bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons Learned From an Epidemiologist-Led Countywide Community Assessment for Public Health Emergency Response (CASPER) in Oregon
Authors: Repp Kimberly K. , Hawes Eva , Rees Kathleen J. , Vorderstrasse Beth , Mohnkern Sue
Published: June 2018

Context:

Conducting a large-scale Community Assessment for Public Health Emergency Response (CASPER) in a geographically and linguistically diverse county presents significant methodological challenges that require advance planning.

Program:

The Centers for Disease Control and Prevention (CDC) has adapted methodology and provided a toolkit for a rapid needs assessment after a disaster. The assessment provides representative data of the sampling frame to help guide effective distribution of resources.

Implementation:

This article describes methodological considerations and lessons learned from a CASPER exercise conducted by Washington County Public Health in June 2016 to assess community emergency preparedness. The CDC's CASPER toolkit provides detailed guidance for exercises in urban areas where city blocks are well defined with many single family homes. Converting the exercise to include rural areas with challenging geographical terrain, including accessing homes without public roads, required considerable adjustments in planning. Adequate preparations for vulnerable populations with English linguistic barriers required additional significant resources. Lessons learned are presented from the first countywide CASPER exercise in Oregon.

Evaluation:

Approximately 61% of interviews were completed, and 85% of volunteers reported they would participate in another CASPER exercise. Results from the emergency preparedness survey will be presented elsewhere.

Discussion:

This experience indicates the most important considerations for conducting a CASPER exercise are oversampling clusters, overrecruiting volunteers, anticipating the actual cost of staff time, and ensuring timely language services are available during the event.
Developing a Regional Distributed Data Network for Surveillance of Chronic Health Conditions: The Colorado Health Observation Regional Data Service
Authors: Bacon Emily , Budney Gregory , Bondy Jessica , Kahn Michael G. , McCormick Emily V. , Steiner John F. , Tabano David , Waxmonsky Jeanette A. , Zucker Rachel , Davidson Arthur J.
Published: June 2018

Electronic health records (EHRs) provide an alternative to traditional public health surveillance surveys and administrative data for measuring the prevalence and impact of chronic health conditions in populations. As the infrastructure for secondary use of EHR data improves, many stakeholders are poised to benefit from data partnerships for regional access to information. Electronic health records can be transformed into a common data model that facilitates data sharing across multiple organizations and allows data to be used for surveillance. The Colorado Health Observation Regional Data Service, a regional distributed data network, has assembled diverse data partnerships, flexible infrastructure, and transparent governance practices to better understand the health of communities through EHR-based, public health surveillance. This article describes attributes of regional distributed data networks using EHR data and the history and design of Colorado Health Observation Regional Data Service as an emerging public health surveillance tool for chronic health conditions. Colorado Health Observation Regional Data Service and our experience may serve as a model for other regions interested in similar surveillance efforts. While benefits from EHR-based surveillance are described, a number of technology, partnership, and value proposition challenges remain.
Understanding the Collaborative Planning Process in Homeless Services: Networking, Advocacy, and Local Government Support May Reduce Service Gaps
Authors: Jarpe Meghan , Mosley Jennifer E. , Smith Bikki Tran
Published: June 2018

Objective:

The Continuum of Care (CoC) process—a nationwide system of regional collaborative planning networks addressing homelessness—is the chief administrative method utilized by the US Department of Housing and Urban Development to prevent and reduce homelessness in the United States. The objective of this study is to provide a benchmark comprehensive picture of the structure and practices of CoC networks, as well as information about which of those factors are associated with lower service gaps, a key goal of the initiative.

Design:

A national survey of the complete population of CoCs in the United States was conducted in 2014 (n = 312, 75% response rate). This survey is the first to gather information on all available CoC networks. Ordinary least squares (OLS) regression was used to determine the relationship between internal networking, advocacy frequency, government investment, and degree of service gaps for CoCs of different sizes.

Setting:

United States.

Participants:

Lead contacts for CoCs (n = 312) that responded to the 2014 survey.

Main Outcome Measure:

Severity of regional service gaps for people who are homeless.

Results:

Descriptive statistics show that CoCs vary considerably in regard to size, leadership, membership, and other organizational characteristics. Several independent variables were associated with reduced regional service gaps: networking for small CoCs (β = −.39, P < .05) and local government support for midsized CoCs (β = −.10, P < .05). For large CoCs, local government support was again significantly associated with lower service gaps, but there was also a significant interaction effect between advocacy and networking (β = .04, P < .05).

Conclusions:

To reduce service gaps and better serve the homeless, CoCs should consider taking steps to improve networking, particularly when advocacy is out of reach, and cultivate local government investment and support.
Epidemiology of a bubonic plague outbreak in Glasgow, Scotland in 1900
Authors: Dean Katharine R. , Krauer Fabienne , Schmid Boris V.
Published: June 2018

On August 3, 1900, bubonic plague (Yersinia pestis) broke out in Glasgow for the first time during the Third Pandemic. The local sanitary authorities rigorously tracked the spread of the disease and they found that nearly all of the 35 cases could be linked by contact with a previous case. Despite trapping hundreds of rats in the area, there was no evidence of a rat epizootic and the investigators speculated that the outbreak could be due to human-to-human transmission of bubonic plague. Here we use a likelihood-based method to reconstruct transmission trees for the outbreak. From the description of the outbreak and the reconstructed trees, we infer several epidemiological parameters. We found that the estimated mean serial interval was 7.4 days and the mean effective reproduction number dropped below 1 after implementation of control measures. We also found that there was a high rate of secondary transmissions within households and observations of transmissions from individuals who were not terminally septicemic. Our results provide important insights into the epidemiology of plague that are useful for modeling current and historic plague epidemics.
A Model Quantitative Assessment Tool for Nonhuman Primate Environmental Enrichment Plans
Authors: Dutton Mackenzie B. , Pierre Peter J. , Bailoo Jeremy D. , Warkins Emily , Michel George F. , Bennett Allyson J.
Published: June 2018

The housing and care of captive nonhuman primates (NHP) typically meets federal regulations and standards as well as guidelines by private accreditation organizations. There is, however, a gap between such policy, common practices, and the findings of a large empirical research literature on the effects of environmental enrichment (EE), particularly with respect to the degree to which different enrichment strategies lead to a demonstrable improvement of the animal’s psychological wellbeing. Assessment tools to guide decisions about selection and refinement of EE practices are largely missing and our companion paper offers a theoretically grounded qualitative approach to the categorization and assessment of sensory, motor, and cognitive (SMC) EE strategies. Here, we propose and illustrate a model for quantitative assessment of enrichment practices using a sample of research facility, zoo, and sanctuary NHP environmental enrichment plans (EEP). Our scoring technique provides a means for comparing the efficacy of different strategies across facilities and allows for the selection of priority areas for improvement. Overall, our assessment tool provides a framework that has several advantages. It is inherently flexible. It can be tailored to fit a range of species. It can readily be adapted to accommodate new evidence about a specific EE strategy, or new EE strategies, or both. Because a scientifically valid evidence-based framework drives priority, our method is readily adaptable to different types of facilities and is more likely to lead to longer-term benefits, both in terms of the enhancement of psychological wellbeing of captive NHP, and with respect to the judicious use of limited resources.

Acronyms

NHP

nonhuman primates

EE

environmental enrichment

EEP

environmental enrichment plans

SMC

sensory motor cognitive

SSIB

somatic self-injurious behavior

NSSIB

non-somatic self-injurious behavior

USDA

United States Department of Agriculture

AWA

Animal Welfare Act

AZA

Association of Zoos and Aquariums

GFAS

Global Federation of Animal Sanctuaries

NRC Guide

Guide for the Care and Use of Laboratory Animals
Stem-loops direct precise processing of 3′ UTR-derived small RNA MicL
Authors: Updegrove Taylor B , Kouse Andrew B , Bandyra Katarzyna J , Storz Gisela
Published: June 2018

Increasing numbers of 3′UTR-derived small, regulatory RNAs (sRNAs) are being discovered in bacteria, most generated by cleavage from longer transcripts. The enzyme required for these cleavages has been reported to be RNase E, the major endoribonuclease in enterica bacteria. Previous studies investigating RNase E have come to a range of different conclusions regarding the determinants for RNase E processing. To understand the sequence and structure determinants for the precise processing of the 3′ UTR-derived sRNAs, we examined the cleavage of multiple mutant and chimeric derivatives of the 3′ UTR-derived MicL sRNA in vivo and in vitro. Our results revealed that tandem stem-loops 3′ to the cleavage site define optimal, correctly-positioned cleavage of MicL and likely other similar sRNAs. Moreover, our assays of MicL, ArcZ and CpxQ showed that sRNAs exhibit differential sensitivity to RNase E, likely a consequence of a hierarchy of sRNA features recognized by the endonuclease.
Memory for non-painful auditory items is influenced by whether they are experienced in a context involving painful electrical stimulation
Authors: Vogt Keith M. , Norton Caroline M. , Speer Lauren E. , Tremel Joshua J. , Ibinson James W. , Reder Lynne M. , Fiez Julie A.
Published: June 2018

In this study, we sought to examine the effect of pain on memory. Subjects heard a series of words and made categorization decisions in two different contexts. One context included painful shocks administered just after presentation of some of the words; the other context involved no shocks. For the context that included painful stimulations, every other word was followed by a shock and subjects were informed to expect this pattern. Word lists were repeated three times within each context in randomized order, with different category judgments but consistent pain-word pairings. After a brief delay, recognition memory was assessed. Non-pain words from the pain context were less strongly encoded than non-pain words from the completely pain-free context. An important accompanying finding is that response times to repeated experimental items were slower for non-pain words from the pain context, compared to non-pain words from the completely pain-free context. This demonstrates that the effect of pain on memory may generalize to non-pain items experienced in the same experimental context.
Uneven distribution of cobamide biosynthesis and dependence in bacteria predicted by comparative genomics
Authors: Shelton Amanda N. , Seth Erica C. , Mok Kenny C. , Han Andrew W. , Jackson Samantha N. , Haft David R. , Taga Michiko E.
Published: June 2018

The vitamin B12family of cofactors known as cobamides are essential for a variety of microbial metabolisms. We used comparative genomics of 11,000 bacterial species to analyze the extent and distribution of cobamide production and use across bacteria. We find that 86% of bacteria in this data set have at least one of 15 cobamide-dependent enzyme families, yet only 37% are predicted to synthesize cobamidesde novo. The distribution of cobamide biosynthesis varies at the phylum level, with 57% of Actinobacteria, 45% of Proteobacteria, and 30% of Firmicutes, and less than 1% of Bacteroidetes containing the complete biosynthetic pathway. Cobamide structure could be predicted for 58% of cobamide-producing species, based on the presence of signature lower ligand biosynthesis and attachment genes. Our predictions also revealed that 17% of bacteria that have partial biosynthetic pathways, yet have the potential to salvage cobamide precursors. These include a newly defined, experimentally verified category of bacteria lacking the first step in the biosynthesis pathway. These predictions highlight the importance of cobamide and cobamide precursor crossfeeding as examples of nutritional dependencies in bacteria.
miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM
Authors: Brinkmann Kerstin , Hyland Craig , de Graaf Carolyn A , Strasser Andreas , Alexander Warren S , Herold Marco J
Published: June 2018

The micro RNA cluster miR17~92, also known as oncomiR-1, impacts diverse cellular processes, such as cell survival and proliferation. Constitutive loss of miR17~92 in mice causes severe defects in skeletal development, organ development and hematopoiesis, resulting in early post-natal lethality. The critical functions of miR17~92 in a fully developed animal have not yet been explored. Here we show that deletion of miR17~92 in adult mice had no impact on their lifespan or general well-being. However, detailed analysis of the hematopoietic system in mice, revealed a dramatic reduction in all mature hematopoietic lineages, which was due to the loss of early hematopoietic stem/progenitor cells (HSPCs). Strikingly, the concomitant loss of the pro-apoptotic BH3-only protein BIM rescued the loss of the HSPCs and all of their differentiated progeny that was caused by the deletion of miR17~92. These findings demonstrate that miR17~92 is critical for the survival of HSPCs by restraining the activity of the pro-apoptotic BH3-only protein BIM.
The non-canonical SMC protein SmcHD1 antagonises TAD formation on the inactive X chromosome
Authors: Gdula Michal R , Nesterova Tatyana B , Pintacuda Greta , Godwin Jonathan , Zhan Ye , Ozadam Hakan , McClellan Michael , Moralli Daniella , Krueger Felix , Green Catherine M , Reik Wolf , Kriaucionis Skirmantas , Heard Edith , Dekker Job , Brockdorff Neil
Published: June 2018

The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), and formation of two mega-domains. In this study we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique chromosome architecture. Specifically, allelic mapping of the transcriptome and epigenome in SmcHD1 null cells revealed the appearance of sub-megabase domains defined by gene activation, CpG hypermethylation and depletion of Polycomb-mediated H3K27me3. These domains, which correlate with sites of SmcHD1 enrichment on Xi in wild-type cells, additionally adopt features of active X chromosome higher-order chromosome architecture, including partial restoration of TAD boundaries. Xi chromosome architecture changes also occurred in an acute SmcHD1 knockout model, but in this case, independent of Xi gene de-repression. We conclude that SmcHD1 is a key factor in antagonising TAD formation on Xi.
Context-dependent spatial sorting of dispersal-related traits in the invasive starlings (Sturnus vulgaris) of South Africa and Australia
Authors: Phair David J. , Roux Johannes J. Le , Berthouly-Salazar Cecile , Visser Vernon , Jansen van Vuuren Bettine , Cardilini Adam P.A. , Hui Cang
Published: June 2018

Species undergoing range expansion frequently experience increased dispersal rates, especially among invasive alien species. Such increased dispersal rates have been attributed to ‘spatial sorting’, where traits enhancing dispersal assort towards the expanding range edge while traits enhacing competitiveness are favoured within the core range. To date no single study has compared patterns of spatial sorting across multiple continents for the same species. Here we compared patterns of spatial sorting in Sturnus vulgaris, the European starling (hereafter referred to as starlings), in its invasive ranges in South Africa and Australia. Starlings have experienced similar residence times in these two countries. Using multi-scale pattern analyses and generalized additive models, we determine whether dispersal and foraging traits (i.e. the morphological attributes of wings and bills) were sorted along the distance from introduction site. We found apparent patterns of spatial sorting in Australia, but not in South Africa. This difference may be attributed to differences in dispersal rates, clinal variation, environmental heterogeneity, and thus population demography on the two continents. Genetic data suggests that starlings in South Africa have experienced frequent long distance dispersal events, which could have diluted or overridden patterns of spatial sorting.
Mapping of TNTs using Correlative Cryo-Electron Microscopy Reveals a Novel Structure
Authors: Sartori-Rupp Anna , Cervantes Diégo Cordero , Pepe Anna , Delage Elise , Gousset Karine , Corroyer-Dulmont Simon , Schmitt Christine , Krijnse-Locker Jacomina , Zurzolo Chiara
Published: June 2018

The harmonious orchestration of intercellular communication is essential for multicellular organisms. One mechanism by which cells communicate is through long, actin-rich membranous protrusions, called tunneling nanotubes, that allow for the intercellular transport of various cargoes, including viruses, organelles, and proteins between the cytoplasm of distant cells in vitro and in vivo. Over the last decade, studies have focused on their functional role but information regarding their structure and the differences with other cellular protrusions such as filopodia, is still lacking. Here, we report the structural characterization of tunneling nanotubes using correlative light- and cryo-electron microscopy approaches. We demonstrate their structural identity compared to filopodia by showing that they are comprised of a bundle of functional individual Tunneling Nanotubes containing membrane-bound compartments and allowing organelle transfer.
Decoupling tRNA promoter and processing activities enables specific Pol-II Cas9 guide RNA expression
Authors: Knapp David JHF , Michaels Yale S , Jamilly Max , Ferry Quentin RV , Barbosa Hector , Milne Thomas A , Fulga Tudor A
Published: June 2018

Spatial/temporal control of Cas9 guide RNA expression could considerably expand the utility of CRISPR-based technologies. Current approaches based on tRNA processing offer a promising strategy but suffer from high background. Here we developed a variant screening platform to identify differential sequence determinants of human tRNA promoter and processing activities. Rational design based on the ensuing principles allowed us to engineer an improved tRNA scaffold that enabled highly specific guide RNA production from a Pol-II promoter.
Low-Cost Solution for Rodent Home-Cage Behaviour Monitoring
Authors: Singh Surjeet , Contreras Edgar Bermudez , Nazari Mojtaba , Sutherland Robert J. , Mohajerani Majid H.
Published: June 2018

In the current research on measuring complex behaviours/phenotyping in rodents, most of the experimental design requires the experimenter to remove the animal from its home-cage environment and place it in an unfamiliar apparatus (novel environment). This interaction may influence behaviour, general well-being, and the metabolism of the animal, affecting the phenotypic outcome even if the data collection method is automated. Most of the commercially available solutions for home-cage monitoring are expensive and usually lack the flexibility to be incorporated with existing home-cages. Here we present a low-cost solution for monitoring home-cage behaviour of rodents that can be easily incorporated to practically any available rodent home-cage. To demonstrate the use of our system, we reliably predict the sleep/wake state of mice in their home-cage using only video. We validate these results using hippocampal local field potential (LFP) and electromyography (EMG) data. Our approach provides a low-cost flexible methodology for high-throughput studies of sleep, circadian rhythm and rodent behaviour with minimal experimenter interference.
A novel amidase signature family amidase from the marine actinomyceteSalinispora arenicolaCNS-205
Authors: Yanling Ma , Xinfeng Zhang , Rong Zeng
Published: June 2018

We cloned a new gene from the amidase signature (AS) family, designatedam, from the marine actinomyceteSalinispora arenicolaCNS-205. As indicated by bioinformatics analysis and site-directed mutagenesis, the AM protein belonged to the AS family. AM was expressed, purified, and characterised inEscherichia coliBL21 (DE3), and the AM molecular mass was determined to be 51 kDa. The optimal temperature and pH were 40 °C and pH 8.0, respectively. AM exhibited a wide substrate spectrum and showed amidase, aryl acylamidase, and acyl transferase activities. AM had high activity towards aromatic and aliphatic amides. The AM substrate specificity for anilides was very narrow; only propanil could be used as an effective substrate. The extensive substrate range of AM indicates it may have broad potential applications in biosynthetic processes and biodegradation.
Impact of Bactrocera oleae on the fungal microbiota of ripe olive drupes
Authors: Abdelfattah Ahmed , Ruano-Rosa David , Cacciola Santa O. , Li Destri Nicosia Maria G. , Schena Leonardo
Published: June 2018

The olive fruit fly (OFF), Bactrocera oleae is the most devastating pest affecting olive fruit worldwide. Previous investigations have addressed the fungal microbiome associated with olive drupes or B. oleae, but the impact of the insect on fungal communities of olive fruit remains undescribed. In the present work, the fungal microbiome of olive drupes, infested and non-infested by the OFF, was investigated in four different localities and cultivars. Olive fruit fly infestations caused a general reduction of the fungal diversity, a higher quantity of the total DNA and an increase in taxa that remained unidentified or had unknown roles. The infestations led to imbalanced fungal communities with the growth of taxa that are usually outcompeted. While it was difficult to establish a cause-effect link between fly infestation and specific fungi, it is clear that the fly alters the natural microbial balance, especially the low abundant taxa. On the other hand, the most abundant ones, were not significantly influenced by the insect. In fact, despite the slight variation between the sampling locations, Aureobasidium, Cladosporium, and Alternaria, were the dominant genera, suggesting the existence of a typical olive fungal microbiome.
Microbial Dysbiosis and polyamine metabolism as predictive markers for early detection of pancreatic cancer
Authors: Mendez Roberto , Kesh Kousik , Arora Nivedita , Di Martino Leá , McAllister Florencia , Merchant Nipun , Banerjee Sulagna , Banerjee Santanu
Published: June 2018

Purpose

The lack of tools for early detection of pancreatic ductal adenocarcinoma (PDAC) is directly correlated to the abysmal survival rate in patients. In addition to several potential detection tools under active investigation, we tested the gut microbiome and its metabolic complement as one of the earliest detection tools that could be useful in patients at high-risk for PDAC.

Experimental Design

A combination of 16s pyrosequencing and whole-genome sequencing of gut microbiota was used in a spontaneous genetically engineered PDAC murine model (KRASG12DTP53R172HPdxCre or KPC). Metabolic reconstruction of microbiome was done using the HUmanN2 pipeline. Serum polyamine levels were measured from murine and patient samples using standard methods.

Results

Results showed a progressive Proteobacterial and Firmicutes dominance in gut microbiota in early stages of PDAC development. Upon in silico reconstruction of active metabolic pathways within the altered microbial flora, polyamine and nucleotide biosynthetic pathways were significantly elevated. These metabolic products are known to be actively assimilated by the host and eventually utilized by rapidly dividing cells for proliferation validating their importance in the context of tumorigenesis. In KPC mice, as well as PDAC patients, we show significantly elevated serum polyamine concentration. Therefore, at the early stages of tumorigenesis, the gut microbial composition changes in a way to release metabolites that foster host tumorigenesis, thereby fulfilling the ‘vicious cycle hypothesis’ of the role of the microbiome in health and disease states.

Conclusions

Our results provide a potential, precise, non-invasive tool for early detection of PDAC, which will result in improved outcomes.

Synopsis

Gut microbiota changes during early stages of pancreatic ductal adenocarcinoma (PDAC) progression and contributes towards host polyamine pool. Both changes can be used as an early predictive marker for PDAC.

Translational Relevance

Pancreatic carcinogenesis progresses through pre-cancerous PanIN lesions to invasive cancer. Even though these morphological changes are histologically distinct, imaging techniques are not able to distinguish the pre-invasive PanINs from normal pancreas, making detection of a tumor at a precancerous stage impossible. Thus, majority of cases (85–90%) present with advanced pancreatic cancer at the time of diagnosis. This contributes to the dismal survival rate in this disease. Our study of gut microbiome analysis on KPC mice during tumor progression followed by metabolic reconstruction and experimental validation in human samples indicate that gut-microbiome analysis along with an analysis of the microbial metabolites can be developed as potential biomarkers for detection of PDAC at early stages when histological changes are not yet grossly apparent.
Large-scale, quantitative protein assays on a high-throughput DNA sequencing chip
Authors: Layton Curtis J , McMahon Peter L , Greenleaf William J
Published: June 2018

High-throughput DNA sequencing techniques have enabled diverse approaches for linking DNA sequence to biochemical function. In contrast, assays of protein function have substantial limitations in terms of throughput, automation, and widespread availability. We have adapted an Illumina high-throughput sequencing chip to display an immense diversity of ribosomally-translated proteins and peptides, and then carried out fluorescence-based functional assays directly on this flow cell, demonstrating that a single, widely-available high-throughput platform can perform both sequencing-by-synthesis and protein assays. We quantified the binding of the M2 anti-FLAG antibody to a library of 1.3×104 variant FLAG peptides, exploring non-additive effects of combinations of mutations and discovering a “superFLAG” epitope variant. We also measured the enzymatic activity of 1.56×105 molecular variants of full-length of human O6-alkylguanine-DNA alkyltransferase (SNAP-tag). This comprehensive corpus of catalytic rates linked to amino acid sequence perturbations revealed amino acid interaction networks and cooperativity, linked positive cooperativity to structural proximity, and revealed ubiquitous positively-cooperative interactions with histidine residues.
KH-type splicing regulatory protein controls colorectal cancer cell growth and modulates the tumor microenvironment
Authors: Caiazza Francesco , Oficjalska Katarzyna , Tosetto Miriam , Phelan James J. , Noonan Sinéad , Martin Petra , Killick Kate , Breen Laura , O’Neill Fiona , Nolan Blathnaid , Furney Simon , Power Robert , Fennelly David , Craik Charles S. , O’Sullivan Jacintha , Sheahan Kieran , Doherty Glen A. , Ryan Elizabeth J.
Published: June 2018

KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination ofin silicoanalysis of large datasets,ex vivoanalysis of protein expression in patients, and mechanistic studies usingin vitromodels of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and we validated these findings in larger independent cohortsin silico.KHSRP expression was a prognostic indicator of worse overall survival (HR=3.74, 95% CI = 1.43-22.97, p=0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G1/S transition. Additionally, KHSRP promoted a pro-angiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.
A Visualization Tool to Evaluate Pairwise Protein Structure Alignment Algorithms
Authors: Bhattacharjee Shalini , Mukhopadhyay Asish
Published: June 2018

The alignment of two protein structures is a fundamental problem in structural bioinformatics. In this paper, we propose a novel approach to measure the effectiveness of a sample of three such algorithms, DALI, TM-align and EDAlignsse. The underlying premise of our approach is that structural proximity should translate into spatial proximity.
DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis
Authors: Finak Greg , Mayer Bryan T. , Fulp William , Obrecht Paul , Sato Alicia , Chung Eva , Holman Drienna , Gottardo Raphael
Published: June 2018

A central tenet of reproducible research is that scientific results are published along with the underlying data and software code necessary to reproduce and verify the findings. A host of tools and software have been released that facilitate such work-flows and scientific journals have increasingly demanded that code and primary data be made available with publications. There has been little practical advice on implementing reproducible research work-flows for large ‘omics’ or systems biology data sets used by teams of analysts working in collaboration. In such instances it is important to ensure all analysts use the same version of a data set for their analyses. Yet, instantiating relational databases and standard operating procedures can be unwieldy, with high “startup” costs and poor adherence to procedures when they deviate substantially from an analyst’s usual work-flow. Ideally a reproducible research work-flow should fit naturally into an individual’s existing work-flow, with minimal disruption. Here, we provide an overview of how we have leveraged popular open source tools, including Bioconductor, Rmarkdown, git version control, R, and specifically R’s package system combined with a new toolDataPackageR,to implement a lightweight reproducible research work-flow for preprocessing large data sets, suitable for sharing among small-to-medium sized teams of computational scientists. Our primary contribution is theDataPackageRtool, which decouples time-consuming data processing from data analysis while leaving a traceable record of how raw data is processed into analysis-ready data sets. The software ensures packaged data objects are properly documented and performs checksum verification of these along with basic package version management, and importantly, leaves a record of data processing code in the form of package vignettes. Our group has implemented this work-flow to manage, analyze and report on pre-clinical immunological trial data from multi-center, multi-assay studies for the past three years.
Transcriptional trajectories of human kidney disease progression
Authors: Cippà Pietro E , Sun Bo , Liu Jing , Chen Liang , Naesens Maarten , McMahon Andrew P
Published: June 2018

Our molecular understanding of clinical conditions progressing from acute organ injury to irreversible dysfunction is limited. We used renal transplantation as a model to characterize the transcriptional response along the transition from acute kidney injury to allograft fibrosis in humans. The integrated analysis of 163 transcriptomes with machine learning techniques identified shared and divergent transcriptional trajectories determining distinct clinical outcomes in a heterogeneous population. The molecular map of renal responses to injury was validated in a mouse ischemia-reperfusion injury model and highlighted early markers of disease progression. This generally applicable approach opens the way for an unbiased analysis of progressive diseases.
Kinesin-Binding Protein (KBP) buffers the activity of KIF18A and KIF15 in mitosis to ensure accurate chromosome segregation
Authors: Malaby Heidi L. H. , Dumas Megan E. , Ohi Ryoma , Stumpff Jason
Published: June 2018

Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here we demonstrate that Kinesin-Binding Protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule-binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.

Kinesin-Binding Protein (KBP) is identified as a regulator of the kinesins KIF18A and KIF15 during mitosis. KBP buffers the activity of these motors to control chromosome alignment and spindle integrity in metaphase and prevent lagging chromosomes in anaphase.
The expected time to cross extended fitness plateaus
Authors: Ghafari Mahan , Weissman Daniel
Published: June 2018

For a population to acquire a complex adaptation requiring multiple individually neutral mutations, it must cross a plateau in the fitness landscape. We consider plateaus involving three mutations, and show that large populations can cross them rapidly via lineages that acquire multiple mutations while remaining at low frequency. Plateau-crossing is fastest for very large populations. At intermediate population sizes, recombination can greatly accelerate adaptation by combining independent mutant lineages to form triple-mutants. For more frequent recombination, such that the population is kept near linkage equilibrium, we extend our analysis to find simple expressions for the expected time to cross plateaus of arbitrary width.
Protonated nucleobases are not fully ionized in their chloride salt crystals and form metastable base pairs further stabilized by the surrounding anions
Authors: Kumar Prashant , Cabaj Malgorzata Katarzyna , Pazio Aleksandra , Dominiak Paulina Maria
Published: June 2018

This paper presents experimental charge-density studies of cytosinium chloride, adeninium chloride hemihydrate and guaninium dichloride crystals based on ultra-high-resolution X-ray diffraction data and extensive theoretical calculations. The results confirm that the cohesive energies of the studied systems are dominated by contributions from intermolecular electrostatic interactions, as expected for ionic crystals. Electrostatic interaction energies (Ees) usually constitute 95% of the total interaction energy. TheEesenergies in this study were several times larger in absolute value when compared, for example, with dimers of neutral nucleobases. However, they were not as large as some theoretical calculations have predicted. This was because the molecules appeared not to be fully ionized in the studied crystals. Apart from charge transfer from chlorine to the protonated nucleobases, small but visible charge redistribution within the nucleobase cations was observed. Some dimers of singly protonated bases in the studied crystals, namely a cytosinium–cytosiniumtranssugar/sugar edge pair and an adeninium–adeniniumtransHoogsteen/Hoogsteen edge pair, exhibited attractive interactions (negative values ofEes) or unusually low repulsion despite identical molecular charges. The pairs are metastable as a result of strong hydrogen bonding between bases which overcompensates the overall cation–cation repulsion, the latter being weakened due to charge transfer and molecular charge-density polarization.
Sr2Pt8−x
As: a layered incommensurately modulated metal with saturated resistivity
Authors: Martino Edoardo , Arakcheeva Alla , Autès Gabriel , Pisoni Andrea , Bachmann Maja D. , Modic Kimberly A. , Helm Toni , Yazyev Oleg V. , Moll Philip J. W. , Forró László , Katrych Sergiy
Published: June 2018

The high-pressure synthesis and incommensurately modulated structure are reported for the new compound Sr2Pt8−x
As, with x = 0.715 (5). The structure consists of Sr2Pt3As layers alternating with Pt-only corrugated grids. Ab initio calculations predict a metallic character with a dominant role of the Pt d electrons. The electrical resistivity (ρ) and Seebeck coefficient confirm the metallic character, but surprisingly, ρ showed a near-flat temperature dependence. This observation fits the description of the Mooij correlation for electrical resistivity in disordered metals, originally developed for statistically distributed point defects. The discussed material has a long-range crystallographic order, but the high concentration of Pt vacancies, incommensurately ordered, strongly influences the electronic conduction properties. This result extends the range of validity of the Mooij correlation to long-range ordered incommensurately modulated vacancies. Motivated by the layered structure, the resistivity anisotropy was measured in a focused-ion-beam micro-fabricated well oriented single crystal. A low resistivity anisotropy indicates that the layers are electrically coupled and conduction channels along different directions are intermixed.
Structure of the flavocytochrome c sulfide dehydrogenase associated with the copper-binding protein CopC from the haloalkaliphilic sulfur-oxidizing bacterium Thioalkalivibrio paradoxusARh 1
Authors: Osipov Eugeny M. , Lilina Anastasia V. , Tsallagov Stanislav I. , Safonova Tatyana N. , Sorokin Dimitry Y. , Tikhonova Tamara V. , Popov Vladimir O.
Published: June 2018

Flavocytochrome c sulfide dehydrogenase from Thioalkalivibrio paradoxus (TpFCC) is a heterodimeric protein consisting of flavin- and monohaem c-binding subunits. TpFCC was co-purified and co-crystallized with the dimeric copper-binding protein TpCopC. The structure of the TpFCC–(TpCopC)2 complex was determined by X-ray diffraction at 2.6 Å resolution. The flavin-binding subunit of TpFCC is structurally similar to those determined previously, and the structure of the haem-binding subunit is similar to that of the N-terminal domain of dihaem FCCs. According to classification based on amino-acid sequence, TpCopC belongs to a high-affinity CopC subfamily characterized by the presence of a conserved His1-Xxx-His3 motif at the N-terminus. Apparently, a unique α-helix which is present in each monomer of TpCopC at the interface with TpFCC plays a key role in complex formation. The structure of the copper-binding site in TpCopC is similar to those in other known CopC structures. His3 is not involved in binding to the copper ion and is 6–7 Å away from this ion. Therefore, the His1-Xxx-His3 motif cannot be considered to be a key factor in the high affinity of CopC for copper(II) ions. It is suggested that the TpFCC–(TpCopC)2 heterotetramer may be a component of a large periplasmic complex that is responsible for thiocyanate metabolism.
N-(4-Chlorophenyl)-N′-{4-[(Z)-hydroxy(1-oxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenyl}urea
Authors: Çelik Ísmail , Atioğlu Zeliha , Ordu Gamze , Gezegen Hayreddin , Akkurt Mehmet
Published: June 2018

In the title compound, C23H17ClN2O3, the 2,3-dihydro-1H-indene ring system (r.m.s deviation = 0.004 Å) subtends dihedral angles of 81.12 (16) and 7.56 (14)° with the chlorophenyl and benzene rings, respectively. The molecular conformation features an intramolecular O—H...O hydrogen bond, forming an S(6) ring motif. In the crystal, molecules are linked by N—H...O hydrogen bonds generating [100] chains featuring R
1
2(6) loops. Weak aromatic π–π stacking [centroid–centroid distance = 3.656 (2) Å] is also oberved.
cis-Bromidobis(ethylene-1,2-diamine)(methylamine)cobalt(III) dibromide
Authors: Manimaran S. , Govindan E. , Manjunathan M. , Sambathkumar K. , Anbalagan K.
Published: June 2018

In the title compound, [CoBr(CH5N)(C2H8N2)2]Br2, the cobalt(III) ion has a distorted octahedral coordination environment and is ligated by four N atoms in the equatorial plane, with an additional N atom and a Br− ion occupying the axial positions. In the crystal, the complex cation and the two counter-anions are linked via N—H...Br and C—H...Br hydrogen bonds, forming a supramolecular framework.
Co-simulation framework of discrete element method and multibody dynamics models
Authors: Lommen Stef , Lodewijks Gabriel , Schott Dingena L.
Published: June 2018

Purpose

Bulk material-handling equipment development can be accelerated and is less expensive when testing of virtual prototypes can be adopted. However, often the complexity of the interaction between particulate material and handling equipment cannot be handled by a single computational solver. This paper aims to establish a framework for the development, verification and application of a co-simulation of discrete element method (DEM) and multibody dynamics (MBD).

Design/methodology/approach

The two methods have been coupled in two directions, which consists of coupling the load data on the geometry from DEM to MBD and the position data from MBD to DEM. The coupling has been validated thoroughly in several scenarios, and the stability and robustness have been investigated.

Findings

All tests clearly demonstrated that the co-simulation is successful in predicting particle–equipment interaction. Examples are provided describing the effects of a coupling that is too tight, as well as a coupling that is too loose. A guideline has been developed for achieving stable and efficient co-simulations.

Originality/value

This framework shows how to achieve realistic co-simulations of particulate material and equipment interaction of a dynamic nature.
Lean supply chain practices: an exploratory study on their relationship
Authors: Tortorella Guilherme , Giglio Ricardo , Fettermmann Diego Castro , Tlapa Diego
Published: June 2018

Purpose

The purpose of this paper is to empirically investigate the relationships among the implementation of LSC practices. Particularly, the authors examine the adoption level of 27 LSC practices, which were identified in a literature review, within 113 manufacturing companies from different sectors located in Southern Brazil.

Design/methodology/approach

Data collected were analyzed by means of multivariate techniques (partial correlation analysis) and two control variables were used: level of onshore suppliers and company’s experience on lean manufacturing implementation.

Findings

The results showed that the relationship among practices may not always be synergic, since there are pairs of practices that, when concurrently implemented they tend to conflict, hindering their benefits.

Originality/value

The use of partial correlations between pairs of LSC practices provides means to better understand specific associations, disregarding the implementation effect of the whole set of practices. The research also provides managers and practitioners arguments to better comprehend how practices interact with each other under specific contexts.
Achieving integration
Authors: Robinson Jessica L. , Manrodt Karl , Murfield Monique Lynn , Boone Christopher A. , Rutner Paige
Published: June 2018

Purpose

The purpose of this paper is to propose and test a dual pathway model whereby addressing the question, “What are the effects of supply chain orientation and organizational identification on internal integration and supplier integration?”.

Design/methodology/approach

A survey design was performed to collect data from supply chain professionals regarding their organization’s supply chain orientation (SCO), organizational identification (OI) and achieved states of both internal and supplier integration. Partial least squares-structural equation modeling was performed to test the dual mediating pathways.

Findings

The results show that internal integration partially mediates relationships between SCO and supplier integration and for OI and supplier integration. In comparing the mediating effects to test competing theories, the SCO path yields stronger complementary partial mediation. This supports the proposition that SCO and OI mutually exist within an organization and influence achieved integrative behaviors. Additionally, results suggest the behavioral spillover effect exists for an internally integrated organization that has also achieved supplier integration.

Originality/value

This research makes several contributions to extant literature, including finding that SCO contributes to levels of achieved integration. Also, this research theoretically integrates literature on the social dilemma associated with supplier integration and the behavioral spillover effect, suggesting that SCO allows for positive internal integrative behaviors to spillover to integrated suppliers. Finally, this research contributes to research on OI by finding achieved integration is an outcome, which refutes a dominate theory that explains OI facilitates negative behaviors toward external organizations.