bluuebunny/crossref_metadata_2025_split huggingface dataset:
GI-16 lineage (624/I or Q1), there and Back Again: the history of one of the major threat for poultry farming of our era
Authors: Franzo Giovanni , Cecchinato Mattia , Tosi Giovanni , Fiorentini Laura , Faccin Francesca , Tucciarone Claudia Maria , Trogu Tiziana , Barbieri Ilaria , Massi Paola , Moreno Ana 
Published: August 2018

AbstractThe genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy.Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.
Extracellular matrix stiffness regulates force transmission pathways in multicellular ensembles of human airway smooth muscle cells
Authors: Polio Samuel R. , Stasiak Suzanne E , Krishnan Ramaswamy , Parameswaran Harikrishnan 
Published: August 2018

AbstractFor an airway or a blood vessel to narrow, there must be a connected path that links the smooth muscle (SM) cells with each other, and transmits forces around the organ, causing it to constrict. Currently, we know very little about the mechanisms that regulate force transmission pathways in a multicellular SM ensemble. Here, we used extracellular matrix (ECM) micropatterning to study force transmission in a two-cell ensemble of SM cells. Using the two-SM cell ensemble, we demonstrate (a) that ECM stiffness acts as a switch that regulates whether SM force is transmitted through the ECM or through cell-cell connections. (b) Fluorescent imaging for adherens junctions and focal adhesions show the progressive loss of cell-cell borders and the appearance of focal adhesions with the increase in ECM stiffness (confirming our mechanical measurements). (c) At the same ECM stiffness, we show that the presence of a cell-cell border substantially decreases the overall contractility of the SM cell ensemble. Our results demonstrate that connectivity among SM cells is a critical factor to consider in the development of diseases such as asthma and hypertension.
Evolution of Bacterial Gene Transfer Agents
Authors: Redfield Rosemary J. , Soucy Shannon M. 
Published: August 2018

AbstractBacterial gene transfer agents (GTAs) are small virus-like particles that package DNA fragments and inject them into cells. They are encoded by gene clusters resembling defective prophages, with genes for capsid head and tail components. These gene clusters are usually assumed to be maintained by selection for the benefits of GTA-mediated recombination, but this has never been tested. We rigorously examined the potential benefits of GTA-mediated recombination, considering separately transmission of GTA-encoding genes and recombination of all chromosomal genes. In principle GTA genes could be directly maintained if GTA particles spread them to GTA−cells often enough to compensate for the loss of GTA-producing cells. However careful bookkeeping showed that losses inevitably exceed gains for two reasons. First, cells must lyse to release particles to the environment. Second, GTA genes are not preferentially replicated before DNA is packaged. A simulation model was then used to search for conditions where recombination of chromosomal genes makes GTA+populations fitter than GTA−populations. Although the model showed that both synergistic epistasis and some modes of regulation could generate fitness benefits large enough to overcome the cost of lysis, these benefits neither allowed GTA+cells to invade GTA−populations, nor allowed GTA+populations to resist invasion by GTA−cells. Importantly, the benefits depended on highly improbable assumptions about the efficiencies of GTA production and recombination. Thus, the selective benefits that maintain GTA gene clusters over many millions of years must arise from consequences other than transfer of GTA genes or recombination of chromosomal genes.
A quantitative and predictive model for RNA binding by human Pumilio proteins
Authors: Jarmoskaite Inga , Denny Sarah K. , Vaidyanathan Pavanapuresan P. , Becker Winston R. , Andreasson Johan O.L. , Layton Curtis J. , Kappel Kalli , Shivashankar Varun , Sreenivasan Raashi , Das Rhiju , Greenleaf William J. , Herschlag Daniel 
Published: August 2018

SummaryHigh-throughput methodologies have enabled routine generation of RNA target sets and sequence motifs for RNA-binding proteins (RBPs). Nevertheless, quantitative approaches are needed to capture the landscape of RNA/RBP interactions responsible for cellular regulation. We have used the RNA-MaP platform to directly measure equilibrium binding for thousands of designed RNAs and to construct a predictive model for RNA recognition by the human Pumilio proteins PUM1 and PUM2. Despite prior findings of linear sequence motifs, our measurements revealed widespread residue flipping and instances of positional coupling. Application of our thermodynamic model to published in vivo crosslinking data reveals quantitative agreement between predicted affinities and in vivo occupancies. Our analyses suggest a thermodynamically driven, continuous Pumilio binding landscape that is negligibly affected by RNA structure or kinetic factors, such as displacement by ribosomes. This work provides a quantitative foundation for dissecting the cellular behavior of RBPs and cellular features that impact their occupancies.
Brain connectivity dynamics: Multilayer network switching rate predicts brain performance
Authors: Pedersen Mangor , Zalesky Andrew , Omidvarnia Amir , Jackson Graeme D. 
Published: August 2018

AbstractLarge-scale brain dynamics measures repeating spatiotemporal connectivity patterns that reflect a range of putative different brain states that underlie the dynamic repertoire of brain functions. The role of transition between brain networks is poorly understood and whether switching between these states is important for behavior has been little studied. Our aim here is to model switching between functional brain networks using multilayer network methods and test for associations between model parameters and behavioral measures. We calculated time-resolved functional MRI (fMRI) connectivity from one-hour long data recordings in 1003 healthy human adults from the Human Connectome Project. The time-resolved fMRI connectivity data was used to generate a spatiotemporal multilayer modularity model enabling us to quantifynetwork switchingwhich we define as the rate at which each brain region transits between different fMRI networks. We found i) an inverse relationship between network switching and connectivity dynamics –defined as the difference in variance between time-resolved fMRI connectivity signals and phase randomized surrogates–; ii) brain connectivity was lower during intervals of network switching; iii) brain areas with frequent network switching had greater temporal complexity; iv) brain areas with high network switching were located in association cortices; and v) using cross-validated Elastic Net regression, network switching predicted inter-subject variation in working memory performance, planning/reasoning and amount of sleep. Our findings shed new light on the importance of brain dynamics predicting task performance and amount of sleep. The ability to switch between network configurations thus appears to be a fundamental feature of optimal brain function.
SIS-seq, a molecular ‘time machine’, connects single cell fate with gene programs
Authors: Tian Luyi , Schreuder Jaring , Zalcenstein Daniela , Tran Jessica , Kocovski Nikolce , Su Shian , Diakumis Peter , Bahlo Melanie , Sargeant Toby , Hodgkin Phillip D. , Ritchie Matthew E. , Naik Shalin H. 
Published: August 2018

AbstractConventional single cell RNA-seq methods are destructive, such that a given cell cannot also then be tested for fate and function, without a time machine. Here, we develop a clonal method SIS-seq, whereby single cells are allowed to divide, and progeny cells are assayed separately in SISter conditions; some for fate, others by RNA-seq. By cross-correlating progenitor gene expression with mature cell fate within a clone, and doing this for many clones, we can identify the earliest gene expression signatures of dendritic cell subset development. SIS-seq could be used to study other populations harboring clonal heterogeneity, including stem, reprogrammed and cancer cells to reveal the transcriptional origins of fate decisions.
Construction and Characterization of a Synthetic Baculovirus-inducible 39K Promoter
Authors: Dong Zhan-Qi , Hu Zhi-Gang , Li Hai-Qing , Jiang Ya-Ming , Cao Ming-Ya , Chen Peng , Lu Cheng , Pan Min-Hui 
Published: August 2018

AbstractThe low expression activity and specificity of natural promoters limit the applications of genetic engineering. To construct a highly efficient synthetic inducible promoter in the Bombyx mori (Lepidoptera), we analyzed the regulatory elements and functional regions of the B. mori nucleopolyhedrovirus (BmNPV) 39K promoter. The results of truncated mutation analysis of the 39K promoter showed that the transcriptional regulatory region spanning positions -573 to -274 and +1 to +62 is essential for virus-inducible promoter activity. Further investigation using electrophoretic mobility shift assay (EMSA) revealed that the baculovirus IE-1 protein binds to the 39K promoter at the -310 to -355 region, and transcription activates the expression of 39K promoter assay. Finally, we successfully constructed a synthetic inducible promoter that increase the virus-inducing activity of other promoters using the baculovirus-inducible transcriptional activation region that binds to specific core elements of 39K (i.e., spanning the region -310 to -355). In summary, we describes a novel, synthetic, and highly efficient biological tool, namely, a virus-inducible 39K promoter, which provides endless possibilities for future gene function research, gene therapy, and pest control in genetic engineering.
Antimicrobial Susceptibility Testing ofChlamydophila pneumoniae: Pilot Study for Alternative Methods that Address the Complex Chlamydial Life Cycle
Authors: Stewart Laura S. , Alvarez-Macias Sandra , McHenry Rendie , Chappell James D. , Stratton Charles W. 
Published: August 2018

AbstractConventional susceptibility testing ofChlamydophila pneumoniaedoes not account for the complex life cycle that takes place in an obligatory intracellular niche and involves multiple morphological forms. Some of these forms (elementary bodies and cryptic bodies) cause persistence and are not susceptible to antimicrobial agents. Therefore, we describe a pilot study for alternative methods of susceptibility testing ofC. pneumoniae. These methods include delaying the addition of antimicrobial agents to cell cultures for 48 hours to allow the development of an established chlamydial infection as well as the use of reverse transcriptase quantitative PCR [RT-qPCR] to measure messenger RNA. Using these methods, susceptibility testing of an established infection in Hep2 cells was compared with conventional susceptibility testing ofC. pneumoniae.Conventional antimicrobial susceptibility testing ofC. pneumoniaeresults in MICs and MBCs that would suggest that recommended treatment regimens of 2 to 3 weeks of antibiotics such as doxycycline, clarithromycin, levofloxacin, and rifabutin would be sufficient. However, susceptibility testing using an established chlamydial infection in HEp2 cells reveals that none of these agents are as inhibitory and/or bactericidal as indicated by conventional methods. The resultsof this pilot study suggest that further evaluation of chlamydial susceptibility testing methods using established infection in cell cultures and RT-qPCR to measure messenger RNA are needed to optimize treatment recommendations for chronicC. pneumoniaeinfections.
Acetylation of nuclear localization signal controls importin-mediated nuclear transport of Ku70
Authors: Fujimoto H , Ikuta T , Koike A , Koike M 
Published: August 2018

AbstractKu70 participates in various intra-and extra-nucleic processes. For multifunctional control, machinery that precisely regulates the intracellular localization of Ku70 is essential. Recently, it was reported that acetylation of Ku70 regulates its function. Here, we demonstrate that specific lysine residues in Ku70 that are targets of acetylation are critical for regulating nuclear transportin vivo. Ku70-GFP fusion proteins transiently expressed in cultured cells localized in the nucleus, whereas mimicking acetylation of K553 or K556 in the Ku70 nuclear localization signal (NLS) by substituting these lysine residues with glutamine markedly decreased the nuclear localization of Ku70. Moreover, the Ku70-importin interaction was suppressed in the K553Q and K556Q mutants. Theoretical estimations indicated that the binding energy between the Ku70 NLS and importin-α decreases with acetylation of lysine residues in the Ku70 NLS, similar to the case when these lysine residues are substituted with glutamine. These results suggest that acetylation of specific lysine residues in the Ku70 NLS is a key switch that controls the localization of Ku70 by modulating interactions between Ku70 and nuclear transport factors.
Identification of a genetic element required for spore killing in Neurospora
Authors: Rhoades Nicholas A. , Harvey Austin M. , Samarajeewa Dilini A. , Svedberg Jesper , Yusifov Aykhan , Abusharekh Anna , Manitchotpisit Pennapa , Brown Daren W. , Sharp Kevin J. , Rehard David G. , Peters Joshua , Ostolaza-Maldonado Xavier , Stephenson Jackson , Shiu Patrick K. T. , Johannesson Hanna , Hammond Thomas M. 
Published: August 2018

ABSTRACTMeiotic drive elements likeSpore killer-2(Sk-2) in Neurospora are transmitted through sexual reproduction to the next generation in a biased manner.Sk-2achieves this biased transmission through spore killing. Here, we identifyrfk-1as a gene required for the spore killing mechanism. Therfk-1gene is associated with a 1,481 bp DNA interval (calledAH36) near the right border of the 30 cMSk-2element, and its deletion eliminates the ability ofSk-2to kill spores. Therfk-1gene also appears to be sufficient for spore killing because its insertion into a non-Sk-2isolate disrupts sexual reproduction after the initiation of meiosis. Although the completerfk-1transcript has yet to be defined, our data indicate thatrfk-1encodes a protein of at least 39 amino acids and thatrfk-1has evolved from a partial duplication of genencu07086. We also present evidence thatrfk-1’s location near the right border ofSk-2is critical for the success of spore killing. Increasing the distance ofrfk-1from the right border ofSk-2causes it to be inactivated by a genome defense process called meiotic silencing by unpaired DNA (MSUD), adding to accumulating evidence that MSUD exists, at least in part, to protect genomes from meiotic drive.
Antimicrobial resistance prevalence, rates of hospitalization with septicemia and rates of mortality with sepsis in adults in different US states
Authors: Goldstein Edward , MacFadden Derek R. , Karaca Zeynal , Steiner Claudia A. , Viboud Cecile , Lipsitch Marc 
Published: August 2018

AbstractObjectivesRates of hospitalization with sepsis/septicemia and associated mortality in the US have risen significantly during the last two decades. Antibiotic resistance may contribute to the rates of sepsis-related outcomes through lack of clearance of bacterial infections following antibiotic treatment during different stages of infection. However, there is limited information about the relation between prevalence of resistance to various antibiotics in different bacteria and rates of sepsis-related outcomes.MethodsFor different age groups of adults (18-49y,50-64y,65-74y,75-84y,85+y) and combinations of antibiotics/bacteria, we evaluated associations between state-specific prevalence (percentage) of resistant samples for a given combination of antibiotics/bacteria among catheter-associated urinary tract infections in the CDC Antibiotic Resistance Patient Safety Atlas data between 2011-2014 and rates of hospitalization with septicemia (ICD-9 codes 038.xx present on the discharge diagnosis) reported to the Healthcare Cost and Utilization Project (HCUP), as well as rates of mortality with sepsis (ICD-10 codes A40-41.xx present on death certificate).ResultsAmong the different combinations of antibiotics/bacteria, prevalence of resistance to fluoroquinolones inE. colihad the strongest association with septicemia hospitalization rates for individuals aged over 50y, and with sepsis mortality rates for individuals aged 18-84y. A number of positive correlations between prevalence of resistance for different combinations of antibiotics/bacteria and septicemia hospitalization/sepsis mortality rates in adults were also found.ConclusionsOur findings, as well as our related work on the relation between antibiotic use and sepsis rates support the association between resistance to/use of certain antibiotics and rates of sepsis-related outcomes, suggesting the potential utility of antibiotic replacement.
Measuring interdependencies of preferred supplier enablers
Authors: C.V. Sunil Kumar , Routroy Srikanta 
Published: August 2018

PurposeThe purpose of this paper is to analyze preferred supplier enablers (PSEs) and measure the interdependencies among themselves for enhancing preferred supplier relationship.Design/methodology/approachIn the current study, an approach has been developed in which the significance of various PSEs was determined by applying Fuzzy Analytic Hierarchy Process (FAHP) and the prominent PSEs were screened out through Pareto analysis. Also, the interdependence among the prominent PSEs was measured by applying the Fuzzy Decision Making Trial and Evaluation Laboratory method in order to select the right PSEs in ascribing the Preferred Supplier Status. Finally, the weakest relationships among the PSEs were confirmed by applying the student’st-test and then an impact relationship map of PSEs was developed.FindingsThe strength of relationships among the PSEs, grouping of PSEs into causes and effects on a causal diagram and a concise impact relationship map of PSEs were determined. Further, the PSEs that a manufacturer must primarily focus and monitor were also obtained.Research limitations/implicationsThe study was conducted in an Indian electronic manufacturing environment. Therefore, the results obtained would be more relevant to the high end technology product manufacturers operating in the developing countries.Practical implicationsFrom the current study, a manufacturer can alleviate, favorably associate and integrate with the good suppliers and then eventually establish a strong supply base.Originality/valueManufacturers are looking for the closer and favored relationships by bringing in the concept of preferred supplier while dealing with their key suppliers. Thus, the results obtained from the current study would be of great assistance to a manufacturer in gaining an extra cutting-edge and, in turn, tackling the increased competitive pressures and reduced availability of resources.
On evaluation of supply chain’s ecosilient (g-resilient) performance index
Authors: Sen Dilip Kumar , Datta Saurav , Mahapatra S.S. 
Published: August 2018

PurposeRecently, in turbulent and highly competitive marketplace, organizational sustainability in the long run necessitates the adaptation of appropriate supply chain (SC) strategies. Hence, traditional SC philosophies are being restructured nowadays to fulfill different business goals. Articulation of lean, agile, green and resilient SC strategies could amply be found in the literature; however, integration of those in various modes may definitely improve overall SC’s performance. Past researchers have focused on the integration of lean, agile and green paradigms together to ensure an efficient SC construct. But the integration of green and resilient paradigm has been rarely reported in the literature. To deal with the unexpected situations/disturbances in the SC management along with embedded environmental consciousness, the purpose of this paper is to integrate the resilient SC and green SC philosophies; thereof to evaluate of an overall SC “g-resilient”/“ecosilient” index for a case automotive company.Design/methodology/approachA consolidated list consisting of supply chain practices (combining green and resilient performance indices) have been articulated in this study. A decision-making group has been assumed; where, the role of the decision makers is to provide individuals’ judgment (subjective opinion) toward determining the weight and the rating (performance extent) of various performance indices. The overall g-resilient SC performance has been determined by computing a unique ecosilient (g-resilient) index. The concepts of fuzzy performance importance index along with Degree of Similarity (DOS) adapted from fuzzy set theory (FST) have been applied to rank various performance indicators. In addition to that, the interrelationships amongst various g-resilient indices (performance indicators) have also been established through interpretive structural modeling.FindingsBy exploring the concept of fuzzy DOS, outlined in the trapezoidal fuzzy numbers set theory, various SC performance indicators have been classified into three distinct performance categories/levels (namely regretful, tolerable, and satisfactory). Such categorization has been found helpful in order to determine ill (poor) performing SC areas, which need future improvement toward boosting up the overall g-resilient index of the company’s SC.Originality/valueThe study bears significant managerial implications. The decision support framework suggested in this paper is found capable enough to determine a unique index known as “ecosilient (g-resilient) index” toward exploring “greenness” as well as “resiliency” for the case automotive company. Application potential of the proposed ecosilient (g-resilient) index evaluation system has been explored in this reporting. The recommended framework enables the managers to cope up with unexpected disruptions and found helpful in order to reduce the environmental impacts.