bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous polyploids and antimutators compete during the evolution of mutator cells
Authors: Tracy Maxwell A. , Lee Mitchell B. , Hearn Brady L. , Dowsett Ian T. , Thurber Luke C. , Loo Jason , Loeb Anisha M. , Preston Kent , Tuncel Miles I. , Ghodsian Niloufar , Bode Anna , Tang Thao T. , Chia Andy R. , Herr Alan J. 
Published: July 2019

AbstractHeterozygous mutations affecting DNA polymerase (Pol) exonuclease domains and homozygous inactivation of mismatch repair (MMR) each generate “mutator” phenotypes capable of driving tumorigenesis. Cancers with both defects exhibit an explosive increase in mutation burden that appears to reach a threshold, consistent with selection acting against further mutation accumulation. In haploid yeast, simultaneous defects in polymerase proofreading and MMR select for “antimutator” mutants that suppress the mutator phenotype. We report here that spontaneous polyploids also escape this “error-induced extinction” and routinely out-compete antimutators in evolved haploid cultures. We performed similar experiments to explore how diploid yeast adapt to the mutator phenotype. We first evolved cells with homozygous mutations affecting proofreading and MMR, which we anticipated would favor tetraploid emergence. While tetraploids arose with a low frequency, in most cultures, a single antimutator clone rose to prominence carrying biallelic mutations affecting the polymerase mutator alleles. Variation in mutation rate between subclones from the same culture suggests there exists continued selection pressure for additional antimutator alleles. We then evolved diploid yeast modeling MMR-deficient cancers with the most common heterozygous exonuclease domain mutation (POLE-P286R). Although these cells grew robustly, within 120 generations, all subclones carried truncating or nonsynonymous mutations in thePOLE-P286Rhomologous allele (pol2-P301R) that suppressed the mutator phenotype as much as 100-fold. Independent adaptive events in the same culture were common. Our findings suggest that analogous tumor cell populations may adapt to the threat of extinction by polyclonal mutations that neutralize thePOLEmutator allele and preserve intra-tumoral genetic diversity for future adaptation.
Rural populations exposed to Ebola Virus Disease respond positively to localised case handling: evidence from Sierra Leone
Authors: Mokuwa Esther Yei , Maat Harro 
Published: July 2019

AbstractAt the height of the Ebola epidemic in Sierra Leone in November 2014, a new decentralized approach to ending infection chains was adopted. This approach was based on building local, small-scale Community Care Centres (CCC) intended to serve as triage units for safe handling of patients waiting for test results, with subsequent transfer to Ebola Treatment Centers (ETC) for those who tested positive for Ebola. This paper deals with local response to the CCC, and explores, through qualitative analysis of focus group data sets, why communities see CCC in a positive light. The responses of 562 focus group participants in seven villages with CCC and seven neighbouring control villages without CCC are assessed. These data confirm that CCC are compatible with community values concerning access to, and family care for, the sick. Mixed reactions are reported in the case of “safe burial”, a process that directly challenged ritual activity seen as vital to maintaining good relations between socially-enclaved rural families. Land acquisitions to build CCC prompted divided responses. This reflects problems about land ownership unresolved since colonial times between communities and government. The study provides insights into how gaps in understanding between international Ebola responders and local communities can be bridged.Author SummaryControl of Ebola Virus Disease requires facilities where patients can be isolated and treated safely, without risk to medical personnel or family members. In the 2014-15 Ebola epidemic in Sierra Leone emphasis was at first placed on large field hospitals known as Ebola Treatment Centers (ETC). These were often located far from areas where new cases were being discovered. Patients were distrustful of their purpose and slow to report, and the disease continued to spread. Six months into the epidemic a new approach was tried, based on much smaller and more rapidly constructed centres (Community Care Centres (CCC) located where new cases were occurring. This paper examines community reactions to the CCC. There was a much greater sense of community ownership of these small, localised centres, and reporting times improved. Families were able easily to visit and observe activities, even though restricted from crossing red lines. The staff were often local and provided trustworthy information on the progress of patients. Families were able to prepare home food for patients, and this was thought to improve their morale and chances of survival. CCC were also appreciated for treating other disease, and not only Ebola. Referral of patients to ETC was easier to accept when the outcome of an Ebola blood test was known. There were some differences of opinion over “safe burial” procedures and acquisition of sites for the CCC, but on balance CCC were well accepted by communities, and were seen locally as a positive development in Ebola control.
Expression of telomerase prevents ALT and maintains telomeric heterochromatin in juvenile brain tumors
Authors: Idilli Aurora Irene , Cusanelli Emilio , Pagani Francesca , Kerschbamer Emanuela , Berardinelli Francesco , Bernabé Manuel , Cayuela María Luisa , Piazza Silvano , Poliani Pietro Luigi , Mione Maria Caterina 
Published: July 2019

ABSTRACTThe activation of a telomere maintenance mechanism (TMM) is an essential step in cancer progression to escape replicative senescence and apoptosis. Paediatric brain tumors frequently exhibit Alternative Lengthening of Telomere (ALT) as active TMM, but the mechanisms involved in the induction of ALT in brain tumor cells are not clear.Here, we report a model of juvenile zebrafish brain tumor that progressively develops ALT. We discovered that reduced expression of tert and increase in Terra expression precedes ALT development. Additionally, tumors show persistent telomeric DNA damage and loss of heterochromatin marks at chromosome ends. Surprisingly, expression of telomerase reverts ALT features. Comparative analysis of gene expression after the rescue of ALT with telomerase and analysis of telomerase positive paediatric brain cancers showed increase of telomeric heterochromatin and maintenance of telomere length compared to ALT tumors, with reduced expression of genes of the pre-replicative complex as hallmark. Thus our study identifies telomere maintenance mechanisms as major drivers of telomeric DNA replication and chromatin status in brain cancers.
Delineation of post-phloem assimilate transport pathway into developing caryopsis of Brachypodium distachyon
Authors: Solomon Charles Ugochukwu , Drea Sinead 
Published: July 2019

AbstractAssimilates stored in mature cereal grains are mobilized from source tissues and transported towards developing grains through the vascular bundle. Due to the lack of direct vascular connection between maternal grain vascular bundle and filial tissues, post-phloem transportation of assimilates into grain endosperm relies on transfer cells that lie between the grain vascular bundle and the endosperm. Here, we propose Caryopsis Endosperm Assimilate Acquisition Route (CEAAR) models that describes the exact path of assimilate import into caryopsis endosperms. Using fluorescent tracer dyes we also delineated the route of assimilate delivery into Brachypodium distachyon endosperm and classified it as ventral circuitous (vc-CEAAR), an assimilate import model also found in rice. Furthermore, we report a detailed anatomical study of post-phloem assimilate transport pathway in developing grains of Brachypodium distachyon. Our results highlight major anatomical similarities and differences between the grain post-phloem transfer cells of Brachypodium and those of crop species such as rice, wheat, and barley relevant to post-phloem assimilate transport.HighlightsBased on existing work, we propose Caryopsis Endosperm Assimilate Acquisition Route (CEAAR) models, that describes the exact path of assimilate import into caryopsis endosperms.The structure of the post-phloem transfer cells of Brachypodium distachyon mirrors temperate and tropical cereals.Assimilate delivery into Brachypodium distachyon endosperm is identical to assimilate import into rice endosperm.
Towards standardization of immune functional assays
Authors: Mouton William , Vega Chloé Albert , Boccard Mathilde , Bartolo François , Oriol Guy , Lopez Jonathan , Pachot Alexandre , Textoris Julien , Mallet François , Brengel-Pesce Karen , Trouillet-Assant Sophie 
Published: July 2019

AbstractRecent advances in the immunotherapy field require evaluation of the immune function to adapt therapeutic decisions. Immune functional assays (IFA) are able to reveal the immune status and would be useful to further adapt/improve patient’s care. However, standardized methods are needed to implement IFA in clinical settings. We carried out an independent validation of a published method used to characterize the underlying host response to infectious conditions using an IFA. We evaluate the reproducibility and robustness of this IFA and associated readout using an independent healthy volunteers (HV) cohort. Expression of a 44 genes-signatures and IFNγ protein secretion and gene-expression was assessed after stimulation. We observed a strong host-response correlation between the two cohorts. We also highlight that standardized methods for immune function evaluation exist and could be implemented in larger-scale studies. This IFA could be a relevant tool to reveal innate/adaptive immune dysfunction in immune-related disorders patients.
An Escherichia coli ST131 pangenome atlas reveals population structure and evolution across 4,071 isolates
Authors: Decano Arun Gonzales , Downing Tim 
Published: July 2019

AbstractEscherichia coli ST131 is a major cause of infection with extensive antimicrobial resistance (AMR) facilitated by widespread beta-lactam antibiotic use. This drug pressure has driven extended-spectrum beta-lactamase (ESBL) gene acquisition and evolution in pathogens, so a clearer resolution of ST131’s origin, adaptation and spread is essential. E. coli ST131’s ESBL genes are typically embedded in mobile genetic elements (MGEs) that aid transfer to new plasmid or chromosomal locations, which are mobilised further by plasmid conjugation and recombination, resulting in a flexible ESBL, MGE and plasmid composition with a conserved core genome. We used population genomics to trace the evolution of AMR in ST131 more precisely by extracting all available high-quality Illumina HiSeq read libraries to investigate 4,071 globally-sourced genomes, the largest ST131 collection examined so far. We applied rigorous quality-control, genome de novo assembly and ESBL gene screening to resolve ST131’s population structure across three genetically distinct Clades (A, B, C) and abundant subclades from the dominant Clade C. We reconstructed their evolutionary relationships across the core and accessory genomes using published reference genomes, long read assemblies and k-mer-based methods to contextualise pangenome diversity. The three main C subclades have co-circulated globally at relatively stable frequencies over time, suggesting attaining an equilibrium after their origin and initial rapid spread. This contrasted with their ESBL genes, which had stronger patterns across time, geography and subclade, and were located at distinct locations across the chromosomes and plasmids between isolates. Within the three C subclades, the core and accessory genome diversity levels were not correlated due to plasmid and MGE activity, unlike patterns between the three main clades, A, B and C. This population genomic study highlights the dynamic nature of the accessory genomes in ST131, suggesting that surveillance should anticipate genetically variable outbreaks with broader antibiotic resistance levels. Our findings emphasise the potential of evolutionary pangenomics to improve our understanding of AMR gene transfer, adaptation and transmission to discover accessory genome changes linked to novel subtypes.
Calcium-permeable AMPA receptors mediate timing-dependent LTP elicited by low repeat coincident pre- and postsynaptic activity at Schaffer collateral-CA1 synapses
Authors: Cepeda-Prado Efrain A. , Khodaie Babak , Quiceno Gloria D. , Beythien Swantje , Edelmann Elke , Lessmann Volkmar 
Published: July 2019

AbstractHigh-frequency stimulation induced long-term potentiation (LTP), or low frequency stimulation induced LTD are considered as cellular models of memory formation. Interestingly, spike timing-dependent plasticity (STDP) can induce equally robust timing-dependent LTP (t-LTP) and t-LTD in response to low frequency repeats of coincident action potential (AP) firing in presynaptic and postsynaptic cells. Commonly, STDP paradigms relying on 25-100 repeats of coincident AP firing are used to elicit t-LTP or t-LTD, but the minimum number of repeats required for successful STDP is barely explored. However, systematic investigation of physiologically relevant low repeat STDP paradigms is of utmost importance to explain learning mechanisms in vivo. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1 t-LTP), or a burst of 4 APs (1:4 t-LTP) and found 3-6 repeats to be sufficient to elicit t-LTP. 6x 1:1 t-LTP required postsynaptic Ca2+ influx via NMDARs and L-type VGCCs and was mediated by increased presynaptic glutamate release. In contrast, 1:4 t-LTP depended on postsynaptic metabotropic GluRs and ryanodine receptor signaling, and was mediated by postsynaptic insertion of AMPA receptors. Unexpectedly, both 6x t-LTP variants were strictly dependent on activation of postsynaptic Ca2+-permeable AMPARs but were differentially regulated by dopamine receptor signaling. Our data show that synaptic changes induced by only 3-6 repeats of mild STDP stimulation occurring in ≤ 10 s can take place on time scales observed also during single trial learning.
Neural crest cells bulldoze through the microenvironment using Aquaporin-1 to stabilize filopodia
Authors: McLennan Rebecca , McKinney Mary C. , Teddy Jessica M. , Morrison Jason A. , Kasemeier-Kulesa Jennifer C. , Ridenour Dennis A. , Manthe Craig A. , Giniunaite Rasa , Robinson Martin , Baker Ruth E. , Maini Philip K. , Kulesa Paul M. 
Published: July 2019

ABSTRACTNeural crest migration requires cells to move through an environment filled with dense extracellular matrix and mesoderm to reach targets throughout the vertebrate embryo. Here, we use high-resolution microscopy, computational modeling, and in vitro and in vivo cell invasion assays to investigate the function of Aquaporin-1 (AQP-1) signaling. We find that migrating lead cranial neural crest cells express AQP-1 mRNA and protein, implicating a biological role for water channel protein function during invasion. Differential AQP-1 levels affect neural crest cell speed, direction, and the length and stability of cell filopodia. Further, AQP-1 enhances matrix metalloprotease (MMP) activity and colocalizes with phosphorylated focal adhesion kinases (pFAK). Co-localization of AQP-1 expression with EphB guidance receptors in the same migrating neural crest cells raises novel implications for the concept of guided bulldozing by lead cells during migration.
Pseudomonas can survive bacteriocin-mediated killing via a persistence-like mechanism
Authors: Kandel PP , Baltrus David A. , Hockett Kevin L. 
Published: July 2019

AbstractPhage tail-like bacteriocins (tailocins) are bacterially-produced protein toxins that can mediate competitive interactions between co-colonizing bacteria. Both theoretical and empirical research has shown there are intransitive interactions between bacteriocin-producing, bacteriocin-sensitive, and bacteriocin-resistant populations, whereby producers outcompete sensitive, sensitive outcompete resistant, and resistant outcompete producers. These so-called ‘rock-paper-scissor’ dynamics explain how all three populations can be maintained in the same environment, without one genotype driving the others extinct. Using Pseudomonas syringae as a model system, we demonstrate that otherwise sensitive bacterial cells have the ability to survive bacteriocin exposure through a physiological mechanism. This mechanism is similar to the persister phenotype that allows cells to survive antibiotic exposure, without acquiring antibiotic resistance. We show that a significant fraction of the target cells that survive a lethal dose of tailocin did not exhibit any detectable increase in survival in subsequent exposure (i.e. they survived through a persistence-like mechanism). Tailocin persister cells were more prevelant in stationary rather than log phase cultures. Of the fraction of cells that gained detectable tailocin resistance, there was a range of resistance from complete (insensitive) to incomplete (partially sensitive). By genomic sequencing and genetic engineering we showed that a mutation in a hypothetical gene containing 8-10 transmembrane domains causes tailocin high-persistence and genes of various glycosyl transferases cause incomplete and complete tailocin resistance. Importantly, of the several classes of mutations, only those causing complete tailocin resistance compromised host fitness. This result, combined with previous research, indicates that bacteria likely utilize persistence as a means to survive bacteriocin-mediated killing without suffering the costs associated with resistance. This research provides important insight into how bacteria can escape the trap of fitness trade-offs associated with gaining de novo tailocin resistance, and expands our understanding of how sensistive bacterial populations can persist in the presence of lethal competitors.
Rab28 is localised to photoreceptor outer segments, regulates outer segment shedding but is not linked to retinal degeneration in zebrafish
Authors: Carter Stephen P. , Moran Ailís L. , Matallanas David , McManus Gavin J. , Blacque Oliver E. , Kennedy Breandán N. 
Published: July 2019

AbstractThe photoreceptor outer segment is the canonical example of a modified and highly specialised cilium, with an expanded membrane surface area in the form of discs or lamellae for efficient light detection. Many ciliary proteins are essential for normal photoreceptor function and cilium dysfunction often results in retinal degeneration leading to impaired vision. Herein, we investigate the function and localisation of the ciliary G-protein RAB28 in zebrafish cone photoreceptors. CRISPR-Cas9 generated rab28 mutant zebrafish display a reduction in shed outer segment material in the RPE at 1 month post fertilisation (mpf), but otherwise normal retinal structure and visual function up to 12 mpf. Cone photoreceptor-specific transgenic reporter lines show Rab28 localises almost exclusively to outer segments, independently of nucleotide binding. Co-immunoprecipitation analysis demonstrates tagged Rab28 interacts with components of the phototransduction cascade, including opsins, Phosphodiesterase 6C and Guanylate Cyclase 2D. Our data shed light on RAB28 function in cones and provide a model for RAB28-associated cone-rod dystrophy.
Influence of milling toolpaths in machining of the turbine blade
Authors: Jarolmasjed Seyedamin , Davoodi Behnam , Pourebrahim Alamdari Babak 
Published: July 2019

PurposeThe purpose of this paper is to machine the pressure surface of the turbine blade made of A286 iron-based superalloy by using four directions of raster strategy, including horizontal upward, horizontal downward, vertical upward and vertical downward, to achieve appropriate surface roughness and to investigate the tool wear in each strategy.Design/methodology/approachIn this study, all cutting tests were performed by DAHLIH-MCV 1020 BA vertical 3-axis machining center with ball nose end mill. After milling by each strategy, according to the surface slope, the surface was divided into 27 meshes, and roughness of surface was studied and compared. Roughness measuring after machining was implemented by using portable Mahr ps1 roughness tester, and surface texture was photographed by CCD 100× optical zoom camera. Also, to measure tool flank wear in each strategy as an indication of tool life, the surface of workpiece was divided into four equal areas. The wear of the inserts was measured by ARCS vertical non-contact measuring system at the end of each area.FindingsThe results indicate that cutting directions and toolpath strategies have significant influence on tool wear and surface roughness in machining processes and that they can be taken into consideration individually as determinative parameters. In this case, the most uniform surface texture and the lowest surface roughness are obtained by using horizontal downward direction; in addition, abrasion is a dominant tool wear mechanism in all experiments, and tool wear in the horizontal downward is lower than other strategies.Practical implicationsMachining of turbine blades or other airfoil-shaped workpieces is quite common in manufacturing aerospace and aircraft products. The results of this research contribute to increasing quality of machined surface and tool life in machining of turbine blade.Originality/valueThis work proves the significance of milling strategies in machining of the turbine blade made of A286 superalloy and, consequently, exhibits the proper strategy in terms of surface roughness and tool life. Also, this work explains and elaborates the behavior of A286 superalloy in machining processes, which has not been studied much in recent research works.
“Hard to find”: information barriers among LGBT college students
Authors: Stewart Brenton , Kendrick Kaetrena Davis 
Published: July 2019

Purpose
The purpose of this paper is to examine collegiate information barriers and perceptions of academic library climate among lesbian, gay, bisexual and transgender (LGBT) college students in the USA.

Design/methodology/approach
The primary method used for this investigation was an online crowdsourced survey of 105 participants who attended two and four-year colleges in the USA. The questionnaire used free word association where participants shared information barriers encountered on colleges’ campuses. Responses from each questionnaire were interpreted using open coding.

Findings
Information barriers around sexuality continue to be a challenge for non- heteronormative information seekers on college campuses. One-third of students had distinctive information needs around their sexuality and experienced information barriers from both the institution and social stigma. The study reveals an evolution in sexual minority students’ sense of self, which has moved beyond the binary identity of gay/lesbian explored in previous studies; students identified bisexuality as a salient information need, and described a campus environment that often erased bisexuality. The academic library was described as an information barrier due to inadequate sexual minority-related resources.

Practical implications
Academic librarians as well as higher education professionals, such as recruitment/admissions officers, student counseling services, student health and student affairs, can leverage the results of this study to help establish a more inclusive and welcoming information environment that empowers students for academic and personal success.

Originality/value
A limited number of studies in information science have focused on sexual minority college students’ information behaviors and even fewer on information barriers. This study presents new insight and deeper understanding of the collegiate information environment of LGBT identified students in the USA.