bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake and Impact of Short Message Service Reminders via Sexually Transmitted Infection Partner Services on Human Immunodeficiency Virus/Sexually Transmitted Infection Testing Frequency Among Men Who Have Sex With Men
Authors: Ronen Keshet , Golden Matthew R. , Dombrowski Julia C. , Kerani Roxanne P. , Bell Teal R. , Katz David A. 
Published: July 2019

Background
Sexually transmitted infection (STI) partner services (PS) allow provision of human immunodeficiency virus (HIV)/STI prevention interventions to high-risk individuals, including testing reminders via short message service (SMS).

Methods
In King County, Washington, PS attempt to reach all men who have sex with men (MSM) with early syphilis and those with gonorrhea or chlamydia as resources allow. Since 2013, PS offered quarterly SMS testing reminders. We evaluated correlates of reminder uptake and the association between reminder uptake and postinterview asymptomatic STI diagnosis using Poisson regression, and the association between preinterview SMS reminder use and intertest interval among HIV-negative MSM using median regression.

Results
During July 1, 2013 to January 17, 2018, 8236 MSM were reported with 1 or more STI diagnoses and 5237 received PS interviews. Of these, 4087 (78%) were offered SMS reminders; 545 (13%) accepted, 265 (7%) were already receiving SMS, 3277 (80%) refused. Of 2602 patients who refused and were asked about other reminders, 37% used none, 16% received reminders from medical providers, 20% tested at routine physicals, and 26% used other reminders. SMS reminder use before and after PS interview was associated with negative HIV status, younger age, and diagnosis with gonorrhea or chlamydia (vs. syphilis) (P < 0.05 for all). Preinterview intertest interval was longer among MSM testing at physicals (9.6 months) than those using no reminder (5.6), SMS reminders (4.7, P < 0.05 vs. physicals), and non-SMS reminders (3.6, P < 0.001 vs. SMS). Reminder uptake was not associated with postinterview STI diagnosis.

Conclusions
Offering SMS reminders through STI PS is feasible. Uptake was low, but higher among young MSM not on preexposure prophylaxis. The SMS reminders may increase testing frequency.
DIfferential Subsampling With Cartesian Ordering With Respiratory Triggering Versus Conventional Liver Acquisition With Volume Acquisition: A Multiple Reader Preference Study
Authors: Allen Brian C. , Ehieli Wendy L. , Wildman-Tobriner Benjamin , Chaudhry Mohammad , Bozdogan Erol , Janas Gemini , Ronald James , Bashir Mustafa R. 
Published: July 2019

Objective
The aim of this study was to compare respiratory-triggered DIfferential Subsampling with Cartesian Ordering (rtDISCO) and breath-held Liver Acquisition with Volume Acquisition (LAVA) image quality.

Methods
In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant prospective study, 25 subjects underwent T1 imaging with rtDISCO and LAVA before and after intravenous contrast. Three readers scored individual series and side-by-side comparisons for motion and noise. Eight clinical tasks were qualitatively assessed.

Results
As individual series, readers rated rtDISCO images as more degraded by motion on both precontrast (mean rtDISCO score, 2.7; LAVA, 1.6; P < 0.001) and postcontrast images (rtDISCO, 2.4; LAVA, 1.8; P < 0.001). Readers preferred LAVA images based on motion on both precontrast (mean preference, −1.2; P < 0.001) and postcontrast images (mean preference, −0.7; P < 0.001) on side-by-side assessment. There was no preference between sequences for 6 of 8 clinical tasks on postcontrast images.

Conclusions
Readers preferred LAVA with respect to motion but not noise; there was no preference in most of the tested clinical tasks.
A horizontally acquired expansin gene increases virulence of the emerging plant pathogenErwinia tracheiphila
Authors: Rocha Jorge , Shapiro Lori R. , Kolter Roberto 
Published: July 2019

AbstractAll land plants depend on proteins called ‘expansins’ that non-enzymatically loosen structural cellulose, enabling cell wall extension during normal growth. Surprisingly, expansin genes are also present – but functionally uncharacterized – in taxonomically diverse bacteria and fungi that do not produce cellulosic cell walls. Here, we find thatErwinia tracheiphila(Enterobacteriaceae), the causative agent of bacterial wilt of cucurbits, has horizontally acquired an operon with a microbial expansin (exlx) gene and a glycoside hydrolase family 5 (gh5) gene.E. tracheiphilais an unusually virulent plant pathogen that induces systemic wilt symptoms followed by plant death, and has only recently emerged into cultivated cucurbit populations in temperate Eastern North America. Plant inoculation experiments with deletion mutants show that EXLX-GH5 is a secreted virulence factor that confers efficient xylem movement and colonization ability toE. tracheiphila. Bacterial colonization of xylem blocks sap flow, inducing wilt symptoms and causing plant death. Together, these results suggest that the horizontal acquisition of theexlx-gh5locus was likely a key step driving the recent emergence ofE. tracheiphila. The increase inE. tracheiphilavirulence conferred by microbial expansins, the presence of this gene in many other bacterial and fungal wilt-inducing plant pathogen species, and the amenability of microbial expansins to horizontal gene transfer suggest this gene may be an under-appreciated virulence factor in taxonomically diverse agricultural pathogens.ImportanceErwinia tracheiphilais a bacterial plant pathogen that causes a fatal wilt infection in cucurbit crop plants. Here, we report thatE. tracheiphilahas horizontally acquired a microbial expansin gene (exlx) adjacent to a glycoside hydrolase family 5 (gh5) gene. Expansins are predominantly associated with plants due to their essential role in loosening structural cell wall cellulose during normal growth. We find that the EXLX and GH5 proteins inE. tracheiphilafunction as a single complex to facilitate xylem colonization, possibly by manipulating the size of xylem structures that normally exclude the passage of bacteria. This suggests that horizontal acquisition of theexlx-gh5locus was likely a key step in the recent emergence ofE. tracheiphilaas an unusually virulent plant pathogen. The presence of microbial expansin genes in diverse species of bacterial and fungal wilt-inducing pathogens suggests it may be an under-appreciated virulence factor for other microbes.
In silico karyotyping of chromosomally polymorphic malaria mosquitoes in theAnopheles gambiaecomplex
Authors: Love R. Rebecca , Redmond Seth N. , Pombi Marco , Caputo Beniamino , Petrarca Vincenzo , della Torre Alessandra ,   The Anopheles gambiae 1000 Genomes Consortium, Besansky Nora J. 
Published: July 2019

AbstractChromosomal inversion polymorphisms play an important role in adaptation to environmental heterogeneities. For mosquito species in theAnopheles gambiaecomplex that are significant vectors of human malaria, paracentric inversion polymorphisms are abundant and are associated with ecologically and epidemiologically important phenotypes. Improved understanding of these traits relies on determining mosquito karyotype, which currently depends upon laborious cytogenetic methods whose application is limited both by the requirement for specialized expertise and for properly preserved adult females at specific gonotrophic stages. To overcome this limitation, we developed sets of tag SNPs inside inversions whose biallelic genotype is strongly correlated with inversion genotype. We leveraged 1,347 fully sequencedAn. gambiaeandAnopheles coluzziigenomes in the Ag1000G database of natural variation. Beginning with principal components analysis (PCA) of population samples, applied to windows of the genome containing individual chromosomal rearrangements, we classified samples into three inversion genotypes, distinguishing homozygous inverted and homozygous uninverted groups by inclusion of the small subset of specimens in Ag1000G that are associated with cytogenetic metadata. We then assessed the correlation between candidate tag SNP genotypes and PCA-based inversion genotypes in our training sets, selecting those candidates with >80% agreement. Our initial tests both in held-back validation samples from Ag1000G and in data independent of Ag1000G suggest that when used forin silicoinversion genotyping of sequenced mosquitoes, these tags perform better than traditional cytogenetics, even for specimens where only a small subset of the tag SNPs can be successfully ascertained.
Presynaptic mitochondria volume and abundance increase during development of a high-fidelity synapse
Authors: Thomas Connon I. , Keine Christian , Okayama Satoko , Satterfield Rachel , Musgrove Morgan , Guerrero-Given Debbie , Kamasawa Naomi , Young Samuel M. 
Published: July 2019

AbstractThe calyx of Held, a large glutamatergic presynaptic terminal in the auditory brainstem undergoes developmental changes to support the high action-potential firing rates required for auditory information encoding. In addition, calyx terminals are morphologically diverse which impacts vesicle release properties and synaptic plasticity. Mitochondria influence synaptic plasticity through calcium buffering and are crucial for providing the energy required for synaptic transmission. Therefore, it has been postulated that mitochondrial levels increase during development and contribute to the morphological-functional diversity in the mature calyx. However, the developmental profile of mitochondrial volumes and subsynaptic distribution at the calyx of Held remains unclear. To provide insight on this, we developed a helper-dependent adenoviral vector (HdAd) that expresses the genetically encoded peroxidase marker for mitochondria, mito-APEX2, at the mouse calyx of Held. We developed protocols to detect labeled mitochondria for use with serial block face scanning electron microscopy to carry out semi-automated segmentation of mitochondria, high-throughput whole terminal reconstruction and presynaptic ultrastructure in mice of either sex. Subsequently, we measured mitochondrial volumes and subsynaptic distributions at the immature postnatal day 7 (P7) and the mature (P21) calyx. We found an increase of mitochondria volumes in terminals and axons from P7 to P21 but did not observe differences between stalk and swelling subcompartments in the mature calyx. Based on these findings, we propose that mitochondrial volumes and synaptic localization developmentally increase to support high firing rates required in the initial stages of auditory information processing.Significance StatementElucidating the developmental processes of auditory brainstem presynaptic terminals is critical to understanding auditory information encoding. Additionally, morphological-functional diversity at these terminals is proposed to enhance coding capacity. Mitochondria provide energy for synaptic transmission and can buffer calcium, impacting synaptic plasticity; however, their developmental profile to ultimately support the energetic demands of synapses following the onset of hearing remains unknown. Therefore, we created a helper-dependent adenoviral vector with the mitochondria-targeting peroxidase mito-APEX2 and expressed it at the mouse calyx of Held. Volumetric reconstructions of serial block face electron microscopy data of immature and mature labeled calyces reveal that mitochondrial volumes are increased to support high firing rates upon maturity.
Automated methods enable direct computation on phenotypic descriptions for novel candidate gene prediction
Authors: Braun Ian R. , Lawrence-Dill Carolyn J. 
Published: July 2019

1AbstractNatural language descriptions of plant phenotypes are a rich source of information for genetics and genomics research. We computationally translated descriptions of plant phenotypes into structured representations that can be analyzed to identify biologically meaningful associations. These repre-sentations include the EQ (Entity-Quality) formalism, which uses terms from biological ontologies to represent phenotypes in a standardized, semantically-rich format, as well as numerical vector representations generated using Natural Language Processing (NLP) methods (such as the bag-of-words approach and document embedding). We compared resulting phenotype similarity measures to those derived from manually curated data to determine the performance of each method. Computationally derived EQ and vector representations were comparably successful in recapitulating biological truth to representations created through manual EQ statement curation. Moreover, NLP methods for generating vector representations of phenotypes are scalable to large quantities of text because they require no human input. These results indicate that it is now possible to computationally and automatically produce and populate large-scale information resources that enable researchers to query phenotypic descriptions directly.
Mutations beget more mutations – The baseline mutation rate and runaway accumulation
Authors: Ruan Yongsen , Chen Bingjie , Chen Qingjian , Wen Haijun , Wu Chung-I 
Published: July 2019

AbstractThere is a sizable literature on mutation rate evolution (Drake 1991; Makova and Li 2002; Lynch 2011; Scally and Durbin 2012; Sung, et al. 2012) but few studies incorporate the recent genomic data from somatic tissues that suggest the operation of mutators. These data show that the mutation burden among cancer samples may vary by several orders of magnitude (Kandoth, et al. 2013; Lawrence, et al. 2013). We now propose a runaway model, applicable to both the germline and the soma, whereby the accumulation of mutator mutations forms a positive-feedback loop. In this loop, any mutator mutation would increase the probability of acquiring the next mutator, thus triggering a runaway escalation in mutation rate. The process can be initiated more readily if there are many weak, rather than a few strong, mutators. Interestingly, even a small increase in the mutation rate at birth could trigger the runaway process, resulting in unfit progeny in slowly reproducing species. In such species, the need to minimize the risk of this uncontrolled accumulation would entail a mutation rate that may seem unnecessarily low. In comparison, species that starts and ends reproduction much sooner do not face the risk and may set the baseline mutation rate higher. The mutation rate would evolve as the generation time changes, therefore explaining many puzzling evolutionary phenomena (Elango, et al. 2006; Thomas, et al. 2010; Langergraber, et al. 2012; Thomas, et al. 2018; Besenbacher, et al. 2019).
Integrating NMR and Simulations Reveals Motions in the UUCG Tetraloop
Authors: Bottaro Sandro , Nichols Parker J. , Vögeli Beat , Parrinello Michele , Lindorff-Larsen Kresten 
Published: July 2019

AbstractWe provide an atomic-level description of the structure and dynamics of the UUCG RNA stem-loop by combining molecular dynamics simulations with experimental data. The integration of simulations with exact nuclear Overhauser enhancements data allowed us to characterize two distinct states of this molecule. The most stable conformation corresponds to the consensus three-dimensional structure. The second state is characterized by the absence of the peculiar non-Watson-Crick interactions in the loop region. By using machine learning techniques we identify a set of experimental measurements that are most sensitive to the presence of non-native states. We find that although our MD ensemble, as well as the consensus UUCG tetraloop structures, are in good agreement with experiments, there are remaining discrepancies. Together, our results show that i) the structural interpretation of experimental data for dynamic RNAs is highly complex, even for a simple model system such as the UUCG tetraloop ii) the MD simulation overstabilize a non-native loop conformation, and iii) eNOE data support its presence with a population of ≈10%.
HNF1A recruits UTX to activate a differentiation program that suppresses pancreatic cancer
Authors: Kalisz Mark , Bernardo Edgar , Beucher Anthony , Maestro Miguel Angel , del Pozo Natalia , Millán Irene , Haeberle Lena , Schlensog Martin , Safi Sami Alexander , Knoefel Wolfram Trudo , Grau Vanessa , de Vas Matías , Shpargel Karl B. , Vaquero Eva , Magnuson Terry , Ortega Sagrario , Esposito Irene , Real Francisco X. , Ferrer Jorge 
Published: July 2019

AbstractDefects in transcriptional regulators of pancreatic exocrine differentiation have been implicated in pancreatic tumorigenesis, but the molecular mechanisms are poorly understood. The locus encoding the transcription factor HNF1A harbors susceptibility variants for pancreatic ductal adenocarcinoma (PDAC), while KDM6A, encoding the histone demethylase UTX, carries somatic mutations in PDAC. Here, we show that pancreas-specific Hnf1a null mutations phenocopy Utx deficient mutations, and both synergize with KrasG12D to cause PDAC with sarcomatoid features. We combine genetic, epigenomic and biochemical studies to show that HNF1A recruits UTX to genomic binding sites in pancreatic acinar cells. This remodels the acinar enhancer landscape, activates a differentiation program, and indirectly suppresses oncogenic and epithelial-mesenchymal transition genes. Finally, we identify a subset of non-classical PDAC samples that exhibit the HNF1A/UTX-deficient molecular phenotype. These findings provide direct genetic evidence that HNF1A-deficiency promotes PDAC. They also connect the tumor suppressive role of UTX deficiency with a cell-specific molecular mechanism that underlies PDAC subtype definition.
The Cu(II) reductase RclA protectsEscherichia coliagainst the combination of hypochlorous acid and intracellular copper
Authors: Derke Rhea M. , Barron Alexander J. , Billiot Caitlin E. , Chaple Ivis F. , Lapi Suzanne E. , Broderick Nichole A. , Gray Michael J. 
Published: July 2019

ABSTRACTInflammatory bowel diseases (IBDs) are a growing health concern. Enterobacteria, includingEscherichia coli, bloom to high levels in the gut during inflammation and strongly contribute to the pathology of IBDs. To survive in the inflamed gut,E. colimust tolerate high levels of antimicrobial compounds produced by the immune system, including toxic metals like copper and reactive chlorine oxidants like hypochlorous acid (HOCl). In this work, we show that the widely-conserved bacterial HOCl resistance enzyme RclA catalyzes the reduction of copper (II) to copper (I), and specifically protectsE. coliagainst the combination of HOCl and intracellular copper, probably by preventing Cu(III) accumulation.E. colilacking RclA were highly sensitive to HOCl and were defective in colonizing an animal host. Our results indicate unexpected complexity in the interactions between antimicrobial toxins produced by innate immune cells and suggest an important and previously unsuspected role for copper redox reactions during inflammation.
Frequency but not phase specific modulation of binocular rivalry with transcranial alternating current stimulation
Authors: Delgado Jorge , Riesen Guillaume , Vildavski Vladimir Y. , Norcia Anthony M. 
Published: July 2019

ABSTRACTRecent transcranial alternating current stimulation (tACS) literature suggests that tACS effects can in principle be both frequency and phase specific. In a series of three experiments using 69 participants used binocular rivalry percepts as a read-out for the effects of phase-synchronized tACS stimulation. To test for phase specificity, with frequency the same in each eye, we visually stimulated each eye with 3Hz, with stimuli in each eye presented in temporal in antiphase. The frequency-specific paradigm visually stimulated the right eye with 3Hz, and the left eye with 5Hz. Each experiment was accompanied by 3Hz tACS, whose phase with respect to the visual stimulus was varied by 0°, 90°, 180°, or 270° in relation to the right eye’s stimulus. A baseline no-tACS block preceded the stimulation blocks and two more followed, immediately and ten minutes after. Individual blocks lasted 4 minutes. Additionally, a no-tACS control experiment identical to the 3 Hz anti-phase visual stimuli setup was conducted, keeping all parameters the same but eliminating tACS. During stimulation, the 3 Hz anti-phase visual stimuli setup slowed the rate of rivalry in both eyes. Conversely, the 3Hz-right, 5Hz-left setup slowed the right (targeted) eye significantly while leaving the left (unstimulated) eye unchanged. In both experiments, durations returned to baseline after 10 minutes. Our results are consistent with the frequency-specific model of tACS, and with the Leveltian hypothesis that stimulation weakens the stimulated eye, as the right eye got weaker when it was directly targeted, and both eyes got weaker when targeted in antiphase. tACS does not appear to preferentially modulating percept durations in one phase more than in another.
Druggable genome screen identifies new regulators of the abundance and toxicity of ATXN3, the Spinocerebellar Ataxia Type 3 disease protein
Authors: Ashraf Naila S. , Sutton Joanna R. , Yang Yemen , Ranxhi Bedri , Libohova Kozeta , Shaw Emily D. , Barget Anna J. , Todi Sokol V. , Paulson Henry L. , Costa Maria do Carmo 
Published: July 2019

AbstractBackgroundSpinocerebellar Ataxia type 3 (SCA3, also known as Machado-Joseph disease) is a neurodegenerative disorder caused by a CAG repeat expansion encoding an abnormally long polyglutamine (polyQ) tract in the disease protein, ataxin-3 (ATXN3). No preventive treatment is yet available for SCA3. Because SCA3 is likely caused by a toxic gain of ATXN3 function, a rational therapeutic strategy is to reduce mutant ATXN3 levels by targeting pathways that control its production or stability. Here, we sought to identify genes that modulate ATXN3 levels as potential therapeutic targets in this fatal disorder.MethodsWe screened a collection of siRNAs targeting 2742 druggable human genes using a cell-based assay based on luminescence readout of polyQ-expanded ATXN3. From 317 candidate genes identified in the primary screen, 100 genes were selected for validation. Among the 33 genes confirmed in secondary assays, 15 were validated in an independent cell model as modulators of pathogenic ATXN3 protein levels. Ten of these genes were then assessed in aDrosophilamodel of SCA3, and one was confirmed as a key modulator of physiological ATXN3 abundance in SCA3 neuronal progenitor cells.ResultsAmong the 15 genes shown to modulate ATXN3 in mammalian cells, orthologs ofCHD4,FBXL3,HRandMC3Rregulate mutant ATXN3-mediated toxicity in fly eyes. Further mechanistic studies of one of these genes,FBXL3, encoding a F-box protein that is a component of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex, showed that it reduces levels of normal and pathogenic ATXN3 in SCA3 neuronal progenitor cells, primarily via a SCF complex-dependent manner. Bioinformatic analysis of the 15 genes revealed a potential molecular network with connections to tumor necrosis factor-α/nuclear factor-kappa B (TNF/NF-kB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways.ConclusionsWe identified 15 druggable genes with diverse functions to be suppressors or enhancers of pathogenic ATXN3 abundance. Among identified pathways highlighted by this screen, the FBXL3/SCF axis represents a novel molecular pathway that regulates physiological levels of ATXN3 protein.