bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Evolution of Placental Invasion and Cancer Metastasis are Causally Linked
Authors: Kshitiz  , Afzal Junaid , Maziarz Jamie D. , Hamidzadeh Archer , Liang Cong , Erkenbrack Eric M. , Nam Hong , Haeger Jan-Dirk , Pfarrer Christiane , Hoang Thomas , Ott Troy , Spencer Thomas , Pavlicev Mihaela , Antczak Doug , Levchenko Andre , Wagner Günter P. 
Published: January 2019

AbstractAmong mammals, the extent of placental invasion is correlated with vulnerability to malignancy. Animals with more invasive placentation (e.g. humans) are more vulnerable to malignancy, whereas animals with a non-invasive placenta (e.g. ruminants) are less likely to develop malignant cancer. To explain this correlation, we propose the hypothesis ofEvolved Levels of Invasibility(ELI) positing that the permissiveness of stromal tissue to invasion is a unitary character affecting both placental and cancer invasion. We provide evidence for this hypothesis by contrasting invasion of human and bovine cancer and placental cells into a lawn of stromal cells from different species. We find that both bovine endometrial and skin fibroblasts are more resistant to invasion of placental and cancer cells than their human counterparts. Gene expression profiling identified genes with high expression in human but not bovine fibroblasts. Knocking down of a subset of them in human fibroblasts leads to significantly stronger resistance to cancer cell invasion. Comparative analysis of gene expression among mammals suggests that humans evolved higher vulnerability to malignancy than the eutherian ancestor, possibly as a correlate of more invasive placentation, and boroeutherians evolved to decrease stromal invasibility. Identifying the evolutionary determinants of stromal invasibility can provide significant insights to develop rational anti-metastatic therapeutics.
An integrated metagenome catalog reveals novel insights into the murine gut microbiome
Authors: Lesker Till Robin , Chakravarthy Abilash , Gálvez Eric. J.C. , Lagkouvardos Ilias , Baines John F. , Clavel Thomas , Sczyrba Alexander , McHardy Alice C. , Strowig Till 
Published: January 2019

AbstractThe vast complexity of host-associated microbial ecosystems requires generation of host-specific gene catalogs to survey the functions and diversity of these communities. We generated a comprehensive resource, the integrated mouse gut metagenome catalog (iMGMC), comprising 4.6 million unique genes and 660 high-quality metagenome-assembled genomes (MAGs) linked to reconstructed full-length 16S rRNA gene sequences. iMGMC enables unprecedented coverage and taxonomic resolution, i.e. more than 89% of the identified taxa are not represented in any other databases. The tool (github.com/tillrobin/iMGMC) allowed characterizing the diversity and functions of prevalent and previously unknown microbial community members along the gastrointestinal tract. Moreover, we show that integration of MAGs and 16S rRNA gene data allows a more accurate prediction of functional profiles of communities than based on 16S rRNA amplicons alone. Integrated gene catalogs such as iMGMC are needed to enhance the resolution of numerous existing and future sequencing-based studies.
A flow extension tethered particle motion assay for single-molecule proteolysis
Authors: Drabek Andrew A. , Loparo Joseph J. , Blacklow Stephen C. 
Published: January 2019

AbstractRegulated proteolysis of signaling proteins under mechanical tension enables cells to communicate with their environment in a variety of developmental and physiologic contexts. The role of force in inducing proteolytic sensitivity has been explored using magnetic tweezers at the single-molecule level with bead-tethered assays, but such efforts have been limited by challenges in ensuring that beads are not restrained by multiple tethers. Here, we describe a multiplexed assay for single-molecule proteolysis that overcomes the multiple-tether problem using a flow extension (FLEX) strategy on a microscope equipped with magnetic tweezers. Particle tracking and computational sorting of flow-induced displacements allows assignment of tethered substrates into singly-captured and multiply-tethered bins, with the fraction of fully mobile, single-tethered substrates depending inversely on the concentration of substrate loaded on the coverslip. Computational exclusion of multiply-tethered beads enables robust assessment of on-target proteolysis by the highly specific tobacco etch virus protease and the more promiscuous metalloprotease ADAM17. This method should be generally applicable to a wide range of proteases and readily extensible to robust evaluation of proteolytic sensitivity as a function of applied magnetic force.
Sex Differences in Oncogenic Mutational Processes
Authors: Li Constance H. , Prokopec Stephenie D. , Sun Ren X. , Yousif Fouad , Schmitz Nathaniel , Boutros Paul C. ,   for the PCAWG Molecular Subtypes and Clinical Correlates Working Group,   ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: January 2019

AbstractSex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here, we describe the first pan-cancer analysis of sex differences in whole genomes of 1,983 tumours of 28 subtypes from the ICGC Pan-Cancer Analysis of Whole Genomes project. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in cancer research.Sex disparities in cancer epidemiology include an increased overall cancer risk in males corresponding with higher incidence in most tumor types, even after adjusting for known risk factors1,2. Cancer mortality is also higher in males, due in part to better survival for female patients in many cancer types, including those of the colon and head & neck3. Interestingly, female colorectal cancer patients respond better to surgery4 and adjuvant chemotherapy, though this is partially due to biases in tumour location and microsatellite instability5. Similarly, premenopausal female nasopharyngeal cancer patients have improved survival regardless of tumour stage, radiation or chemotherapy regimen6. There is a growing body of evidence for sex differences in cancer genomics7-13, but their molecular origins and clinical implications remain largely elusive.Previous studies have mostly focused on protein coding regions, leaving the vast majority of the genome unexplored. We hypothesized that there are uncharacterized sex differences in the non-coding regions of the genome. Using whole genome sequencing data from the Pan-cancer Analysis of Whole Genomes (PCAWG) project14, we performed a survey of sex-biased mutations in 1,983 samples (1,213 male, 770 female) from 28 tumour subtypes, excluding those of the sex organs (Supplementary Table 1). We also excluded the X and Y chromosomes to focus on autosomal sex differences in cancers affecting both men and women, but there are known to be significant X-chromosome mutational differences between tumours arising in men and women15. Our analysis revealed sex differences in both genome-wide phenomena and in specific genes. These sex-biases occur not only at the pan-cancer level across all 1,983 samples, but also in individual tumour subtypes.
Temporal inhibition of autophagy reveals segmental reversal of aging with increased cancer risk
Authors: Cassidy Liam D , Young Andrew RJ , Young Christopher NJ , Soilleux Elizabeth J , Fielder Edward , Weigand Bettina M , Brais Rebecca , Wiggins Kimberley A , Clarke Murray CH , Jurk Diana , Passos Joao F , Narita Masashi 
Published: January 2019

AbstractAutophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to aging. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the aging process, and whether autophagy restoration can counteract these aging effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan, however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumor formation. Thus our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumor suppressive and oncogenic, sequentially.
CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis
Authors: Zhu Qian , Liu Nan , Orkin Stuart H. , Yuan Guo-Cheng 
Published: January 2019

AbstractWe introduce CUT&RUNTools as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&RUN primary cleavage data. CUT&RUNTools extracts endonuclease cut site information from sequences of short read fragments and produces single-locus binding estimates, aggregate motif footprints, and informative visualizations to support the high-resolution mapping capability of CUT&RUN. CUT&RUNTools is available at https://bitbucket.org/qzhudfci/cutruntools/.
Microbial phenotypic heterogeneity in response to a metabolic toxin: continuous, dynamically shifting distribution of formaldehyde tolerance inMethylobacterium extorquenspopulations
Authors: Lee Jessica A. , Riazi Siavash , Nemati Shahla H. , Vasdekis Andreas E. , Ridenhour Benjamin J. , Remien Christopher H. , Marx Christopher J. 
Published: January 2019

AbstractWhile microbiologists often make the simplifying assumption that genotype determines phenotype in a given environment, it is becoming increasingly apparent that phenotypic heterogeneity (in which one genotype generates multiple phenotypes simultaneously even in a uniform environment) is common in many microbial populations. The importance of phenotypic heterogeneity has been demonstrated in a number of model systems involving binary phenotypic states (e.g., growth/non-growth); however, less is known about systems involving phenotype distributions that are continuous across an environmental gradient, and how those distributions change when the environment changes. Here, we describe a novel instance of phenotypic diversity in tolerance to a metabolic toxin within wild-type populations ofMethylobacterium extorquens, a ubiquitous phyllosphere methylotroph capable of growing on the methanol periodically released from plant leaves. The first intermediate in methanol metabolism is formaldehyde, a potent cellular toxin that is lethal in high concentrations. We have found that at moderate concentrations, formaldehyde tolerance inM. extorquensis heterogeneous, with individual cells’ minimum tolerance levels ranging between 0 mM and 8 mM. This form of heterogeneity is continuous in terms of threshold (in the range of maximum tolerances possible), yet binary in outcome (at a given formaldehyde concentration, cells either grow normally or die, with no intermediate phenotype), and it is not associated with any detectable genetic mutations. Moreover, tolerance distributions within the population are dynamic, changing over time in response to growth conditions. We characterized this phenomenon using bulk liquid culture experiments, colony growth tracking, flow cytometry, time-lapse microscopy, and genome resequencing. Finally, we used mathematical modeling to better understand the processes by which cells change phenotype, and found evidence for both stochastic, bidirectional phenotype diversification and responsive, directed phenotype shifts, depending on the growth substrate and the presence of toxin.
A pair of E3 ubiquitin ligases compete to regulate filopodial dynamics and axon guidance TRIM67 regulates filopodial stability and axon guidance
Authors: Boyer Nicholas P. , McCormick Laura E. , Urbina Fabio L. , Gupton Stephanie L. 
Published: January 2019

ABSTRACTAppropriate axon guidance is necessary to form accurate neuronal connections. Guidance cues stimulate reorganization of the cytoskeleton within the distal growth cone at the tip of the extending axon. Filopodia at the periphery of the growth cone have long been considered sensors for axon guidance cues, yet how they perceive and respond to extracellular cues remains ill-defined. Our previous work found that the filopodial actin polymerase VASP is regulated via TRIM9-dependent nondegradative ubiquitination, and that appropriate VASP ubiquitination and deubiquitination are required for axon turning in response to the guidance cue netrin-1. Here we show that the TRIM9-related protein TRIM67 antagonizes VASP ubiquitination by outcompeting the TRIM9:VASP interaction. This antagonistic role is required for netrin-1 dependent filopodial responses, axon turning and branching, and fiber tract formation. We suggest a novel model that coordinated regulation of nondegradative VASP ubiquitination by a pair of ligases is a critical element of axon guidance.
A rapid method for DNA extraction of cotton mature fiber suitable for PCR fingerprinting
Authors: Ibrahim Shafik D. , Alsamman Alsamman M. , Khalifa Kareem 
Published: January 2019

AbstractEgyptian cotton with its extra-long staple fiber is the world’s finest textile crop, but it has been in a state of rapid decline for the past 20 years. One of the main problems in Egyptian cotton production that, some manufacturers are using inferior quality cotton or other cheaper cotton to cut costs. This practice impacts not only the brand owner but also the cotton farmers and producers. The ability to differentiate between different mature or processed cottons fibers according to its varietal origin is very complicated or highly expensive. We introduce the first non commercial procedure to isolate intact genomic DNA from cotton fiber with a modified CTAB protocol. This protocol was successfully used to retrieve DNA from cotton fabric and the DNA was efficient to perform PCR procedure using DNA-barcoding and SCoT assays. Additionally, we retrieved PCR markers using CAPs assay can differentiate between Egyptian and American cotton from a fiber source.
P-glycoprotein Detoxification by the Malpighian Tubules of the Desert Locust
Authors: Rossi Marta , Battisti Davide De , Niven Jeremy E. 
Published: January 2019

ABSTRACTDetoxification is essential for allowing animals to remove toxic substances present in their diet or generated as a biproduct of their metabolism. By transporting a wide range of potentially noxious substrates, active transporters of the ABC transporter family play an important role in detoxification. One such class of transporters are the multidrug resistance P-glycoprotein transporters. Here, we investigated P-glycoprotein transport in the Malpighian tubules of the desert locust (Schistocerca gregaria), a species whose diet includes plants that contain toxic secondary metabolites. To this end, we studied transporter physiology using a modified Ramsay assay in whichex vivoMalpighian tubules are incubated in different solutions containing the P-glycoprotein substrate dye rhodamine B in combination with different concentrations of the P-glycoprotein inhibitor verapamil. Our evidence shows that: (i) the Malpighian tubules contain a P-glycoprotein; (ii) tubule surface area is positively correlated with the tubule fluid secretion rate; and (iii) as the fluid secretion rate increases so too does the net extrusion of rhodamine B. We were able to quantify precisely the relationships between the fluid secretion, surface area, and net extrusion. We interpret these results in the context of the life history and foraging ecology of desert locusts. We argue that P-glycoproteins play an important role in the detoxification by contributing to the removal of xenobiotic substances from the haemolymph, thereby enabling gregarious desert locusts to maintain toxicity through the ingestion of toxic plants without suffering the deleterious effects themselves.
Knowledge management measures: an empirical investigation of Indian cement industry
Authors: Dave Manish , Singh Kanhaiya , Kumar Arya , Kumar Sachin 
Published: January 2019

Purpose
The purpose of this paper is to develop knowledge management constructs comprising of KM processes and KM practices through marketing and sales to derive competitive advantage (CA) in the cement industry.

Design/methodology/approach
A thorough and detailed analysis of the literature was carried out to develop the measures for KM practices, KM processes and their impact on CA. A total of 65 variables affecting competitiveness in the form of questionnaire were developed. The questionnaire was administered through e-mail to 962 territory sales managers (TSM) and equivalent employed in the marketing and sales function of the cement organizations in India. A total of 121 valid and complete responses were received, representing a response rate of 12.6 percent. The factor analysis was carried out on the data collected to establish reliability and validity of the measures.

Findings
A total of seven constructs pertaining to knowledge management practices and processes and competitiveness that comprises of 65 variables have been developed. The statistical results establish that the constructs and the variables considered in the study are reliable and valid.

Research limitations/implications
The sample of respondents for developing constructs consisted of TSM and equivalent employed in the marketing and sales function of cement companies in India. Research scope can be enhanced in the future study by including middle and senior level managers in cement companies to better diagnose and understand perception of KM initiatives across different levels in the cement industry. The work can also be extended to incorporate inbound logistics and procurement that directly contributes to the overall value chain to have a holistic perspective.

Practical implications
The measures developed in this study would be effective management tools for the implementation of knowledge management initiatives in the marketing and sales function to ascertain their level of implementation and impact on the competitiveness.

Originality/value
This study is probably the first of its kind in India to provide KM measures combined for practices and processes to understand the relationship with competitiveness in cement companies pertaining to marketing and sales function. It provides valuable insights as a strategic tool for investing in KM initiatives.
Supplier selection problem in IoT solutions
Authors: Agarwal Sonal , Sharma Vidushi , Pughat Anuradha 
Published: January 2019

Purpose
The use of Internet of Things (IoT) and networks has built a potential impact on the product cost and time in a company’s manufacturing process. These IoT solutions provide end-to-end visibility and faster introduction of merchandise and supplier in the market. The main aim of this research paper is to supply products with improved quality and cheaper price, whereas the rising response and quality of the client service.

Design/methodology/approach
This paper designs and develops two cases for selecting the most efficient vendor while keeping in mind the profit and cost constraints in optimization.

Findings
Outsourcing is a vital parameter to cut back the price and maximize the profit of the manufacturer. Therefore, the integration of supply chain with IoT can provide a solution to the cost optimization and supplier/vendor selection problems in supply chain management.

Research limitations/implications
The results show that the models are quite realistic and can help the IoT-based manufacturing units to make strategic decisions regarding product manufacturing and distribution.

Practical implications
The authors can further extend the model to derive the retailer’s profit function and develop the end product cost to the consumers and hence make it a n-level multi-vendor selection model for IoT-based systems.

Originality/value
The right choice of vendor for IoT-enabled business is a crucial concern. In this paper, the authors designed and developed multi-vendor models with in-house production and outsourcing decisions to meet the demand along with the vendor selection. The variable demands and designed variable unit cost function and batch order are set to make vendor selection more realistic.
Multilateral trade liberalization and developing countries’ economic exposure to shocks
Authors: Gnangnon Sena Kimm 
Published: January 2019

PurposeThe purpose of this paper is to examine the impact of multilateral trade policy (MTP) liberalization on developing countries’ economic exposure to shocks.Design/methodology/approachThe analysis is conducted on a panel data set comprising 120 countries over the period 1996–2013 and uses the within fixed effects estimator.FindingsThe empirical results suggest that over the entire sample as well as sub-samples of least developed countries (LDCs) and non-LDCs, multilateral trade liberalization have a negative and significant impact on economic exposure to shocks. Interestingly, LDCs appear to experience the highest magnitude of the reducing impact of multilateral trade liberalization on countries’ economic exposure to shocks.Research limitations/implicationsThese findings suggest that a greater cooperation among countries in the world, including among WTO members to further liberalize trade would surely contribute to reducing developing countries’ economic exposure to shocks.Practical implicationsThe current study shows that the current backlash against trade and the consequent strong appeal for domestic trade protectionist measures would likely to undermine the likelihood of further multilateral trade liberalization. One implication of this could be a rise in countries’ economic exposure to shocks.Originality/valueTo the best of the author’s knowledge, this is first the study on this matter.