bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons Learned From the Environmental Public Health Tracking Sub-County Data Pilot Project
Authors: Werner Angela K. , Strosnider Heather , Kassinger Craig , Shin Mikyong
Published: December 2017

Objective:

Small area data are key to better understanding the complex relationships between environmental health, health outcomes, and risk factors at a local level. In 2014, the Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program (Tracking Program) conducted the Sub-County Data Pilot Project with grantees to consider integration of sub-county data into the National Environmental Public Health Tracking Network (Tracking Network).

Design:

The Tracking Program and grantees developed sub-county-level data for several data sets during this pilot project, working to standardize processes for submitting data and creating required geographies. Grantees documented challenges they encountered during the pilot project and documented decisions.

Results:

This article covers the challenges revealed during the project. It includes insights into geocoding, aggregation, population estimates, and data stability and provides recommendations for moving forward.

Conclusion:

National standards for generating, analyzing, and sharing sub-county data should be established to build a system of sub-county data that allow for comparison of outcomes, geographies, and time. Increasing the availability and accessibility of small area data will not only enhance the Tracking Network's capabilities but also contribute to an improved understanding of environmental health and informed decision making at a local level.
Evaluating the Potential Health and Revenue Outcomes of a 100% Healthy Vending Machine Nutrition Policy at a Large Agency in Los Angeles County, 2013-2015
Authors: Wickramasekaran Ranjana N. , Robles Brenda , Dewey George , Kuo Tony
Published: December 2017

Context:

Healthy vending machine policies are viewed as a promising strategy for combating the growing obesity epidemic in the United States. Few studies have evaluated the short- and intermediate-term outcomes of healthy vending policies, especially for interventions that require 100% healthy products to be stocked.

Objective:

To evaluate the potential impact of a 100% healthy vending machine nutrition policy.

Design:

The vendor's quarterly revenue, product sales records, and nutritional information data from 359 unique vending machines were used to conduct a baseline and follow-up policy analysis.

Setting:

County of Los Angeles facilities, 2013-2015.

Participants:

Vending machines in facilities located across Los Angeles County.

Intervention:

A healthy vending machine policy executed in 2013 that required 100% of all products sold in contracted machines meet specified nutrition standards.

Outcome Measures:

Policy adherence; average number of calories, sugar, and sodium in food products sold; revenue change.

Results:

Policy adherence increased for snacks and beverages sold by the vending machines by 89% and 98%, respectively. Average snack and beverage revenues decreased by 37% and 34%, respectively, during the sampled period.

Conclusions:

Although a 100% healthy vending policy represents a promising strategy for encouraging purchases of healthier foods, steps should be taken to counteract potential revenue changes when planning its implementation.
Development of a Survey to Assess Local Health Department Organizational Processes and Infrastructure for Supporting Obesity Prevention
Authors: Xiao Ting , Stamatakis Katherine A. , McVay Allese B.
Published: December 2017

Local health departments (LHDs) have an important function in controlling the growing epidemic of obesity in the United States. Data are needed to gain insight into the existence of routine functions and structures of LHDs that support and sustain obesity prevention efforts. The purpose of this study was to develop and examine the reliability of measures to assess foundational LHD organizational processes and functions specific to obesity prevention. Survey measures were developed using a stratified, random sample of US LHDs to assess supportive organizational processes and infrastructure for obesity prevention representing different domains. Data were analyzed using weighted κ and intraclass correlation coefficient for assessing test-retest reliability. Most items and summary indices in the majority of survey domains had moderate/substantial or almost perfect reliability. The overall findings support this survey instrument to be a reliable measurement tool for a large number of processes and functions that comprise obesity prevention–related capacity in LHDs.
Cost Analysis of Prevention Research Centers: Instrument Development
Authors: Rabarison Kristina M. , Marcelin Rose A. , Bish Connie L. , Chandra Gyan , Massoudi Mehran S. , Greenlund Kurt J.
Published: December 2017

The 2014-2019 Prevention Research Centers (PRC) Program Funding Opportunity Announcement stated that “all applicants will be expected to collaborate with CDC to collect data to be able to perform cost analysis.” For the first time in the 30-year history of the PRC Program, a cost indicator was included in the PRC Program Evaluation and a cost analysis (CA) instrument developed. The PRC-CA instrument systematically collects data on the cost of the PRC core research project to eventually answer the CDC PRC Program Evaluation question: “To what extent do investments in PRCs support the scalability, sustainability, and effectiveness of the outcomes resulting from community-engaged efforts to improve public health?” The objective of this article is to briefly describe the development of the PRC-CA instrument. Data obtained from the PRC-CA instrument can be used to generate cost summaries to inform decision making within the PRC Program and each individual PRC.
US State Public Health Departments Special Pathogen Planning
Authors: Herstein Jocelyn J. , Biddinger Paul D. , Gibbs Shawn G. , Le Aurora B. , Jelden Katelyn C. , Hewlett Angela L. , Lowe John J.
Published: December 2017

Context:

US state public health departments played key roles in planning for and responding to confirmed and suspected cases of Ebola virus disease (EVD) during the 2014-2016 outbreak, including designating select hospitals as high-level isolation units (HLIUs) for EVD treatment in conjunction with the Centers for Disease Control and Prevention.

Objective:

To identify existing guidelines and perspectives of state health departments pertaining to the management and transport of patients with EVD and other highly hazardous communicable diseases (HHCDs).

Design:

An electronic 8-question survey with subquestions was administered as a fillable PDF.

Setting:

The survey was distributed to publicly accessible e-mails of state health department employees.

Participants:

State epidemiologists, emergency preparedness directors, or chief medical officers from each of the 50 states and the District of Columbia were contacted; a representative from 36 states and the District of Columbia responded (73%).

Main Outcome Measures:

Descriptive statistics were used to identify the proportion of state health departments with various existing protocols.

Results:

A majority of states reported that they would prefer patients confirmed with viral hemorrhagic fevers (eg, EVD, Marburg fever) and smallpox be transported to an HLIU for treatment rather than remain at the initial hospital of diagnosis. While most (89%) states had written guidelines for the safe transportation of patients with HHCDs, only 6 (16%) had written protocols for the management of accidents or other travel disruptions that may occur during HHCD transport within the state. Twenty-two state health departments (59%) had operationally exercised transport of a patient to an HLIU.

Conclusions:

Nearly half of states in the United States lack an HLIU, yet most prefer to have patients with HHCDs treated in high-level isolation. Recent budget cuts and uncertainty of future funding threaten the abilities of health departments to devote the necessary resources and staff to prepare for and deliver the desired care to HHCD cases. The lack of HLIUs in some states may complicate transport to a geographically proximate HLIU. Moreover, limited guidance on diseases that warrant high-level isolation may cause disagreement in HHCD patient placement between health departments, diagnosing facilities, and HLIUs.
Scaling up HIV self-testing in sub-Saharan Africa: a review of technology, policy and evidence
Authors: Indravudh Pitchaya P. , Choko Augustine T. , Corbett Elizabeth L.
Published: December 2017

Purpose of review

HIV self-testing (HIVST) can provide complementary coverage to existing HIV testing services and improve knowledge of status among HIV-infected individuals. This review summarizes the current technology, policy and evidence landscape in sub-Saharan Africa and priorities within a rapidly evolving field.

Recent findings

HIVST is moving towards scaled implementation, with the release of WHO guidelines, WHO prequalification of the first HIVST product, price reductions of HIVST products and a growing product pipeline. Multicountry evidence from southern and eastern Africa confirms high feasibility, acceptability and accuracy across many delivery models and populations, with minimal harms. Evidence on the effectiveness of HIVST on increased testing coverage is strong, while evidence on demand generation for follow-on HIV prevention and treatment services and cost-effective delivery is emerging. Despite these developments, HIVST delivery remains limited outside of pilot implementation.

Important technology gaps include increasing availability of more sensitive HIVST products in low and middle-income countries. Regulatory and postmarket surveillance systems for HIVST also require further development. Randomized trials evaluating the effectiveness and cost-effectiveness under multiple distribution models, including unrestricted delivery and with a focus on linkage to HIV prevention and treatment, remain priorities. Diversification of studies from west and central Africa and around blood-based products should be addressed.
Generative adversarial networks for reconstructing natural images from brain activity
Authors: Seeliger K. , Güçlü U. , Ambrogioni L. , Güçlütürk Y. , van Gerven M. A. J.
Published: December 2017

We explore a method for reconstructing visual stimuli from brain activity. Using large databases of natural images we trained a deep convolutional generative adversarial network capable of generating gray scale photos, similar to stimUli presented during two functional magnetic resonance imaging experiments. Using a linear model we learned to predict the generative model’s latent space from measured brain activity. The objective was to create an image similar to the presented stimulus image through the previously trained generator. Using this approach we were able to reconstruct structural and some semantic features of a proportion of the natural images sets. A behavioral test showed that subjects were capable of identifying a reconstruction of the original stimuhis in 67.2% and 66.4% of the cases in a pairwise comparison for the two natural image datasets respectively. our approach does not require end-to-end training of a large generative model on limited neuroimaging data. Rapid advances in generative modeling promise further improvements in reconstruction performance.
Deep Sequencing Reveals Transient Segregation of T Cell Repertoires in Splenic T Cell Zones During an Immune Response
Authors: Textor J. , Fähnrich A. , Meinhardt M. , Tune C. , Klein S. , Pagel R. , König P. , Kalies K. , Westermann J.
Published: December 2017

Immunological differences between hosts, such as diverse T-cell receptor (TCR) repertoires, are widely credited for reducing the risk of pathogen spread and adaptation in a population. Within-host immunological diversity might likewise be important for robust pathogen control, but to what extent naïve TCR repertoires differ across different locations in the same host is unclear. T-cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity. On the other hand, rapid T cell migration is expected to dilute such diversity. Here, we combined tissue micro-dissection and deep sequencing of the TCR β chain to examine the extent to which TCR repertoires differ between TCZs in murine spleens. In the absence of antigen, we found little evidence for differences between different TCZs of the same spleen. Yet, three days after immunization with sheep red blood cells, we observed a >10-fold rise in the number of clones that appeared to localize to individual zones. Remarkably, these differences largely disappeared at 4 days after immunization, when hallmarks of an ongoing immune response were still observed. These data suggest that in the absence of antigen, any repertoire differences observed between TCZs of the same host can largely be attributed to random clone distribution. Upon antigen challenge, segregated TCR compartments appear and disappear within days. Such “transient mosaic” dynamics could be an important barrier for pathogen adaptation and spread during an immune response.
Earthquake-induced habitat migration in a riparian spawning fish: implications for conservation management
Authors: Orchard Shane , Hickford Michael J. H. , Schiel David R.
Published: December 2017

Galaxias maculatus is a riparian spawning fish that supports an important recreational fishery in New Zealand with spawning habitat requirements strongly structured by salinity gradients at rivermouths. This study reports changes to the spawning habitat following a series of large earthquakes that resulted in widespread deformation of ground surfaces in the vicinity of waterways. Assessments of habitat recovery focussed on two rivers systems, the Avon and Heathcote, with pre-disturbance data available over a 20 year period. Recovery dynamics were assessed by field survey and mapping of spawning habitat prior to and on seven occasions after the disturbance event. Riparian land-use and management patterns were mapped and analysed using overlay methods in GIS. Habitat migration of up to 2 km occurred in comparison to all previous records and several anthropogenic land uses have become threats due to changed patterns of co-occurrence. Incompatible activities now affect more than half of the spawning habitat in both rivers, particularly in areas managed for flood control purposes and recreational use. The results are an example of landscape scale responses to salinity and water level changes driven by tectonic dynamics. These dynamics are not the source of the stress per se, rather, they have increased exposure to pre-existing stressors. The case illustrates important principles for managing subtle, yet widespread, change. Adaptive conservation methods and investments in information are priorities for avoiding management failure following environmental change.
Autistic traits, but not schizotypy, predict overweighting of sensory information in Bayesian visual integration
Authors: Karvelis Povilas , Seitz Aaron R. , Lawrie Stephen M. , Seriès Peggy
Published: December 2017

Recent theories propose that schizophrenia/schizotypy and autistic spectrum disorder are related to impairments in Bayesian inference i.e. how the brain integrates sensory information (likelihoods) with prior knowledge. However existing accounts fail to clarify: i) how proposed theories differ in accounts of ASD vs. schizophrenia and ii) whether the impairments result from weaker priors or enhanced likelihoods. Here, we directly address these issues by characterizing how 91 healthy participants, scored for autistic and schizotypal traits, implicitly learned and combined priors with sensory information. This was accomplished through a visual statistical learning paradigm designed to quantitatively assess variations in individuals’ likelihoods and priors. The acquisition of the priors was found to be intact along both traits spectra. However, autistic traits were associated with more veridical perception and weaker influence of expectations. Bayesian modeling revealed that this was due not to weaker prior expectations but to more precise sensory representations.
ProGeM: A framework for the prioritisation of candidate causal genes at molecular quantitative trait loci
Authors: Stacey David , Fauman Eric B. , Ziemek Daniel , Sun Benjamin B. , Harshfield Eric L. , Wood Angela M. , Butterworth Adam S. , Suhre Karsten , Paul Dirk S.
Published: December 2017

Quantitative trait locus (QTL) mapping of molecular phenotypes such as metabolites, lipids, and proteins through genome-wide association studies (GWAS) represents a powerful means of highlighting molecular mechanisms relevant to human diseases. However, a major challenge of this approach is to identify the causal gene(s) at the observed QTLs. Here we present a framework for the “Prioritisation of candidate causal Genes at Molecular QTLs” (ProGeM), which incorporates biological domain-specific annotation data alongside genome annotation data from multiple repositories. We assessed the performance of ProGeM using a reference set of 227 previously reported and extensively curated metabolite QTLs. For 98% of these loci, the expert-curated gene was one of the candidate causal genes prioritised by ProGeM. Benchmarking analyses revealed that 69% of the causal candidates were nearest to the sentinel variant at the investigated molecular QTLs, indicating that genomic proximity is the most reliable indicator of “true positive” causal genes. In contrast, cis-gene expression QTL data led to three false positive candidate causal gene assignments for every one true positive assignment. We provide evidence that these conclusions also apply to other molecular phenotypes, suggesting that ProGeM is a powerful and versatile tool for annotating molecular QTLs. ProGeM is freely available via GitHub.
Effort distribution changes effector choice, behaviour and performance: A visuomotor tracking study using finger forces
Authors: Salam Satishchandra , Varadhan SKM
Published: December 2017

Human movement and its associated performance are bounded by a hierarchy of constraints operating over certain control variables. One such variable of both physiological and behavioural importance is the mechanical effort exerted by the participating elements. Here, we explored how motor performance is affected by the distribution of work, and consequently the effort.

Using human hand as a model, we employed a visuomotor tracking task to study the associated motor performance when mechanical effort exerted by the fingers are modulated. The subject has to trace a set of ideal paths provided on visual feedback screen to reach a target through a cursor controlled by index and little finger forces. Modulation of these forces allows us to see how the perceived effort requirement affects the tracking performance. In this task demanding two-element coordination, we represent index finger as the independent/dominant element against little finger as the dependent/subjugate counterpart. We study how increasing mechanical effort contribution from the independent element leads to changes in both behaviour and performance.

We found that despite higher mechanical requirements of employing index finger to produce larger absolute force, the movement control system continues to prefer it as against little finger which could have produced smaller absolute force. Moreover, the observation of better tracking performance under larger contributions from the independent component reflects to a plausible hierarchy of constraints employed in the motor control system that operates with more than one objective, energy minimisation per se. At least for the behaviour in study, the improved motor performance suggests that the control system prefers higher independence of the participating elements.
Spatiotemporal information is differentially conveyed by hippocampal projections to the anterior olfactory nucleus during episodic-like odour memory
Authors: Aqrabawi Afif J. , Kim Jun chul
Published: December 2017

The hippocampus is essential for representing spatiotemporal context and associating it with the sensory details of daily life to form episodic memories. However, the neural circuit underlying this process remains poorly understood. We selectively inhibited hippocampal projections to the anterior olfactory nucleus (AON) during behavioural tests of contextually-cued odour recall. We found that inhibition of intermediate HPC (iHPC)-lateral AON (lAON) pathway impaired spatial odour memory while inhibition of ventral HPC (vHPC)-medial AON (mAON) pathway disrupted both spatial and temporal odour memory. Our results indicate that the spatial and temporal information of episodic-like odour memory is conveyed by topographically distinct hippocampal-AON pathways.
Long Read Annotation (LoReAn): automated eukaryotic genome annotation based on long-read cDNA sequencing
Authors: Cook David E. , Espejo Valle-Inclan Jose , Pajoro Alije , Rovenich Hanna , Thomma Bart PHJ , Faino Luigi
Published: December 2017

Single-molecule full-length cDNA sequencing can aid genome annotation by revealing transcript structure and alternative splice-forms, yet current annotation pipelines do not incorporate such information. Here we present LoReAn (LongReadAnnotation) software, an automated annotation pipeline utilizing short- and long-read cDNA sequencing, protein evidence, andab initioprediction to generate accurate genome annotations. Based on annotations of two fungal and two plant genomes, we show that LoReAn outperforms popular annotation pipelines by integrating single-molecule cDNA sequencing data generated from either the PacBio or MinION sequencing platforms, and correctly predicting gene structure and capturing genes missed by other annotation pipelines.
Repertoire analysis of antibody CDR-H3 loops suggests affinity maturation does not typically result in rigidification
Authors: Jeliazkov Jeliazko R. , Sljoka Adnan , Kuroda Daisuke , Tsuchimura Nobuyuki , Katoh Naoki , Tsumoto Kouhei , Gray Jeffrey J.
Published: December 2017

Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibody’s antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the Complementarity Determining Region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions, and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop for thousands of recently-determined homology models of the human peripheral blood cell antibody repertoire using rigidity theory. We found no clear delineation in the flexibility of naïve and antigen-experienced antibodies. To account for possible sources of error, we additionally analyzed hundreds of human and mouse antibodies in the Protein Data Bank through both rigidity theory and B-factor analysis. By both metrics, we observed only a slight decrease in the CDR-H3 loop flexibility when comparing affinity-matured antibodies to naïve antibodies, and the decrease was not as drastic as previously reported. Further analysis, incorporating molecular dynamics (MD) simulations, revealed a spectrum of changes in flexibility. Our results suggest that rigidification may be just one of many biophysical mechanisms for increasing affinity.
Locating highly correlated sources from MEG with (recursive) (R)DS-MUSIC
Authors: Mäkelä Niko , Stenroos Matti , Sarvas Jukka , Ilmoniemi Risto J.
Published: December 2017

We introduce a source localization method of the MUltiple Signal Classification (MUSIC) family that can locate brain-signal sources robustly and reliably, irrespective of their temporal correlations. The method, double-scanning (DS) MUSIC, is based on projecting out the topographies of source candidates during topographical scanning in a way that breaks the mutual dependence of highly correlated sources, but keeps the uncorrelated sources intact. We also provide a recursive version of DS-MUSIC (RDS-MUSIC), which overcomes the peak detection problem present in the non-recursive methods. We compare DS-MUSIC and RDS-MUSIC with other localization techniques in numerous simulations with varying source configurations, correlations, and signal-to-noise ratios. DS- and RDS-MUSIC were the most robust localization methods; they had a high success rate and localization accuracy for both uncorrelated and highly correlated sources. In addition, we validated RDS-MUSIC by showing that it successfully locates bilateral synchronous activity from measured auditory-evoked MEG.
FtsW activity and lipid II synthesis are required for recruitment of MurJ to midcell during cell division inEscherichia coli
Authors: Liu Xiaolong , Meiresonne Nils Y. , Bouhss Ahmed , den Blaauwen Tanneke
Published: December 2017

Peptidoglycan (PG) is the unique cell shape-determining component of the bacterial envelope, and is a key target for antibiotics. PG synthesis requires the transmembrane movement of the precursor lipid II, and MurJ has been shown to provide this activity inE. coli.However, how MurJ functionsin vivohas not been reported. Here we show that MurJ localizes both in the lateral membrane and at midcell, and is recruited to midcell simultaneously with late-localizing divisome proteins and proteins MraY and MurG. MurJ septal localization is dependent on the presence of a complete and active divisome, lipid II synthesis and PBP3/FtsW activities. Inactivation of MurJ, either directly by mutation or through binding with MTSES, did not affect the midcell localization of MurJ. Our study visualizes MurJ localizationin vivoand reveals a possible mechanism of how MurJ functions during cell division, which gives possibilities for future investigations and further antibiotics developments.
Integrated analysis of anatomical and electrophysiological human intracranial data
Authors: Stolk Arjen , Griffin Sandon M. , van der Meij Roemer , Dewar Callum , Saez Ignacio , Lin Jack J. , Piantoni Giovanni , Schoffelen Jan-Mathijs , Knight Robert T. , Oostenveld Robert
Published: December 2017

The exquisite spatiotemporal precision of human intracranial EEG recordings (iEEG) permits characterizing neural processing with a level of detail that is inaccessible to scalp-EEG, MEG, or fMRI. However, the same qualities that make iEEG an exceptionally powerful tool also present unique challenges. Until now, the fusion of anatomical data (MRI and CT images) with the electrophysiological data and its subsequent analysis has relied on technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that addresses the complexities associated with human iEEG, providing complete transparency and flexibility in the evolution of raw data into illustrative representations. The protocol is directly integrated with an open source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and employed by a large research community. We demonstrate the protocol for an example complex iEEG data set to provide an intuitive and rapid approach to dealing with both neuroanatomical information and large electrophysiological data sets. We explain how the protocol can be largely automated, taking under an hour to complete, and readily adjusted to iEEG data sets with other characteristics.
Genome wide association analysis in a mouse advanced intercross line
Authors: Gonzales Natalia M. , Seo Jungkyun , Hernandez-Cordero Ana Isabel , Pierre Celine L. St. , Gregory Jennifer S. , Distler Margaret G. , Abney Mark , Canzar Stefan , Lionikas Arimantas , Palmer Abraham A.
Published: December 2017

The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands ofcis-andtrans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ∼200 mice. We replicate an association between locomotor activity andCsmd1, which we identified in an earlier generation of this AIL, and show thatCsmd1mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.
Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
Authors: Vivek-Ananth R.P. , Mohanraj Karthikeyan , Vandanashree Muralidharan , Jhingran Anupam , Craig James P. , Samal Areejit
Published: December 2017

Aspergillus fumigatus and multiple other Aspergillus species cause a wide range of lung infections, collectively termed aspergillosis. Aspergilli are ubiquitous in environment with healthy immune systems routinely eliminating inhaled conidia, however, Aspergilli can become an opportunistic pathogen in immune-compromised patients. The aspergillosis mortality rate and emergence of drug-resistance reveals an urgent need to identify novel targets. Secreted and cell membrane proteins play a critical role in fungal-host interactions and pathogenesis. Using a computational pipeline integrating data from high-throughput experiments and bioinformatic predictions, we have identified secreted and cell membrane proteins in ten Aspergillus species known to cause aspergillosis. Small secreted and effector-like proteins similar to agents of fungal-plant pathogenesis were also identified within each secretome. A comparison with humans revealed that at least 70% of Aspergillus secretomes has no sequence similarity with the human proteome. An analysis of antigenic qualities of Aspergillus proteins revealed that the secretome is significantly more antigenic than cell membrane proteins or the complete proteome. Finally, overlaying an expression dataset, four A. fumigatus proteins upregulated during infection and with available structures, were found to be structurally similar to known drug target proteins in other organisms, and were able to dock in silico with the respective drug.
Spatio-Temporal Pattern of Appraising Social and Emotional Relevance: Evidence from Event-Related Brain Potentials
Authors: Schacht Annekathrin , Vrtička Pascal
Published: December 2017

Social information is highly intrinsically relevant for the human species because of its direct link to guiding physiological responses and behavior. Accordingly, extant functional magnetic resonance imaging (fMRI) data suggest that social content may form a unique stimulus dimension. It remains largely unknown, however, how neural activity underlying social (versus nonsocial) information processing temporally unfolds, and how such social information appraisal may interact with the processing of other stimulus characteristics, particularly emotional meaning. Here, we presented complex visual scenes differing in both social (versus nonsocial) and emotional relevance (positive, negative, neutral) intermixed with scrambled versions of these pictures to N= 24 healthy young adults. Event-related brain potentials (ERPs) to intact pictures were examined for gaining insight to the dynamics of appraisal of both dimensions, implemented within the brain. Our main finding is an early interaction between social and emotional relevance due to enhanced amplitudes of early ERP components to emotionally positive pictures of social compared to nonsocial content, presumably reflecting rapid allocation of attention and counteracting an overall negativity bias. Importantly, our ERP data show high similarity with previously observed fMRI data using the same stimuli, and source estimations located the ERP effects in overlapping occipito-temporal brain areas. Our new data suggest that relevance detection may occur already as early as around 100 ms after stimulus onset and may combine relevance checks not only examining intrinsic pleasantness/emotional valence, but also social content as a unique, highly relevant stimulus dimension.
Increasing Cas9-mediated homology-directed repair efficiency through covalent tethering of DNA repair template
Authors: Aird Eric J. , Lovendahl Klaus N. , St. Martin Amber , Harris Reuben S. , Gordon Wendy R.
Published: December 2017

The CRISPR-Cas9 system is a powerful genome-editing tool in which a guide RNA targets Cas9 to a site in the genome where the Cas9 nuclease then induces a double stranded break (DSB)1,2. The potential of CRISPR-Cas9 to deliver precise genome editing is hindered by the low efficiency of homology-directed repair (HDR), which is required to incorporate a donor DNA template encoding desired genome edits near the DSB3,4. We present a strategy to enhance HDR efficiency by covalently tethering a single-stranded donor oligonucleotide (ssODN) to the Cas9/guide RNA ribonucleoprotein (RNP) complex via a fused HUH endonuclease5, thus spatially and temporally co-localizing the DSB machinery and donor DNA. We demonstrate up to an 8-fold enhancement of HDR using several editing assays, including repair of a frameshift and in-frame insertions of protein tags. The improved HDR efficiency is observed in multiple cell types and target loci, and is more pronounced at low RNP concentrations.
Rapid diversification ofPseudomonas aeruginosain cystic fibrosis lung-like conditions
Authors: Schick Alana , Kassen Rees
Published: December 2017

Chronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogenPseudomonas aeruginosais the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation ofP. aeruginosato the unique conditions of the CF lung environment as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification ofP. aeruginosa.The increased viscosity associated with the thick mucous layer in the CF airway had little impact on within-population diversification but did promote divergence among populations. Notably,in vitroevolution recapitulated patho-adaptive traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification ofP. aeruginosaindependent of other features of the CF lung such as an active immune system or the presence of competing microbial species. They also underscore the need to obtain diverse samples ofP. aeruginosawhen developing treatment plans. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the transition from transient to chronic infection.

Significance Statement

Chronic infection with the opportunistic pathogenPseudomonas aeruginosais the leading cause of lung transplant or death in cystic fibrosis patients.P. aeruginosadiversifies in the CF lung, although why this happens remains a mystery. We allowedP. aeruginosato evolve in the laboratory under a range of conditions approximating the CF lung. The diversity of evolved populations was highest, and most closely resembled the range of phenotypes among clinical isolates, in environments resembling the spectrum of nutritional resources available in the CF lung. Our results point to the nutritional complexity of the CF lung as a major driver of diversification and they suggest that diversity could be important in the development of chronic infections.
Increased glutaminolytic flux and activation of mitochondrial metabolism by BCL2 hyperactivity in lymphoma
Authors: Kaur Kirandeep , Singh Simar , Zecena Helma , Dejean Laurent , Filipp Fabian V.
Published: December 2017

B-cell lymphoma 2 (BCL2) is an important apoptosis regulator during developmental and pathological states, and its overexpression is a key feature of several malignancies. Genomic data from The Cancer Genome Atlas (TCGA) reveals significant somatic copy number amplification, overexpression, and/or elevated protein activity of BCL2 in 50 % of diffuse large B-cell lymphoma (DLBC) patients. While its canonical role in mitochondria-directed apoptosis is well established, the effect of BCL2 on transcriptional and metabolic networks remains elusive. Using an established lymphocytic pro-B-cell line overexpressing BCL2, we identified dysregulated transcriptional and metabolic networks by transcriptomic profiling arrays. Elevated BCL2 levels affect transcription factor complexes and mitogenic programs of NF-κB/REL, HIF1A/ARNT, AP1, E2F, and STAT factors. Using stable isotope-assisted metabolic flux measurements we quantify that elevated BCL2 expression increases carbon utilization boosting cellular proliferation. Tumorigenic overexpression of BCL2 significantly increases glycolytic flux, glutaminolysis, and anaplerotic flux into the TCA cycle. At the same time, the mitochondrial acetyl-CoA pool is separated from the glycolytic one by inactivating the pyruvate dehydrogenase complex via transcriptional regulation of pyruvate dehydrogenase kinase (PDK3). As compensatory fuel, mitochondrial TCA cycle metabolism is supported by asparagine synthase (ASNS) and oxidative glutaminolysis creating targets for small molecule inhibition of glutaminase. Lymphoma cells overexpressing BCL2 contained more mitochondrial mass and were more sensitive to L-glutamine deprivation and glutaminase inhibition. Cells overexpressing a mutant BCL2 G145E, which is incapable of binding BH domain members, failed to increase proliferation, glycolysis, or glutaminolysis. Taken together, the oncogene BCL2 has the ability to ramp up a metabolic phenotype supporting proliferation independent of its anti-apoptotic role. The cellular model of BCL2 activation supports NF-KB-positive subtypes of DLBC and identifies metabolic bottlenecks with dependency on anaplerotic flux as an actionable BCL2 effector network in cancer.
Examination of the Shared Genetic Basis of Anorexia Nervosa and Obsessive-Compulsive Disorder
Authors: Yilmaz Zeynep , Halvorsen Matthew , Bryois Julien , Yu Dongmei , Thornton Laura M. , Zerwas Stephanie , Micali Nadia , Moessner Rainald , Burton Christie L. , Zai Gwyneth , Erdman Lauren , Kas Martien J. , Arnold Paul D. , Davis Lea K. , Knowles James A. , Breen Gerome , Scharf Jeremiah M. , Nestadt Gerald , Mathews Carol A. , Bulik Cynthia M. , Mattheisen Manuel , Crowley James J.
Published: December 2017

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg= 0.49 ± 0.13,p= 9.07×10−7) and a sizable SNP heritability (SNPh2= 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN/OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.
Programmable transport of micro- and nanoparticles byParamecium caudatum
Authors: Mayne Richard , Morgan Jack , Phillips Neil , Whiting James , Adamatzky Andrew
Published: December 2017

We exploit chemo- and galvanotactic behaviour ofParamecium caudatumto design a hybrid device that allows for controlled uptake, transport and deposition of environmental micro- and nanoparticulates in an aqueous medium. Manipulation of these objects is specific, programmable and parallel. We demonstrate how device operation and output interpretation may be automated via a DIY low-cost fluorescence spectrometer, driven by a microprocessor board. The applications of the device presented range from collection and detoxification of environmental contaminants (e.g. nanoparticles), to micromixing, to natural expressions of computer logic.
Comparative Annotation Toolkit (CAT) - simultaneous clade and personal genome annotation
Authors: Fiddes Ian T. , Armstrong Joel , Diekhans Mark , Nachtweide Stefanie , Kronenberg Zev N. , Underwood Jason G. , Gordon David , Earl Dent , Keane Thomas , Eichler Evan E. , Haussler David , Stanke Mario , Paten Benedict
Published: December 2017

The recent introductions of low-cost, long-read, and read-cloud sequencing technologies coupled with intense efforts to develop efficient algorithms have made affordable, high-qualityde novosequence assembly a realistic proposition. The result is an explosion of new, ultra-contiguous genome assemblies. To compare these genomes we need robust methods for genome annotation. We describe the fully open source Comparative Annotation Toolkit (CAT), which provides a flexible way to simultaneously annotate entire clades and identify orthology relationships. We show that CAT can be used to improve annotations on the rat genome, annotate the great apes, annotate a diverse set of mammals, and annotate personal, diploid human genomes. We demonstrate the resulting discovery of novel genes, isoforms and structural variants, even in genomes as well studied as rat and the great apes, and how these annotations improve cross-species RNA expression experiments.
Defining a landscape of molecular phenotypes using a simple single sample scoring method
Authors: Foroutan Momeneh , Bhuva Dharmesh D. , Horan Kristy , Lyu Ruqian , Cursons Joseph , Davis Melissa J.
Published: December 2017

Background

Gene set scoring provides a useful approach for quantifying concordance between sample transcriptomes and selected molecular signatures. Most methods use information from all samples to score an individual sample, leading to unstable scores in small data sets and introducing biases from sample composition across a data set (e.g. varying numbers of samples for different cancer subtypes). To address these issues we have developed a truly single sample scoring method, and associated R/Bioconductor package singscore.

Results

We have developed a rank-based single sample scoring method, implemented as a Bioconductor package. We use multiple cancer data sets to compare it against widely-used scoring methods, including GSVA, z-scores, PLAGE, and ssGSEA. Our approach does not depend upon background samples and thus the scores are stable regardless of the composition and number of samples in the gene expression data set. In contrast, scores obtained by GSVA, z-score, PLAGE and ssGSEA can be unstable when less data are available (nsamples < 25). We show that the computational time for singscore is faster than current implementations of GSVA and ssGSEA, and is comparable with that of z-score and PLAGE. The singscore package also produces visualisations and interactive plots that enable exploration of molecular phenotypes.

Conclusions

The single sample scoring method described here is independent of sample composition in gene expression data and thus it provides stable scores that are less likely to be influenced by unwanted variation across samples. These scores can be used for dimensional reduction of transcriptomic data and the phenotypic landscapes obtained by scoring samples against multiple molecular signatures may provide insights for sample stratification.
HumCFS: A database of fragile sites in human chromosomes
Authors: Kumar Rajesh , Nagpal Gandharva , Kumar Vinod , Usmani Salman Sadullah , Agrawal Piyush , Raghava Gajendra P.S.
Published: December 2017

Genomic instability is the hallmark of cancer and several other pathologies, such as mental retardation; preferentially occur at specific loci in genome known as chromosomal fragile sites. HumCFS (http://webs.iiitd.edu.in/raghava/humcfs/) is a manually curated database provides comprehensive information on 118 experimentally characterized fragile sites present in human chromosomes. HumCFS comprises of 19068 entries with wide range of information such as nucleotide sequence of fragile sites, their length, coordinates on the chromosome, cytoband, their inducers and possibility of fragile site occurrence i.e. either rare or common etc. Each fragile region gene is further annotated to disease database DisGenNET, to understand its disease association. Protein coding genes are identified by annotating each fragile site to UCSC genome browser (GRCh38/hg38). To know the extent of miRNA lying in fragile site region, miRNA from miRBase has been mapped. Comprehensively, HumCFS encompasses mapping of 5010 genes with 19068 transcripts, 1104 miRNA and 3737 disease-associated genes on fragile sites. In order to facilitate users, we integrate standard web-based tools for easy data retrieval and analysis.
Characterization of siderophore producing arsenic-resistantStaphylococcus sp. strain TA6 isolated from contaminated groundwater of Jorhat, Assam and its possible role in arsenic geocycle
Authors: Das Saurav , Barooah Madhumita
Published: December 2017

The presence of arsenic in sediments, carbonaceous rocks are geogenic, while its entry into the aquifers is mediated by several factors including microorganisms. It is well known that the microorganisms play a crucial role in the biogeochemical cycle of different elements. However, the precise role of bacteria in regulating the concentration of arsenic in Brahmaputra valley has not been investigated in detail. In this paper, we report the isolation of arsenic resistant bacterium TA6 with active arsenate reduction efficiency. The isolate was able to grow in arsenate concentration (250 mM) and arsenite (30 mM). Along with resistance to inorganic arsenic, it showed cross-tolerance to other heavy metals like Hg+2, Cd+2, Co+2, Ni+2, Cr+2. The bacterium also had a high siderophore activity (78.7 ± 0.004 μmol), which is positively correlated with the resistance aptitude. The biochemical test showed the TA6, a gram-positive bacterium which can hydrolyze starch and casein, produce catalase enzyme and utilizes citrate as a metabolic trait. Molecular and chemotaxonomic identification of TA6 based on 16S rRNA and FMAE analysis showed similarity with members ofStaphylococcusgenus with significant difference in sequence similarity and fatty acid composition. Based on 16S rRNA and FAME analysis it was identified asStaphylococcus sp.TA6. Rate of biotransformation showed bacterium could reduce ~88.2% of initial 2mM As(V) into As(III). The characterization of arsenate reductase enzyme with NADPH coupled assay showed the highest activity at pH 5.5 and temperature 50°C.