bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissection of intestines from larval zebrafish for molecular analysis
Authors: San Bilge , Aben Marco , Flik Gert , Kamminga Leonie M. 
Published: December 2018

ABSTRACTEpigenetic data obtained from whole zebrafish embryos or larvae may mask or dilute organ-specific information. Fluorescence activated cell sorting can diverge cells from their native state, and cryosections often yield insufficient material for molecular analysis. Here, we present a reproducible method for larval intestinal isolation at 5, 7, and 9 days post-fertilization, using the intestine-specific transgenetgBAC(cldn15la:GFP). With tweezers, the intestine can be pulled out of the abdomen in one smooth motion. Upon removal of adhering tissues, intestines can be directly used for analyses. Each dissection takes 3-6 minutes per fish. We demonstrate that 10 and 25 dissected intestines yield enough material for RNA-sequencing and ChIP-sequencing, respectively. This method results in high quality, live material, suitable for many downstream applications.METHOD SUMMARYWe present a reproducible method for zebrafish larval intestinal isolation which results in high quality, live material. With tweezers, the intestine can be pulled out of the abdomen and after removal of adhering tissues, intestines can be directly used for analyses. We demonstrate that 10 and 25 dissected intestines yield enough material for RNA-sequencing and ChIP-sequencing, respectively.
Optimizing the use of the Men-ACWY conjugated vaccine to control the developing meningococcal W disease outbreak in the Netherlands, a rapid analysis
Authors: van Hoek Albert Jan , Knol Mirjam , de Melker Hester , Wallinga Jacco 
Published: December 2018

AbstractBackgroundThere is a developing outbreak of Neisseria meningitidis serotype W (MenW) in the Netherlands. In response, those aged 14 months and 14 years are vaccinated with the conjugated MenACWY vaccine. In the spring of 2018 we aimed to explore the impact of adding a one-off catch-up campaign targeting those aged 15-18 years on the transmission of MenW and the cost-effectiveness of such a campaign.MethodsWe estimated the growth rate of the MenW outbreak and quantified the impact of various targeted vaccination strategies on the reproductive number, and subsequently projected the future incidence with and without vaccination. Future cases were expressed in costs and QALYS and the incremental cost-effectiveness ratio was obtained.ResultsWe estimate a reproductive number of around 1.4 (95%CI 1.2-1.7) over the period February 2016-February 2018. Adding the catch-up campaign reduces the reproductive number five years earlier than without a catch-up campaign, to a level around 1.2. The vaccination campaign, including the catch-up, will prevent around 100 cases per year in our base case scenario. Given the projected impact and realistic assumptions on costs and QALYs, adding the catch-up can be considered cost-effective using a threshold of €20,000 per QALY.ConclusionAdding the catch-up campaign targeting those aged 15-18 brings the impact of vaccination on reducing transmission five years forward and directly prevents a high-incidence age group from carriage and disease. Such a campaign can be considered cost-effective. Our study did underpin the decision to introduce a catch-up campaign in spring 2019. Furthermore, our applied method can be of interest for anyone solving vaccine allocation questions in a developing outbreak.
Disruption of IRElα through its Kinase Domain Attenuates Multiple Myeloma
Authors: Harnoss Jonathan M , Thomas Adrien Le , Marsters Scot A , Lawrence David A , Lu Min , Chen Yung-Chia Ariel , Qing Jing , Totpal Klara , Kan David , Segal Ehud , Wallweber Heidi Ackerly , Wang Weiru , Clark Kevin , Kaufman Susan , Beresini Maureen , Sandoval Wendy , Lorenzo Maria , Wu Jiansheng , Ly Justin , Bruyn Tom De , Heidersbach Amy , Haley Benjamin , Gogineni Alvin , Weimer Robby , Lee Dong , Braun Marie-Gabrielle , Rudolph Joachim , VanWyngarden Michael J , Sherbenou Daniel W , Gomez-Bougie Patricia , Amiot Martine , Acosta-Alvear Diego , Walter Peter , Ashkenazi Avi 
Published: December 2018

AbstractMultiple myeloma (MM) arises from malignant immunoglobulin-secreting plasma cells and remains an incurable, often lethal disease despite recent therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may coopt the IRE1α-XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Here we show that genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice, and augmented efficacy of two well-established frontline antimyeloma agents, bortezomib or lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the ER-associated degradation machinery, as well as cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138− cells from bone marrow of newly diagnosed MM patients or patients whose disease relapsed after 1 - 4 lines of treatment in both US- and EU-based cohorts. IRE1α inhibition preserved survival and glucose-induced insulin secretion by pancreatic microislets. Together, these results establish a strong therapeutic rationale for targeting IRE1α with kinase-based small-molecule inhibitors in MM.Significance statementMultiple myeloma (MM) is a lethal malignancy of plasma cells. MM cells have an expanded endoplasmic reticulum (ER) that is constantly under stress due to immunoglobulin hyperproduction. The ER-resident sensor IRE1α mitigates ER stress by expanding the ER’s protein-folding capacity while supporting proteasomal degradation of misfolded ER proteins. IRE1α elaborates these functions by deploying its cytoplasmic kinase-RNase module to activate the transcription factor XBP1s. The validity of IRE1α as a potential therapeutic target in MM has been questioned. Using genetic and pharmacologic disruption in vitro and in vivo, we demonstrate that the IRE1α-XBP1s pathway plays a critical role in MM growth. We further show that IRE1α’s kinase domain is an effective and safe potential small-molecule target for MM therapy.
Identifying the Biosynthetic Gene Cluster for Triacsins with anN-hydroxytriazene Moiety
Authors: Twigg Frederick F. , Cai Wenlong , Huang Wei , Liu Joyce , Sato Michio , Perez Tynan J. , Geng Jiaxin , Dror Moriel J. , Montanez Ismael , Tong Tate L. , Lee Hyunsu , Zhang Wenjun 
Published: December 2018

AbstractTriacsins are a family of natural products containing an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, the biosynthesis of triacsins has remained unknown. Here, we report the identification of the triacsin biosynthetic gene cluster inStreptomyces aureofaciensATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producerStreptomyces tsukubaensisNRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performedin vivoto advance the understanding of N-hydroxytriazene biosynthesis.
Sustainability of spatially distributed bacteria-phage systems
Authors: Eriksen Rasmus Skytte , Mitarai Namiko , Sneppen Kim 
Published: December 2018

AbstractVirulent phages can expose their bacterial hosts to devastating epidemics, in principle opening for a complete elimination of their hosts. Although experiments indeed confirm large reduction of susceptible bacteria, there is no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modeling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how the spatial separation of initial bacterial positions and the self-protection of bacteria growing in spherical colonies favor bacterial survival. This suggest that spatial structures on the millimeter scale plays an important role in maintaining microbial diversity.
Genealogical distances under low levels of selection
Authors: Huss Elisabeth , Pfaffelhuber Peter 
Published: December 2018

AbstractFor a panmictic population of constant size evolving under neutrality, Kingman’s coalescent describes the genealogy of a population sample in equilibrium. However, for genealogical trees under selection, not even expectations for most basic quantities like height and length of the resulting random tree are known. Here, we give an analytic expression for the distribution of the total tree length of a sample of sizenunder low levels of selection in a two-alleles model. We can prove that trees are shorter than under neutrality under genic selection and if the beneficial mutant has dominanceh< 1/2, but longer forh> 1/2. The difference from neutrality is 𝒪 (α2) for genic selection with selection intensityαand 𝒪 (α) for other modes of dominance.
RAD-sequencing for estimating GRM-based heritability in the wild: a case study in roe deer
Authors: Gervais L , Perrier C , Bernard M , Merlet J , Pemberton J , Pujol B , Quéméré E 
Published: December 2018

AbstractEstimating the evolutionary potential of quantitative traits and reliably predicting responses to selection in wild populations are important challenges in evolutionary biology. The genomic revolution has opened up opportunities for measuring relatedness among individuals with precision, enabling pedigree-free estimation of trait heritabilities in wild populations. However, until now, most quantitative genetic studies based on a genomic relatedness matrix (GRM) have focused on long-term monitored populations for which traditional pedigrees were also available, and have often had access to knowledge of genome sequence and variability. Here, we investigated the potential of RAD-sequencing for estimating heritability in a free-ranging roe deer population for which no prior genomic resources were available. We propose a step-by-step analytical framework to optimize the quality and quantity of the genomic data and explore the impact of the SNP calling and filtering processes on the GRM structure and GRM-based heritability estimates. As expected, our results show that sequence coverage strongly affects the number of recovered loci, the genotyping error rate and the amount of missing data. Ultimately, this had little effect on heritability estimates and their standard errors, provided that the GRM was built from a minimum number of loci (above 7000). GRM-based heritability estimates thus appear robust to a moderate level of genotyping errors in the SNP dataset. We also showed that quality filters, such as the removal of low-frequency variants, affect the relatedness structure of the GRM, generating lower h2 estimates. Our work illustrates the huge potential of RAD-sequencing for estimating GRM-based heritability in virtually any natural population.
Rapid Determination of Antibiotic Susceptibility by Stimulated Raman Scattering Imaging of D2O Metabolism
Authors: Hong Weili , Cheng Ji-Xin 
Published: December 2018

AbstractRapid antibiotic susceptibility testing (AST) is urgently needed for treating infections with correct antibiotics and slowing down the emergence of antibiotic resistant bacteria. Current clinical methods reply on culture and take at least 16 h. Here, using P. aeruginosa, E. coli and S. aureus as models, we show that the AST can be finished in 10 minutes by stimulated Raman scattering (SRS) imaging of D2O metabolic activities. The metabolic incorporation of D2O, which is used for biomolecule synthesis, can be monitored in a single bacterium. Time lapse experiments show that the C-D vibrational signal can be observed in a single bacterium within 10 minutes culture in D2O medium. Since water is universally used for biosynthesis in bacteria, SRS imaging of D2O metabolism has the potential to be generalizable to different bacteria species.
Commentary: do brands compete or coexist?
Authors: Aaker David 
Published: December 2018

Purpose
A response to Sheth and Koschmann’s Do brands compete or coexist? How persistence of brand loyalty segments the market.

Design/methodology/approach
This paper is a comment piece written in response to Sheth and Koschmann’s “Do brands compete or coexist? How persistence of brand loyalty segments the market”.

Findings
In their article, Sheth and Koschmann’s position on brand competition reinforces the view that vigorous and costly competitive initiative designed to lure customers from one brand to another are futile in nature. Brand loyalty is too high. This note outlines that the only way to grow a business is to create “must haves” that define subcategories, manage these subcategories to success and build structural barriers to inhibit competition from gaining relevance. A firm’s focus on maintaining existing customers is a sound investment, but attempting to seek growth through attracting customers of competitors will not create growth.

Originality/value
This response to Sheth and Koschmann’s paper provides a scholarly dialogue centered upon the premise of brand loyalty within the context of market competition.
Comments on “Do brands compete or co-exist?”
Authors: Tellis Gerard J. 
Published: December 2018

Purpose
This commentary aims to enrich and contextualize the paper by Sheth and Koschmann, “Do Brands Compete or Coexist?” How persistence of brand loyalty segments the market.

Design/methodology/approach
This paper is a comment piece written in response to Sheth and Koschmann’s “Do brands compete or coexist? How persistence of brand loyalty segments the market”.

Findings
In their article, Sheth and Koschmann present some fascinating insights on competition in mature markets and the concept of brand loyalty, offering three novel hypotheses. However, while the manner in which their findings are stated is novel, the fact that brand loyalty is strong is not new. This note outlines several comments upon the research, three caveats and five opportunities for future research in the area. While Sheth and Koschmann’s approach is novel, their results are not altogether new and their research needs to be related to prior findings on brand loyalty across the canon.

Originality/value
This response to Sheth and Koschmann’s paper provides a scholarly dialogue centered upon the premise of brand loyalty within the context of market competition.
Low Copeptin Levels in Patients With Intradialytic Hypotension
Authors: Korucu Berfu , Helvaci Ozant , Ozbas Burak , Yeter Hasan , Yuce Deniz , Elbeg Sehri , Derici Ulver 
Published: December 2018

AbstractIntradialytic hypotension (IDH) is related to high morbidity and mortality. There is evidence that arginine‐vasopressin (AVP) responses could play a role. Copeptin is a reliable biomarker of AVP. In this study, copeptin, aldosterone, epinephrine, and norepinephrine levels in patients with IDH were evaluated throughout a hemodialysis (HD) session and compared with the control group. The study includes 15 patients who were normotensive during HD and 15 patients with IDH with a minimum HD vintage of 1 year. Blood samples were collected before the initiation of an HD session (T0), in the mid‐session for control group, 30 min after mean arterial pressure drop for IDH patients (T1), and at the end of the session (T2). Groups had similar demographic features and health parameters, interdialytic weight gains, and ultrafiltration amounts. The IDH group had a mean arterial pressure decline of 39.9 (±6.4) mm Hg. Copeptin levels of the control group increased an average of 79.9 (±97.5) pmol/L at T1 and an additional 24.8 (±33.9) pmol/L at T2. In the IDH group, copeptin level increases at T1 and T2 were 3.2 (±5.5) pmol/L and 34 (±44.6) pmol/L, respectively. Copeptin levels of the IDH group were significantly lower at T1 (P < 0.001) and at the T0–T2 interval than control group (P = 0.05). In the control group, aldosterone levels distinctly decreased, and in the IDH group, aldosterone levels were elevated (P < 0.001). Small changes were detected in epinephrine and norepinephrine levels for both groups but did not reach significance (P = 0.6 and P = 0.3, respectively). Lower copeptin level alterations suggest inadequate AVP responses in patients with IDH.
Association of Asian mitochondrial DNA haplogroup B with new development of knee osteoarthritis in Koreans
Authors: Koo Bon San , Song Yoonah , Lee Seunghun , Sung Yoon‐Kyoung , Shin Kyoung‐Jin , Cho Nam H. , Jun Jae‐Bum 
Published: December 2018

AbstractAimThe aim of this study was to determine which mitochondrial DNA (mtDNA) haplogroup is associated with new development of knee osteoarthritis (OA).MethodsEpidemiologic data and knee radiographs with the Kellgren‐Lawrence (K/L) score of the Ansung cohort study were prospectively obtained from the 2nd (2005‐2006) and 6th follow‐up periods (2013‐2014). The mtDNA was analyzed by multiplex mutagenetically separated polymerase chain reaction to determine Asian mtDNA haplogroups (M, G, D, D4, D5, M7, M8, M9, M10, N, A, N9, R, F and B). The frequency of the mtDNA haplogroup was compared between participants with knee OA (K/L score ≥2 or total knee replacement arthroplasty [OA group]) and those without knee OA (K/L < 2 [control group]) at the 6th follow‐up. Multiple logistic regression was used to determine the relative risk (RR) of mtDNA haplogroups for OA by adjusting for sex, age, body mass index, smoking and metabolic syndrome.ResultsThere were 1115 participants with epidemiological data, knee radiographs and DNA samples. Of these, 572 participants had a K/L score of 0 at the 2nd follow up, and 438 underwent knee radiography at the 6th follow up. Among the 438 participants, 160 were classified as having knee OA, and 278 were classified as the control group. The haplogroup B showed a significantly higher frequency in the OA group than in the control group (unadjusted RR = 1.794, P = 0.030; adjusted RR = 2.389, P = 0.004).ConclusionOur data suggest that mtDNA haplogroup B contributed to the new development of knee OA in Koreans.
A convolutional neural network for detecting sea turtles in drone imagery
Authors: Gray Patrick C. , Fleishman Abram B. , Klein David J. , McKown Matthew W. , Bézy Vanessa S. , Lohmann Kenneth J. , Johnston David W. 
Published: December 2018

Abstract

Marine megafauna are difficult to observe and count because many species travel widely and spend large amounts of time submerged. As such, management programmes seeking to conserve these species are often hampered by limited information about population levels.

Unoccupied aircraft systems (UAS, aka drones) provide a potentially useful technique for assessing marine animal populations, but a central challenge lies in analysing the vast amounts of data generated in the images or video acquired during each flight. Neural networks are emerging as a powerful tool for automating object detection across data domains and can be applied to UAS imagery to generate new population‐level insights. To explore the utility of these emerging technologies in a challenging field setting, we used neural networks to enumerate olive ridley turtles Lepidochelys olivacea in drone images acquired during a mass‐nesting event on the coast of Ostional, Costa Rica.

Results revealed substantial promise for this approach; specifically, our model detected 8% more turtles than manual counts while effectively reducing the manual validation burden from 2,971,554 to 44,822 image windows. Our detection pipeline was trained on a relatively small set of turtle examples (N = 944), implying that this method can be easily bootstrapped for other applications, and is practical with real‐world UAS datasets.

Our findings highlight the feasibility of combining UAS and neural networks to estimate population levels of diverse marine animals and suggest that the automation inherent in these techniques will soon permit monitoring over spatial and temporal scales that would previously have been impractical.
Challenges and solutions for analysing dual RNA‐seq data for non‐model host–pathogen systems
Authors: O'Keeffe Kayleigh R. , Jones Corbin D. 
Published: December 2018

Abstract

Dual RNA‐seq simultaneously profiles the transcriptomes of a host and of a pathogen during infection and may reveal the mechanisms underlying host–pathogen interactions. Dual RNA‐seq is inherently a mixture of transcripts from at least two species (host and pathogen), so this mixture must be computationally sorted into host and pathogen components. Sorting relies on aligning reads to respective reference genomes, which may be unavailable for both species in non‐model host–pathogen pairs. This lack of genomic resources may present challenges to applying dual RNA‐seq to non‐model systems.

We assessed the accuracy of alignments of dual RNA‐seq when using the genomic resources of a closely related species to the species of interest by simulating datasets of mixed transcripts from a host and pathogen. Specifically, we compared how different aligners performed across different proportions of pathogen‐to‐host transcripts and across variation in the genetic distance between the pathogen genome and reference genome. We performed extensive analyses for a host plant with a fungal pathogen, and then, we extended the plant–fungus results by repeating key analyses in vertebrate (human)–fungus and vertebrate–bacterium systems.

Aligners that were able to map pathogen transcripts to the reference genome of a species closely related to the pathogen (a ‘related reference genome’) also mismapped transcripts originating from the host to the pathogen's related reference genome. This resulted in regions where this occurred being quantified as overexpressed. If a host reference genome was available, we show that, to minimize host transcript mismapping and retain the ability to map pathogen transcripts, one could concatenate the host genome with the pathogen's related reference genome, then map transcripts to the concatenated genomes. If a host genome was unavailable, assembling reads de novo prior to aligning substantially decreased host read mismapping, while retaining the ability to map pathogen transcripts to a related reference genome.

The application of dual RNA‐seq to organisms without reference genomes is currently limited. We propose an analytical workflow that leverages the genomic resources of species closely related to species of interest to facilitate the application of dual RNA‐seq to reveal the mechanisms of host–pathogen interactions across a wider array of systems.