bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainties in νp-process nucleosynthesis from Monte Carlo variation of reaction rates
Authors: Nishimura (西村信哉) N , Rauscher T , Hirschi R , Cescutti G , Murphy A St J , Fröhlich C 
Published: July 2019

ABSTRACT
It has been suggested that a νp-process can occur when hot, dense, and proton-rich matter is expanding within a strong flux of antineutrinos. In such an environment, proton-rich nuclides can be produced in sequences of proton captures and (n, p) reactions, where the free neutrons are created in situ by $\overline{\nu }_\mathrm{e}+\mathrm{p} {\rightarrow} \mathrm{n}+\mathrm{e}^+$ reactions. The detailed hydrodynamic evolution determines where the nucleosynthesis path turns off from N = Z line and how far up the nuclear chart it runs. In this work, the uncertainties on the final isotopic abundances stemming from uncertainties in the nuclear reaction rates were investigated in a large-scale Monte Carlo approach, simultaneously varying more than 10 000 reactions. A large range of model conditions was investigated because a definitive astrophysical site for the νp-process has not yet been identified. The present parameter study provides, for each model, identification of the key nuclear reactions dominating the uncertainty for a given nuclide abundance. As all rates appearing in the νp-process involve unstable nuclei, and thus only theoretical rates are available, the final abundance uncertainties are larger than those for nucleosynthesis processes closer to stability. Nevertheless, most uncertainties remain below a factor of 3 in trajectories with robust nucleosynthesis. More extreme conditions allow production of heavier nuclides but show larger uncertainties because of the accumulation of the uncertainties in many rates and because the termination of nucleosynthesis is not at equilibrium conditions. It is also found that the solar ratio of the abundances of 92Mo and 94Mo could be reproduced within uncertainties.
Extensive transcriptional responses are co-ordinated by microRNAs as revealed by Exon–Intron Split Analysis (EISA)
Authors: Pillman Katherine A , Scheer Kaitlin G , Hackett-Jones Emily , Saunders Klay , Bert Andrew G , Toubia John , Whitfield Holly J , Sapkota Sunil , Sourdin Laura , Pham Hoang , Le Thuc D , Cursons Joseph , Davis Melissa J , Gregory Philip A , Goodall Gregory J , Bracken Cameron P 
Published: July 2019

AbstractEpithelial–mesenchymal transition (EMT) has been a subject of intense scrutiny as it facilitates metastasis and alters drug sensitivity. Although EMT-regulatory roles for numerous miRNAs and transcription factors are known, their functions can be difficult to disentangle, in part due to the difficulty in identifying direct miRNA targets from complex datasets and in deciding how to incorporate ‘indirect’ miRNA effects that may, or may not, represent biologically relevant information. To better understand how miRNAs exert effects throughout the transcriptome during EMT, we employed Exon–Intron Split Analysis (EISA), a bioinformatic technique that separates transcriptional and post-transcriptional effects through the separate analysis of RNA-Seq reads mapping to exons and introns. We find that in response to the manipulation of miRNAs, a major effect on gene expression is transcriptional. We also find extensive co-ordination of transcriptional and post-transcriptional regulatory mechanisms during both EMT and mesenchymal to epithelial transition (MET) in response to TGF-β or miR-200c respectively. The prominent transcriptional influence of miRNAs was also observed in other datasets where miRNA levels were perturbed. This work cautions against a narrow approach that is limited to the analysis of direct targets, and demonstrates the utility of EISA to examine complex regulatory networks involving both transcriptional and post-transcriptional mechanisms.
Cyclic oligoadenylate signalling mediates Mycobacterium tuberculosis CRISPR defence
Authors: Grüschow Sabine , Athukoralage Januka S , Graham Shirley , Hoogeboom Tess , White Malcolm F 
Published: July 2019

Abstract
The CRISPR system provides adaptive immunity against mobile genetic elements (MGE) in prokaryotes. In type III CRISPR systems, an effector complex programmed by CRISPR RNA detects invading RNA, triggering a multi-layered defence that includes target RNA cleavage, licencing of an HD DNA nuclease domain and synthesis of cyclic oligoadenylate (cOA) molecules. cOA activates the Csx1/Csm6 family of effectors, which degrade RNA non-specifically to enhance immunity. Type III systems are found in diverse archaea and bacteria, including the human pathogen Mycobacterium tuberculosis. Here, we report a comprehensive analysis of the in vitro and in vivo activities of the type III-A M. tuberculosis CRISPR system. We demonstrate that immunity against MGE may be achieved predominantly via a cyclic hexa-adenylate (cA6) signalling pathway and the ribonuclease Csm6, rather than through DNA cleavage by the HD domain. Furthermore, we show for the first time that a type III CRISPR system can be reprogrammed by replacing the effector protein, which may be relevant for maintenance of immunity in response to pressure from viral anti-CRISPRs. These observations demonstrate that M. tuberculosis has a fully-functioning CRISPR interference system that generates a range of cyclic and linear oligonucleotides of known and unknown functions, potentiating fundamental and applied studies.
CRISPR DNA elements controlling site-specific spacer integration and proper repeat length by a Type II CRISPR–Cas system
Authors: Kim Jenny G , Garrett Sandra , Wei Yunzhou , Graveley Brenton R , Terns Michael P 
Published: July 2019

AbstractCRISPR–Cas systems provide heritable immunity against viruses by capturing short invader DNA sequences, termed spacers, and incorporating them into the CRISPR loci of the prokaryotic host genome. Here, we investigate DNA elements that control accurate spacer uptake in the type II-A CRISPR locus of Streptococcus thermophilus. We determined that purified Cas1 and Cas2 proteins catalyze spacer integration with high specificity for CRISPR repeat junctions. We show that 10 bp of the CRISPR leader sequence is critical for stimulating polarized integration preferentially at the repeat proximal to the leader. Spacer integration proceeds through a two-step transesterification reaction where the 3′ hydroxyl groups of the spacer target both repeat borders on opposite strands. The leader-proximal end of the repeat is preferentially targeted for the first site of integration through recognition of sequences spanning the leader-repeat junction. Subsequently, second-site integration at the leader-distal end of the repeat is specified by multiple determinants including a length-defining mechanism relying on a repeat element proximal to the second site of integration. Our results highlight the intrinsic ability of type II Cas1/Cas2 proteins to coordinate directional and site-specific spacer integration into the CRISPR locus to ensure precise duplication of the repeat required for CRISPR immunity.
Citrus exocortis viroid causes ribosomal stress in tomato plants
Authors: Cottilli Patrick , Belda-Palazón Borja , Adkar-Purushothama Charith Raj , Perreault Jean-Pierre , Schleiff Enrico , Rodrigo Ismael , Ferrando Alejandro , Lisón Purificación 
Published: July 2019

AbstractViroids are naked RNAs that do not code for any known protein and yet are able to infect plants causing severe diseases. Because of their RNA nature, many studies have focused on the involvement of viroids in RNA-mediated gene silencing as being their pathogenesis mechanism. Here, the alterations caused by the Citrus exocortis viroid (CEVd) on the tomato translation machinery were studied as a new aspect of viroid pathogenesis. The presence of viroids in the ribosomal fractions of infected tomato plants was detected. More precisely, CEVd and its derived viroid small RNAs were found to co-sediment with tomato ribosomes in vivo, and to provoke changes in the global polysome profiles, particularly in the 40S ribosomal subunit accumulation. Additionally, the viroid caused alterations in ribosome biogenesis in the infected tomato plants, affecting the 18S rRNA maturation process. A higher expression level of the ribosomal stress mediator NAC082 was also detected in the CEVd-infected tomato leaves. Both the alterations in the rRNA processing and the induction of NAC082 correlate with the degree of viroid symptomatology. Taken together, these results suggest that CEVd is responsible for defective ribosome biogenesis in tomato, thereby interfering with the translation machinery and, therefore, causing ribosomal stress.
Molecular affinity rulers: systematic evaluation of DNA aptamers for their applicabilities in ELISA
Authors: Kimoto Michiko , Shermane Lim Yun Wei , Hirao Ichiro 
Published: July 2019

Abstract
Many nucleic acid aptamers that bind to target molecules have been reported as antibody alternatives. However, while the affinities of aptamers vary widely, little is known about the relationship between the affinities and their applicabilities for practical use. Here, we developed molecular affinity rulers: a series of DNA aptamers with different affinities that bind to the same area of target molecules, to measure the aptamer and its device applicabilities. For the ruler preparation, we used high-affinity DNA aptamers containing a hydrophobic unnatural base (Ds) as the fifth base. By replacing Ds bases with A bases in Ds-DNA aptamers targeting VEGF165 and interferon-γ, we prepared two sets of DNA aptamers with dissociation constants (KD) ranging from 10−12 to 10−8 M. Using these molecular affinity rulers, we evaluated the sensitivity of DNA aptamers in ELISA (enzyme-linked immunosorbent assay), which showed the clear relationship between aptamer affinities and their detection sensitivities. In sandwich-type ELISA using combinations of aptamers and antibodies, aptamers with KD values lower than ∼10−9 M were required for sufficient sensitivities (limit of detection (LOD) &lt; 10 pM) and signal intensities, but optimizations improved the lower-affinity aptamers’ applicabilities. These aptamer affinity rulers could be useful for evaluating and improving aptamer applicabilities.
Telomerase RNAs in land plants
Authors: Fajkus Petr , Peška Vratislav , Závodník Michal , Fojtová Miloslava , Fulnečková Jana , Dobias Šimon , Kilar Agata , Dvořáčková Martina , Zachová Dagmar , Nečasová Ivona , Sims Jason , Sýkorová Eva , Fajkus Jiří 
Published: July 2019

Abstract
To elucidate the molecular nature of evolutionary changes of telomeres in the plant order Asparagales, we aimed to characterize telomerase RNA subunits (TRs) in these plants. The unusually long telomere repeat unit in Allium plants (12 nt) allowed us to identify TRs in transcriptomic data of representative species of the Allium genus. Orthologous TRs were then identified in Asparagales plants harbouring telomere DNA composed of TTAGGG (human type) or TTTAGGG (Arabidopsis-type) repeats. Further, we identified TRs across the land plant phylogeny, including common model plants, crop plants, and plants with unusual telomeres. Several lines of functional testing demonstrate the templating telomerase function of the identified TRs and disprove a functionality of the only previously reported plant telomerase RNA in Arabidopsis thaliana. Importantly, our results change the existing paradigm in plant telomere biology which has been based on the existence of a relatively conserved telomerase reverse transcriptase subunit (TERT) associating with highly divergent TRs even between closely related plant taxa. The finding of a monophyletic origin of genuine TRs across land plants opens the possibility to identify TRs directly in transcriptomic or genomic data and/or predict telomere sequences synthesized according to the respective TR template region.
Insights into the base-pairing preferences of 8-oxoguanosine on the ribosome
Authors: Thomas Erica N , Simms Carrie L , Keedy Hannah E , Zaher Hani S 
Published: July 2019

AbstractOf the four bases, guanine is the most susceptible to oxidation, which results in the formation of 8-oxoguanine (8-oxoG). In protein-free DNA, 8-oxodG adopts the syn conformation more frequently than the anti one. In the syn conformation, 8-oxodG base pairs with dA. The equilibrium between the anti and syn conformations of the adduct are known to be altered by the enzyme recognizing 8-oxodG. We previously showed that 8-oxoG in mRNA severely disrupts tRNA selection, but the underlying mechanism for these effects was not addressed. Here, we use miscoding antibiotics and ribosome mutants to probe how 8-oxoG interacts with the tRNA anticodon in the decoding center. Addition of antibiotics and introduction of error-inducing mutations partially suppressed the effects of 8-oxoG. Under these conditions, rates and/or endpoints of peptide-bond formation for the cognate (8-oxoG•C) and near-cognate (8-oxoG•A) aminoacyl-tRNAs increased. In contrast, the antibiotics had little effect on other mismatches, suggesting that the lesion restricts the nucleotide from forming other interactions. Our findings suggest that 8-oxoG predominantly adopts the syn conformation in the A site. However, its ability to base pair with adenosine in this conformation is not sufficient to promote the necessary structural changes for tRNA selection to proceed.
Open chromatin structure in PolyQ disease-related genes: a potential mechanism for CAG repeat expansion in the normal human population
Authors: Sorek Matan , Cohen Lea R Z , Meshorer Eran 
Published: July 2019

Abstract
The human genome contains dozens of genes that encode for proteins containing long poly-glutamine repeats (polyQ, usually encoded by CAG codons) of 10Qs or more. However, only nine of these genes have been reported to expand beyond the healthy variation and cause diseases. To address whether these nine disease-associated genes are unique in any way, we compared genetic and epigenetic features relative to other types of genes, especially repeat containing genes that do not cause diseases. Our analyses show that in pluripotent cells, the nine polyQ disease-related genes are characterized by an open chromatin profile, enriched for active chromatin marks and depleted for suppressive chromatin marks. By contrast, genes that encode for polyQ-containing proteins that are not associated with diseases, and other repeat containing genes, possess a suppressive chromatin environment. We propose that the active epigenetic landscape support decreased genomic stability and higher susceptibility for expansion mutations.
When Does the Personal Vote Matter for Party Loyalty? The Conditional Effects of Candidate-Centred Electoral Systems
Authors: Carroll Royce , Nalepa Monika 
Published: July 2019

Abstract
When do candidate-centred electoral systems produce undisciplined parties? In this article, we examine party discipline under open-list proportional representation, a system associated with MPs cultivating personal constituencies. We present a model explaining how legislators’ preferences and support among voters mediate political leaders’ ability to enforce discipline. We show that disloyalty in candidate-centred systems depends on parties’ costs for enforcing discipline, but only conditional on MP preferences. MPs who share the policy preferences of their leaders will be loyal even when the leaders cannot discipline them. To test the model’s implications, we use data on legislative voting in Poland’s parliament. Our empirical findings confirm that disloyalty is conditioned on party leaders’ enforcement capacity and MP preferences. We find that legislators who contribute more to the party electorally in terms of votes are more disloyal, but only if their preferences diverge from the leadership. Our results suggest that the relationship between open lists and party disloyalty is conditional on the context of the party system.
Association Between Chiropractic Use and Opioid Receipt Among Patients with Spinal Pain: A Systematic Review and Meta-analysis
Authors: Corcoran Kelsey L , Bastian Lori A , Gunderson Craig G , Steffens Catherine , Brackett Alexandria , Lisi Anthony J 
Published: July 2019

Abstract

Objective
To investigate the current evidence to determine if there is an association between chiropractic use and opioid receipt.

Design
Systematic review and meta-analysis.

Methods
The protocol for this review was registered on PROSPERO (CRD42018095128). The MEDLINE, PubMed, EMBASE, AMED, CINAHL, and Web of Science databases were searched for relevant articles from database inception through April 18, 2018. Controlled studies, cohort studies, and case–control studies including adults with noncancer pain were eligible for inclusion. Studies reporting opioid receipt for both subjects who used chiropractic care and nonusers were included. Data extraction and risk of bias assessment were completed independently by pairs of reviewers. Meta-analysis was performed and presented as an odds ratio with 95% confidence interval.

Results
In all, 874 articles were identified. After detailed selection, 26 articles were reviewed in full, and six met the inclusion criteria. Five studies focused on back pain and one on neck pain. The prevalence of chiropractic care among patients with spinal pain varied between 11.3% and 51.3%. The proportion of patients receiving an opioid prescription was lower for chiropractic users (range = 12.3–57.6%) than nonusers (range = 31.2–65.9%). In a random-effects analysis, chiropractic users had a 64% lower odds of receiving an opioid prescription than nonusers (odds ratio = 0.36, 95% confidence interval = 0.30–0.43, P < 0.001, I2 = 92.8%).

Conclusions
This review demonstrated an inverse association between chiropractic use and opioid receipt among patients with spinal pain. Further research is warranted to assess this association and the implications it may have for case management strategies to decrease opioid use.
Supporting Policy Reform from the Outside
Authors: Smets Lodewijk 
Published: July 2019

AbstractSound economic and social policies are important if countries wish to prosper and achieve sustainable development. It is far from guaranteed, however, that policymakers select and implement good policies, which provides a rationale for external policy support. Indeed, many organizations are engaged in supporting policy reform processes in recipient countries. This study investigates the limits and opportunities of supporting policy reform by focusing on four dimensions of support: conditional financing, policy dialogue, technical evidence and political institutions. Four findings follow from a review of the literature. First, without commitment on the recipient side, conditional financing is unlikely to induce policy reform. Second, when external actors acquire a seat at the policy dialogue table, it is important to detect (and influence) the beliefs policymakers hold. Third, outside parties should bring sound evidence to the table about the costs, benefits, and effectiveness of their policy proposals. Finally, supporting changes in political institutions without considering general equilibrium effects can be counterproductive. The study concludes with a discussion and some avenues for future research in this field.
XIII The Victorian Period
Authors: Garza Ana Alicia , Burke Lois , Dickinson Christian , Williams Helen , Barnes Lucy , Baker William 
Published: July 2019

AbstractThis chapter has six sections: 1. General and Prose; 2. The Novel; 3. Poetry; 4. Periodicals and Publishing History; 5. Drama; 6. Miscellaneous and Cross-Genre. Section 1 is by Ana Alicia Garza; section 2 is by Lois Burke with assistance from Christian Dickinson, who writes on Dickens; section 3 is by Ana Alicia Garza; section 4 is by Helen Williams; section 5 is by Lucy Barnes; section 6 is by William Baker. Thanks for assistance with this chapter must go to Dominic Edwards, Steven Amarnick, Richard Bleiler, Nancy S. Weyant, the bibliographer of Mrs Gaskell, and Patrick Scott.In a departure from previous years, and in order to avoid confusion as to who has contributed what to this chapter, George Borrow, Thomas and Jane Welsh Carlyle, and Richard Jefferies, previously found in the General and Prose section, and the Brontës, Samuel Butler, Wilkie Collins, George Eliot, George Henry Lewes, George Gissing, and Anthony Trollope, previously found in the Novel section, will be found in section 6, Miscellaneous and Cross-Genre, as will materials that came in too late to be included in other sections.
Back-to-Back Surgeries in AIS Patients Can be Performed Safely Without Compromising Radiographic or Perioperative Outcomes
Authors: Sarwahi Vishal , Galina Jesse , Wendolowski Stephen , Ganz Maximillian , Hasan Sayyida , Katyal Chhavi , Moguilevitch Marina , DiMauro Jon-Paul , Lo Yungtai , Amaral Terry D. 
Published: July 2019

Study Design.
A retrospective chart review of prospectively collected data.

Objective.
The aim of this study was to determine whether back-to-back scoliosis surgeries can be performed safely without compromising outcomes and the reproducibility of the practice between institutions.

Summary of Background Data.
During the summer, spinal surgeons will often book multiple cases in one day. The complexity and demands of spinal fusion surgery call into question the safety. Change of operating room staff including anesthesiologists, nurses, and neurologists may introduce new risks.

Methods.
From 2009 to 2018, index AIS surgeries were included. In Groups 1, 2, and 3, surgeries were performed by a single surgeon. In Group 4, they were performed by other institutional surgeons. Group 1: first surgery of the day, Group 2: second surgery of the day, Group 3: only surgery of the day, Group 4: only surgery of the day by different institutional surgeon. Additional analysis was done to determine reproducibility after a surgeon was moved from Institution 1 to Institution 2.

Results.
Five hundred sixty-seven AIS patients were analyzed. Group 1 patients had similar radiographic outcomes compared with Group 2 (P > 0.05). Surgical time was similar (P = 0.51), but significantly more levels fused (P = 0.01). Compared with Group 3, Group 2 had a smaller preoperative Cobb (P = 0.02), shorter surgeries (P < 0.001), and length of stay (P = 0.04) but similar complication rate (P = 1). Compared with Group 4, Group 2 had smaller preoperative Cobb (P < 0.001), shorter surgery, and lower complication rate (P = 0.03). When determining reproducibility, institution 2 patients had significantly less blood loss, shorter surgeries, and shorter lengths of stay (P < 0.05).

Conclusion.
Although long and involved, back-to-back AIS surgeries do not compromise radiographic or perioperative outcomes. Changes in operating team do not appear to impact safety, efficiency, or outcomes. This study also found that the practice is reproducible between institutions.

Level of Evidence: 3