are able to identify reasonable predictors. Overall, we provide a novel method that allows to identify predictors for migration rates and effective population sizes and to use these predictors to quantify migration rates and effective population sizes. Its implementation as part of the BEAST2 software package MASCOT allows to jointly infer population dynamics within structured populations, the phylogenetic tree, and evolutionary parameters.
A pragmatic approach to produce theoretical syntheses in ecology
Authors: Travassos-Britto Bruno , Pardini Renata , El-Hani Charbel N. , Prado Paulo I.
Published: June 2018

Theoretical syntheses have the role of describing and guiding knowledge generation, and are usually done by enunciating the conceptual bases that guide research in a given field. In fields that develop axiomatically, the conceptual basis can be easily identified in the set of axioms guiding model building. However, ecology does not develop axiomatically but rather pragmatically, i.e., ecologists do not build models based on a predefined set of assumptions (axioms). They rather resort to any information that seems useful to learn about ecological phenomena. Therefore, a theoretical synthesis in ecology cannot rely on the enunciation of axioms; instead, it requires identifying what information and knowledge ecologists use (i.e., what they decide is useful to learn). Here we present an approach for producing theoretical syntheses based on the information/knowledge most frequently used to learn about the world. The approach consists of (i) defining a phenomenon of interest; (ii) defining a collective of scientists studying the phenomenon; (iii) surveying the scientific studies about the phenomenon published by this collective; (iv) identifying the most relevant publications used in these studies; (v) identifying how the studies refer to the most relevant publications; (vi) synthesizing what is being used by this collective to learn about the phenomenon. We implemented the approach in a case study on the phenomenon of ecological succession, defining the collective as the scientists currently studying succession. We identified three propositions that synthesize the views of the defined collective about succession. The theoretical synthesis revealed that there is no clear division between “classical” and “contemporary” succession models, and that neutral models are being used to explain successional patterns alongside with models based on niche assumptions.By implementing the pragmatic approach in a case study, we show that it can be successfully used to produce syntheses describing the conceptual bases of a field, which have the potential to guide knowledge generation. As such, these syntheses fulfil the roles ascribed to scientific theories in the epistemological literature.
Synthetic protein alignments by CCMgen quantify noise in residue-residue contact prediction
Authors: Vorberg Susann , Seemayer Stefan , Söding Johannes
Published: June 2018

Compensatory mutations between protein residues that are in physical contact with each other can manifest themselves as statistical couplings between the corresponding columns in a multiple sequence alignment (MSA) of the protein family. Conversely, high coupling coefficients predict residues contacts. Methods for de-novo protein structure prediction based on this approach are becoming increasingly reliable. Their main limitation is the strong systematic and statistical noise in the estimation of coupling coefficients, which has so far limited their application to very large protein families. While most research has focused on boosting contact prediction quality by adding external information, little progress has been made to improve the statistical procedure at the core. In that regard, our lack of understanding of the sources of noise poses a major obstacle. We have developed CCMgen, the first method for simulating protein evolution by providing full control over the generation of realistic synthetic MSAs with pairwise statistical couplings between residue positions. This procedure requires an exact statistical model that reliably reproduces observed alignment statistics. With CCMpredPy we also provide an implementation of persistent contrastive divergence (PCD), a precise inference technique that enables us to learn the required high-quality statistical models. We demonstrate how CCMgen can facilitate the development and testing of contact prediction methods by analysing the systematic noise contributions from phylogeny and entropy. For that purpose we propose a simple entropy correction (EC) strategy which disentangles the correction for both sources of noise. We find that entropy contributes typically roughly twice as much noise as phylogeny.
Fine Specificity Epitope Analysis by HX-MS Identifies Contact Points on Ricin Toxin Recognized by Protective Monoclonal Antibodies
Authors: Slyke Greta Van , Angalakurthi Siva Krishna , Toth Ronald T. , Vance David J , Rong Yinghui , Ehrbar Dylan , Shi Yuqi , Russell Middaugh C. , Volkin David B. , Weis David D. , Mantis Nicholas J.
Published: June 2018

Ricin is a fast-acting protein toxin classified by the Centers for Disease Control and Prevention as a biothreat agent. In this report we describe five new mouse monoclonal antibodies (mAbs) directed against an immunodominant region, so-called epitope cluster II, on the surface of ricin’s ribosome-inactivating enzymatic subunit, RTA. The five mAbs were tested alongside four previously described cluster II-specific mAbs for their capacity to passively protect mice against 10 × LD50ricin challenge by injection. Only three of the mAbs (LE4, PH12 and TB12) afforded protection over the seven-day study period. Neither binding affinity norin vitrotoxin-neutralizing activity could fully account for LE4, PH12 and TB12’s potentin vivoactivity relative to the other six mAbs. However, epitope mapping studies by hydrogen exchange-mass spectrometry (HX-MS) revealed that LE4, PH12 and TB12 shared common contact points (i.e., “strong” protection by HX-MS) on RTA that encompassed residues 154-164 and 62-69, which correspond to RTA α-helices D-E and β-strands d-e, respectively, located on the back side of RTA relative to the active site. The other six mAbs recognized overlapping epitopes on RTA but none shared the same HX-MS profile as LE4, PH12 and TB12. A high-density competition ELISA with a panel of ricin-specific single domain camelid antibodies (VHHs) indicated that even though LE4, PH12 and TB12 make contact with similar secondary motifs, they ultimately approach RTA different from angles. These results underscore how subtle differences in epitope specificity have significant impacts on the antibody functionalityin vivoand have important implications in the design of immune-based countermeasures against ricin.
Accuracy and reliability of [11C]PBR28 specific binding estimated without the use of a reference region
Authors: Plaven-Sigray Pontus , Schain Martin , Zanderigo Francesca ,   Karolinska [11C]PBR28 study group, Rabiner Ilan , Gunn Roger , Ogden Todd , Cervenka Simon
Published: June 2018

[11C]PBR28 is a positron emission tomography radioligand used to estimate the expression of 18kDa translocator protein (TSPO). TSPO is expressed on glial cells and can function as a marker for immune activation. Since TSPO is expressed throughout the brain, no true reference region exists. For this reason, an arterial input function is required for accurate quantification of [11C]PBR28 binding and the most common outcome measure is the total distribution volume (VT). Notably, VT reflects both specific binding and non-displaceable binding (VND). Therefore, estimates of specific binding, such as binding potentials (e.g., BPND) and specific distribution volume (VS) should theoretically be more sensitive to underlying differences in TSPO expression. It is unknown, however, if unbiased and accurate estimates of these measures are obtainable for [11C]PBR28.

The Simultaneous Estimation (SIME) method uses time-activity-curves from multiple brain regions with the aim to obtain a brain-wide estimate of VND, which can subsequently be used to improve the estimation of BPND and VS. In this study we evaluated the accuracy of SIME-derived VND, and the reliability of resulting estimates of specific binding for [11C]PBR28, using a combination of simulation experiments and in vivo studies in healthy humans.

The simulation experiments showed that VND values estimated using SIME were both precise and accurate. Data from a pharmacological competition challenge showed that SIME provided VND values that were on average 19% lower than those obtained using the Lassen plot, but similar to values obtained using the Likelihood-Estimation of Occupancy technique. Test-retest data showed that SIME-derived VS values exhibited good reliability and precision, while larger variability was observed in SIME-derived BPND values.

The results support the use of SIME for quantifying specific binding of [11C]PB28, and suggest that VS can be used in preference to, or as a complement to the conventional outcome measure VT. Additional studies in patient cohorts are warranted.
Maximum likelihood estimation of fitness components in experimental evolution
Authors: Liu Jingxian , Champer Jackson , Liu Chen , Chung Joan , Reeves Riona , Luthra Anisha , Lee Yoo Lim , Clark Andrew G. , Messer Philipp W.
Published: June 2018

Estimating fitness differences between allelic variants is a central goal of experimental evolution. Current methods for inferring selection from allele frequency time series typically assume that evolutionary dynamics at the locus of interest can be described by a fixed selection coefficient. However, fitness is an aggregate of several components including mating success, fecundity, and viability, and distinguishing between these components could be critical in many scenarios. Here we develop a flexible maximum likelihood framework that can disentangle different components of fitness and estimate them individually in males and females from genotype frequency data. As a proof-of-principle, we apply our method to experimentally-evolved cage populations ofDrosophila melanogaster, in which we tracked the relative frequencies of a loss-of-function and wild-type allele ofyellow. This X-linked gene produces a recessive yellow phenotype when disrupted and is involved in male courtship ability. We find that the fitness costs of the yellow phenotype take the form of substantially reduced mating preference of wild-type females for yellow males, together with a modest reduction in the viability of yellow males and females. Our framework should be generally applicable to situations where it is important to quantify fitness components of specific genetic variants, including quantitative characterization of the population dynamics of CRISPR gene drives.
Local unfolding of the HSP27 monomer regulates chaperone activity
Authors: Alderson T. Reid , Roche Julien , Gastall Heidi Y. , Pritišanac Iva , Ying Jinfa , Bax Ad , Benesch Justin L. P. , Baldwin Andrew J.
Published: June 2018

The small heat-shock protein HSP27 is a redox-sensitive molecular chaperone that is expressed throughout the human body. Here we describe redox-induced changes to the structure, dynamics, and function of HSP27 and its conserved α-crystallin domain, and provide the first structural characterization of a small heat-shock protein monomer. While HSP27 assembles into oligomers, we show that the transiently populated monomers released upon reduction are highly active chaperonesin vitro, but are kinetically unstable and susceptible to uncontrolled aggregation. By using relaxation dispersion and high-pressure nuclear magnetic resonance spectroscopy, we reveal that the pair of β-strands that mediate dimerization become partially disordered in the monomer. Strikingly, we note that numerous HSP27 mutations associated with inherited neuropathies cluster to this unstructured region. The high degree of sequence conservation in the α-crystallin domain amongst mammalian sHSPs suggests that partially unfolded monomers may be a general, functional feature of these molecular chaperones.
Probabilistic variable-length segmentation of protein sequences for discriminative motif discovery (DiMotif) and sequence embedding (ProtVecX)
Authors: Asgari Ehsaneddin , McHardy Alice , Mofrad Mohammad R.K.
Published: June 2018

In this paper, we present peptide-pair encoding (PPE), a general-purpose probabilistic segmentation of protein sequences into commonly occurring variable-length sub-sequences. The idea of PPE segmentation is inspired by the byte-pair encoding (BPE) text compression algorithm, which has recently gained popularity in subword neural machine translation. We modify this algorithm by adding a sampling framework allowing for multiple ways of segmenting a sequence. PPE segmentation steps can be learned over a large set of protein sequences (Swiss-Prot) or even a domain-specific dataset and then applied to a set of unseen sequences. This representation can be widely used as the input to any downstream machine learning tasks in protein bioinformatics. In particular, here, we introduce this representation through protein motif discovery and protein sequence embedding. (i) DiMotif: we present DiMotif as an alignment-free discriminative motif discovery method and evaluate the method for finding protein motifs in three different settings: (1) comparison of DiMotif with two existing approaches on 20 distinct motif discovery problems which are experimentally verified, (2) classification-based approach for the motifs extracted for integrins, integrin-binding proteins, and biofilm formation, and (3) in sequence pattern searching for nuclear localization signal. The DiMotif, in general, obtained high recall scores, while having a comparable F1 score with other methods in the discovery of experimentally verified motifs. Having high recall suggests that the DiMotif can be used for short-list creation for further experimental investigations on motifs. In the classification-based evaluation, the extracted motifs could reliably detect the integrins, integrin-binding, and biofilm formation-related proteins on a reserved set of sequences with high F1 scores. (ii) ProtVecX: we extend k-mer based protein vector (ProtVec) embedding to variable-length protein embedding using PPE sub-sequences. We show that the new method of embedding can marginally outperform ProtVec in enzyme prediction as well as toxin prediction tasks. In addition, we conclude that the embeddings are beneficial in protein classification tasks when they are combined with raw k-mer features.

Availability

Implementations of our method will be available under the Apache 2 licence athttp://llp.berkeley.edu/dimotifandhttp://llp.berkeley.edu/protvecx.
Researchers collaborate with same-gendered colleagues more often than expected across the life sciences
Authors: Holman Luke , Morandin Claire
Published: June 2018

Evidence suggests that women in academia are hindered by conscious and unconscious biases, and often feel excluded from formal and informal opportunities for research collaboration. In addition to ensuring fairness and helping to redress gender imbalance in the academic workforce, increasing women’s access to collaboration could help scientific progress by drawing on more of the available human capital. Here, we test whether researchers tend to collaborate with same-gendered colleagues, using more stringent methods and a larger dataset than in past work. Our results reaffirm that researchers co-publish with colleagues of the same gender more often than expected by chance, and show that this ‘gender homophily’ is slightly stronger today than it was 10 years ago. Contrary to our expectations, we found no evidence that homophily is driven mostly by senior academics, and no evidence that homophily is stronger in fields where women are in the minority. Interestingly, journals with a high impact factor for their discipline tended to have comparatively low homophily, as predicted if mixed-gender teams produce better research. We discuss some potential causes of gender homophily in science.
Common recruitment of angular gyrus in episodic autobiographical memory and bodily self-consciousness
Authors: Bréchet Lucie , Grivaz Petr , Gauthier Baptiste , Blanke Olaf
Published: June 2018

Parietal cortex and adjacent parts of the temporal cortex have recently been involved in bodily self-consciousness (BSC) and in episodic autobiographical memory (EAM). However, the neuroanatomical relationship between both fundamental aspects of self-related processing remains currently unexplored. Here we investigated whether regions in the inferior parietal lobule (IPL) that have been involved in BSC (self-location and first-person perspective) are also activate in studies investigating autobiographical memory. To examine this relation, we performed a meta-analytical study based on functional neuroimaging studies on EAM and SAM and compared them with BSC activations. We report an anatomical overlap bilaterally in the angular gyrus (AG), but not in other parietal or temporal lobe structures between BSC and EAM. Moreover, there was no overlap between BSC and SAM, suggesting that the bilateral AG is a key structure for the conscious re-experiencing of past life episodes (EAM) and the conscious on-line experience of being located and experiencing the world in first-person (BSC).
Capturing the spatiotemporal dynamics of task-initiated thoughts with combined EEG and fMRI
Authors: Bréchet Lucie , Brunet Denis , Birot Gwénaël , Gruetter Rolf , Michel Christoph M. , Jorge João
Published: June 2018

When at rest, our mind wanders from thought to thought in distinct mental states. Despite the marked importance of ongoing mental processes, it is challenging to capture and relate these states to specific cognitive contents. In this work, we employed ultra-high field functional magnetic resonance imaging (fMRI) and high-density electroencephalography (EEG) to study the ongoing thoughts of participants instructed to retrieve self-relevant past episodes for periods of 20s. These task-initiated, participant-driven activity patterns were compared to a distinct condition where participants performed serial mental arithmetic operations, thereby shifting from self-related to self-unrelated thoughts. BOLD activity mapping revealed selective activity changes in temporal, parietal and occipital areas (“posterior hot zone”), evincing their role in integrating the re-experienced past events into conscious representations during memory retrieval. Functional connectivity analysis showed that these regions were organized in two major subparts of the default mode network, previously associated to “scene-reconstruction” and “self-experience” subsystems. EEG microstate analysis allowed studying these participant-driven thoughts in the millisecond range by determining the temporal dynamics of brief periods of stable scalp potential fields. This analysis revealed selective modulation of occurrence and duration of specific microstates in both conditions. EEG source analysis revealed similar spatial distributions between the sources of these microstates and the regions identified with fMRI. These findings support growing evidence that specific fMRI networks can be captured with EEG as repeatedly occurring, integrated brief periods of synchronized neuronal activity, lasting only fractions of seconds.

Significance

We investigated the spatiotemporal dynamics of large-scale brain networks related to specific conscious thoughts. We demonstrate here that instructing participants to direct their thoughts to either episodic autobiographic memory or to mental arithmetic modulates distinct networks both in terms of highly spatially-specific BOLD signal oscillations as well as fast sub-second dynamics of EEG microstates. The combined findings from the two modalities evince a clear link between hemodynamic and electrophysiological signatures of spontaneous brain activity by the occurrence of thoughts that last for fractions of seconds, repeatedly appearing over time as integrated coherent activities of specific large-scale networks.
A matrix protein acts as a cue to preserve collective motility ofB. subtilisbiofilm cells
Authors: Steinberg Nitai , Doron Shany , Jain Rakeshkumar , Rosenberg Gili , Teeffelen Sven van , Kolodkin-Gal Ilana
Published: June 2018

Bacteria in nature are usually found in complex multicellular communities, termed biofilms. Biofilms are generally seen as sessile structures, resulting from downregulation of motility. However, during interspecies competition and predation, biofilm cells were shown to migrate towards competitor colonies. Here, we show that a specific extracellular matrix (ECM) protein, TasA, is essential for collective migration toward potential competitors and serves as a developmental cue that increases the formation of motile offspring from sessile chains. We reveal an effective strategy to maintain migration capacities in bacterial biofilms: besides providing a three-dimensional adhesive scaffold for the cells, TasA acts as a signal within the bacterial community.
Unique molecular markers for GC-D-expressing olfactory sensory neurons and chemosensory neurons of the Grueneberg ganglion
Authors: Huang Zhi , Zimmerman Arthur D. , Munger Steven D.
Published: June 2018

The main olfactory bulb (MOB) is differentiated into subregions based on their innervation by molecularly distinct chemosensory neurons. For example, olfactory sensory neurons (OSNs) that employ a cGMP-mediated transduction cascade – guanylyl-cyclase D-expressing (GC-D+) OSNs of the main olfactory epithelium (MOE) and chemosensory neurons of the Grueneberg ganglion (GGNs) – project to distinct groups of “necklace” glomeruli encircling the caudal MOB. To better understand the unique functionality and neural circuitry of the necklace glomeruli and their associated sensory neurons, we sought to identify additional molecular markers that would differentiate GC-D+ OSNs and GGNs as well as their target glomeruli. We found in mouse that GC-D+ OSNs, but not other MOE OSNs or GGNs, express the neuropeptide CART (cocaine- and amphetamine-regulated transcript). Both GC-D+ OSNs and GGNs, but not other MOE OSNs, express the Ca2+/calmodulin-dependent phosphodiesterase Pde1a, which is immunolocalized throughout the dendrites, somata and axons of these neurons. Stronger Pde1a immunolabeling in necklace glomeruli innervated by GGNs than in those innervated by GC-D+ OSNs suggests either greater Pde1a expression in individual GGNs than in GC-D+ OSNs or a difference in sensory neuron innervation density between the two types of necklace glomeruli. Together, the unique molecular signatures of GC-D+ OSNs, GGNs and their MOB targets offer important tools for understanding the processing of chemosensory information by olfactory subsystems associated with the necklace glomeruli.
ECOLOGY, NOT DISTANCE, EXPLAINS COMMUNITY COMPOSITION IN PARASITES OF SKY-ISLAND AUDUBON'S WARBLERS
Authors: Williamson Jessie L. , Wolf Cole J. , Barrow Lisa N. , Baumann Matthew J. , Galen Spencer C. , Schmitt C. Jonathan , Schmitt Donna C. , Winter Ara S. , Witt Christopher C.
Published: June 2018

Haemosporidian parasites of birds are ubiquitous in terrestrial ecosystems, but their coevolutionary dynamics remain poorly understood. If species turnover in parasites occurs at a finer scale than species turnover in hosts, widespread hosts would encounter diverse parasites and potentially diversify as a result. Previous studies have shown that some wide-ranging hosts encounter varied haemosporidian communities throughout their range, and vice-versa. However, it remains difficult to test spatial patterns of diversity in this complex multi-host multi-parasite system because it remains inadequately surveyed. We sought to understand how and why a community of avian haemosporidian parasites varies in abundance and composition across an array of eight sky islands in southwestern North America. We tested whether bird community composition, aspects of the environment, or geographic distance explain parasite species turnover in a widespread, generalist host. We sampled 178 Audubon's Warblers (Setophaga auduboni) along elevational transects in eight mountain ranges and screened them for haemosporidian mtDNA. We tested predictors of infection using generalized linear models (GLMs) and we tested predictors of bird- and parasite-community dissimilarity using generalized dissimilarity modeling (GDM). Predictors of infection differed by genus: Parahaemoproteus was predicted by elevation and climate, Leucocytozoon varied idiosyncratically among mountain ranges, and Plasmodium was unpredictable, but rare. Parasite species turnover was nearly three-fold higher than bird species turnover and was predicted by elevation, climate, and bird community composition, but not by geographic distance. Haemosporidian communities vary strikingly at spatial scales of hundreds of kilometers, across which the bird community varies only subtly. The finer spatial scale of turnover among parasites species implies that their ranges tend to be smaller than those of their hosts. Avian host species should encounter different parasite species in different parts of their ranges, resulting in spatially varying selection on host immune systems. Furthermore, the fact that parasite turnover was predicted by bird turnover implies that different species within a host community affect each other's parasites, potentially facilitating indirect antagonistic effects.
Computer Simulations of the Humoral Immune System Reveal How Imprinting Can Affect Responses to Influenza HA Stalk with Implications for the Design of Universal Vaccines
Authors: Anderson Christopher S. , Sangster Mark Y. , Yang Hongmei , Chaudhury Sidhartha , Topham David J.
Published: June 2018

Background

Successful vaccination against the H1N1 Influenza A virus has required the continuous development of new vaccines that are antigenically similar to currently circulating strains. Vaccine strategies that can increase the cross-reactivity of the antibody response, especially to conserved regions, are essential to creating long-lasting immunity to H1N1 viruses. How pre-existing immunity affects vaccine-induced antibody cross-reactivity is still not well understood.

Methods

An immunological shape space of antigenic sites of hemagglutinin (HA) was constructed using viral sequence data. A Gillespie Algorithm-based model of the humoral immune system was used to simulate B cell responses to A/California/07/2009 (CA09) HA antigen after prior immunization with an antigenically similar or dissimilar strain. The effect of pre-existing memory B cells and antibody on the resulting antibody responses was interrogated.

Results

We found increased levels of highly-cross-reactive antibodies after immunization with antigenically dissimilar strains. This increase was dependent on pre-existing memory B cells. Furthermore, pre-existing antibody also interfered with the cross-reactive antibody response, but this effect occurred irrespective of the priming antigen.

Conclusion

These findings suggest that vaccination by divergent strains will boost highly-cross-reactive antibodies by selectively targeting memory B cells specific to conserved antigenic sites and by reducing the negative interference caused by pre-existing antibody.
GONST2 transports GDP-Mannose for sphingolipid glycosylation in the Golgi apparatus of Arabidopsis
Authors: Jing Beibei , Ishikawa Toshiki , Soltis Nicole , Inada Noriko , Liang Yan , Murawska Gosia , Andeberhan Fekadu , Pidatala Ramana , Yu Xiaolan , Baidoo Edward , Kawai-Yamada Maki , Loque Dominique , Kliebenstein Daniel J. , Dupree Paul , Mortimer Jenny C.
Published: June 2018

The Golgi lumen is the site of many different glycosylation events, including cell wall polysaccharide biosynthesis and lipid glycosylation. Transporters are necessary for the import of the substrates required for glycosylation (nucleotide sugars) from the cytosol where they are synthesized. Plants use four GDP-linked sugars to glycosylate macromolecules: GDP-L-Fucose, GDP-D-Mannose, GDP-L-Galactose and GDP-D-Glucose. Of the predicted fifty-one members of the nucleotide sugar transporter/triose phosphate transporter family in Arabidopsis, only four appear to contain the conserved motif needed for the transport of GDP-linked sugars, GOLGI LOCALIZED NUCLEOTIDE SUGAR TRANSPORTER (GONST) 1-4. Previously, we have demonstrated that GONST1 provides GDP-D-Mannose for glycosylation of a class of sphingolipids, the glycosylinositolphosphorylceramides (GIPCs). Here, we characterize its closest homologue, GONST2, and conclude that it also specifically provides substrate for GIPC glycosylation. Expression ofGONST2driven by theGONST1promoter is able to rescue the severe growth phenotype ofgonst1. Loss of GONST2 exacerbates thegonst1constitutive hypersensitive response, as well as the reduced cell wall cellulose content. Thegonst2mutant grows normally under standard conditions, but has enhanced resistance to the powdery mildew-causing fungusGolovinomyces orontii.
Inducible gene switches with memory in human T cells for cellular immunotherapy
Authors: Chakravarti Deboki , Caraballo Leidy D , Weinberg Benjamin H. , Wong Wilson W.
Published: June 2018

Cell-based therapies that employ engineered T cells—including the expression of chimeric antigen receptors (CARs)—to target cancer cells have demonstrated promising responses in clinical trials. However, engineered T cell responses must be regulated to prevent severe side effects such as cytokine storms and off-target responses. Here we present a class of recombinase-based gene circuits that will enable inducible switching between two states of adoptive T cell therapy using an FDA-approved drug, creating a generalizable platform that can be used to control when and how strongly a gene is expressed. These circuits exhibit memory such that induced T cells will maintain any changes made even when the drug inducer is removed. This memory feature avoids prolonged drug inducer exposure, thus reducing the complexity and potential side effect associated with the drug inducer. We have utilized these circuits to control the expression of an anti-Her2-CAR, demonstrating the ability of these circuits to regulate CAR expression and T cell activity. We envision this platform can be extended to regulate other genes in T cell behavior for various adoptive T cell therapies.
Machine learning to classify animal species in camera trap images: applications in ecology
Authors: Tabak Michael A. , Norouzzadeh Mohammad S. , Wolfson David W. , Sweeney Steven J. , VerCauteren Kurt C. , Snow Nathan P. , Halseth Joseph M. , Di Salvo Paul A. , Lewis Jesse S. , White Michael D. , Teton Ben , Beasley James C. , Schlichting Peter E. , Boughton Raoul K. , Wight Bethany , Newkirk Eric S. , Ivan Jacob S. , Odell Eric A. , Brook Ryan K. , Lukacs Paul M. , Moeller Anna K. , Mandeville Elizabeth G. , Clune Jeff , Miller Ryan S.
Published: June 2018

1. Motion-activated cameras (“camera traps”) are increasingly used in ecological and management studies for remotely observing wildlife and have been regarded as among the most powerful tools for wildlife research. However, studies involving camera traps result in millions of images that need to be analyzed, typically by visually observing each image, in order to extract data that can be used in ecological analyses.

2. We trained machine learning models using convolutional neural networks with the ResNet-18 architecture and 3,367,383 images to automatically classify wildlife species from camera trap images obtained from five states across the United States. We tested our model on an independent subset of images not seen during training from the United States and on an out-of-sample (or “out-of-distribution” in the machine learning literature) dataset of ungulate images from Canada. We also tested the ability of our model to distinguish empty images from those with animals in another out-of-sample dataset from Tanzania, containing a faunal community that was novel to the model.

3. The trained model classified approximately 2,000 images per minute on a laptop computer with 16 gigabytes of RAM. The trained model achieved 98% accuracy at identifying species in the United States, the highest accuracy of such a model to date. Out-of-sample validation from Canada achieved 82% accuracy, and correctly identified 94% of images containing an animal in the dataset from Tanzania. We provide an R package (Machine Learning for Wildlife Image Classification; MLWIC) that allows the users to A) implement the trained model presented here and B) train their own model using classified images of wildlife from their studies.

4. The use of machine learning to rapidly and accurately classify wildlife in camera trap images can facilitate non-invasive sampling designs in ecological studies by reducing the burden of manually analyzing images. We present an R package making these methods accessible to ecologists. We discuss the implications of this technology for ecology and considerations that should be addressed in future implementations of these methods.
Capturing variation impact on molecular interactions: the IMEx Consortium mutations data set
Authors:   The IMEx Consortium Curators, del Toro N , Duesbury M , Koch M , Perfetto L , Shrivastava A , Ochoa D , Wagih O , Piñero J , Kotlyar M , Pastrello C , Beltrao P , Furlong LI , Jurisica I , Hermjakob H , Orchard S , Porras P
Published: June 2018

The current wealth of genomic variation data identified at the nucleotide level has provided us with the challenge of understanding by which mechanisms amino acid variation affects cellular processes. These effects may manifest as distinct phenotypic differences between individuals or result in the development of disease. Physical interactions between molecules are the linking steps underlying most, if not all, cellular processes. Understanding the effects that amino acid variation of a molecule’s sequence has on its molecular interactions is a key step towards connecting a full mechanistic characterization of nonsynonymous variation to cellular phenotype. Here we present an open access resource created by IMEx database curators over 14 years, featuring 28,000 annotations fully describing the effect of individual point sequence changes on physical protein interactions. We describe how this resource was built, the formats in which the data content is provided and offer a descriptive analysis of the data set. The data set is publicly available through the IntAct website at www.ebi.ac.uk/intact/resources/datasets#mutationDs and is being enhanced with every monthly release.