bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Planting Date on Melanaphis sacchari (Hemiptera: Aphididae) Population Dynamics and Grain Sorghum Yield
Authors: Seiter Nicholas J , Miskelley Anne D , Lorenz Gus M , Joshi Neelendra K , Studebaker Glenn E , Kelley Jason P
Published: July 2019

The sugarcane aphid, Melanaphis sacchari (Zehntner) (Hemiptera: Aphididae), has become a major pest of grain sorghum, Sorghum bicolor (L.) Moench, in the United States in recent years. Feeding by large densities of sugarcane aphids causes severe damage, which can lead to a total loss of yield in extreme cases. Our objective was to determine the effect of grain sorghum planting date on sugarcane aphid population dynamics and their potential to reduce yields. We conducted field experiments from 2015 to 2017 in which an aphid-susceptible grain sorghum hybrid was planted at four different dates, which encompassed the typical range of planting dates used in Arkansas production systems. Plots were either protected from sugarcane aphid feeding using foliar insecticide sprays, or left untreated to allow natural populations of sugarcane aphids to colonize and reproduce freely. Planting date impacted both the magnitude and severity of sugarcane aphid infestations, with the highest population densities (and subsequent reductions in sorghum yield) generally occurring on plots that were planted in May or June. Sugarcane aphid feeding reduced yields in the untreated plots in two of the four planting date categories we tested. Earlier planting generally resulted in less sugarcane aphid damage and improved yields compared with later planting dates. While the effect of planting date on sugarcane aphid populations is likely to vary by region, sorghum producers should consider grain sorghum planting date as a potential cultural tactic to reduce the impact of sugarcane aphid.
Evaluation of Residue Levels of Imidacloprid and Thiamethoxam After Foliar Application to the Citrus Varieties Lane Late, Valencia Late, Rohde Summer, and Nules
Authors: Martínez-Ferrer María Teresa , Campos-Rivela José Miguel , Hernando-Guil María Dolores , García-Valcárcel Ana Isabel
Published: July 2019

Neonicotinoids are used to protect citrus trees against pests. Dissipation and persistence of neonicotinoids in pollen and nectar of citrus trees after foliar applications and their potential exposure to pollinators have not been well characterized. Field studies were conducted using three orange and one mandarin varieties to compare the imidacloprid and thiamethoxam residue levels and their decline in pollen and nectar after treatments in pre-bloom close to flowering period and their persistence 1 yr after treatment. The possible risk to honeybees was assessed. In nectar, thiamethoxam and imidacloprid residues were between 61 and 99% lower than in pollen, depending on the citrus variety or/and the days after treatment when applied close to blooming. At the end of the flowering period, imidacloprid in pollen and nectar was not detected in the mandarin variety after treatment in pre-bloom, whereas for thiamethoxam, no residues were detected in nectar but 10 ng/g was detected in pollen. There were no quantifiable levels of residues for either neonicotinoids in pollen or nectar during the flowering period of the following year. Neonicotinoid residue levels and their decline in nectar and pollen in citrus depended on the timing of applications relative to flowering and on the citrus variety. The absence of neonicotinoid residues 1 yr out after foliar applications in all varieties assayed demonstrated that none of the neonicotinoids tested were persistent. The results could be different in other citrus varieties, and therefore, also the exposure assessment for managed pollinators.
FTLD-TDP With and Without GRN Mutations Cause Different Patterns of CA1 Pathology
Authors: Mao Qinwen , Zheng Xiaojing , Gefen Tamar , Rogalski Emily , Spencer Callen L , Rademakers Rosa , Fought Angela J , Kohler Missia , Weintraub Sandra , Xia Haibin , Mesulam Marek-Marsel , Bigio Eileen H
Published: July 2019

Heterozygous loss-of-function mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A). PGRN is a highly conserved, secreted glycoprotein and functions in the central nervous system as a key modulator of microglial function. Hence, altered microglial function caused by PGRN deficiency may be tied to the pathogenesis of FTLD-TDP. Our previous studies showed that haploinsufficiency of GRN mutations extends to microglial PGRN expression in the hippocampal CA1 region. In this study, we found that the CA1 sector was associated with less neuronal loss and more frequent TDP-43 inclusions in FTLD-TDP type A cases with GRN mutations than in sporadic cases. In addition, the CA1 region in GRN mutation cases contained more rod-like microglia, which also had reduced PGRN expression. These findings suggest that the profile of TDP-43 inclusions, neuronal number, and microgliosis in the CA1 sector of FTLD-TDP type A cases may be influenced by GRN gene expression status.
Glioneuronal Tumor With Features of Ganglioglioma and Neurocytoma Arising in the Fourth Ventricle: A Report of 2 Unusual Cases and a Review of Infratentorial Gangliogliomas
Authors: Harrison William , Elsamadicy Aladine A , McMahon J Tanner , Chagoya Gustavo , Sobel Raymond A , McLendon Roger E , Adamson Cory
Published: July 2019

Infratentorial glioneuronal neoplasms are overall quite rare and are more commonly low-grade with surgical excision usually being curative. Multiple distinct histologic entities have been described including rosette-forming glioneuronal tumor, papillary glioneuronal tumor, neurocytoma, dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease), cerebellar liponeurocytoma, and ganglioglioma. While each of these entities has distinct findings, in some instances a tumor may demonstrate overlapping histologic features with mixed components. Herein, we report 2 unusual adult cases of a fourth ventricular glioneuronal tumor with features of ganglioglioma and neurocytoma, with one coming from a surgical resection and one found incidentally at autopsy. To the best of our knowledge, this specific histologic combination has not previously been described. As such, the clinical significance is unknown although in both cases the neoplasms were circumscribed and appeared to be low grade. The presence of the gangliogliomatous component was of particular interest since these are extremely rare occurrences in the fourth ventricle and we provide a comprehensive review of infratentorial gangliogliomas.
Use of Antimicrobial Agents in Hospitalized Children for Noninfectious Indications
Authors: Jaggi Preeti , Hamdy Rana F , Lee Brian , Hersh Adam L , Gerber Jeffrey S , Sharland Mike , Terrill Cindy , Newland Jason G
Published: July 2019

In this point-prevalence study of 32 US children’s hospitals, we determined that 1.7% of hospitalized children received at least 1 antimicrobial agent for a non–infection-related reason; macrolides were used most commonly. Antimicrobial stewardship efforts to understand and affect use for these reasons is an unmet need; additional research considering the individual and societal effects of these antimicrobial-prescribing practices should be undertaken.
Highly aggressive undifferentiated small round blue cell tumor of foot with unique SMARCA1, KAT6A and NAV3 mutations
Authors: Parsa Cyrus , Orlando Robert , Marcus Michael , Guo Jin , Rupani Ravin
Published: July 2019

Malignancies characterized histologically by high-grade monotonous small round blue cells (SRBCs) belong to a heterogeneous group of neoplasms often referred to as Ewing family of tumors. The most common molecular confirmation of these neoplasms is by fusions between EWSR1 gene on chromosome 22 and the ETS family of transcription factors, including FLI1 gene (11q24) and the ERG (21q22), that are implicated in the development of different tissues as well as cancer progression. In this article, we present a case of highly aggressive extraskeletal SRBC tumor involving the foot of a 24-year-old male with sole molecular findings of mutations in KAT6A, NAV3 and SMARCA1 genes with high expression of soft tissue markers (COL1A1, COL1A2, COL3A1) and MYC mRNA. To our knowledge, this unique mutational pattern has not previously been described in SRBCs.
Part I General Concepts, 2 The Three Models of the Concept of State Immunity
Authors: Hazel Fox , Philippa Webb
Published: July 2019

This chapter analyses the evolution and reformulation of international law principles of equality and independence and the consequent change in the extent of State immunity as a plea barring the bringing of proceedings against a foreign State in national courts via three models. The First Model, the absolute doctrine, is concerned with the immunity from proceedings in national courts by reason of the independent status of the foreign State; the Second Model, the restrictive doctrine, traces the limitation of immunity to the State's exercise of public powers as contrasted with its engagement in private relations; and the Third Model, immunity as a procedural exclusionary plea, looks at the recasting of immunity as a procedural exclusionary plea in the presentation of a claim against a foreign State in a national court.
Part II The Sources of the Law of State Immunity, 5 A Review of the Sources: Treaties and Projects for Codification
Authors: Hazel Fox , Philippa Webb
Published: July 2019

This chapter provides a list of the sources, both international and national, of the law of State immunity and a brief survey of relevant treaties and projects for codification in existence prior to the adoption in 2004 of the UN Convention on Jurisdictional Immunities of States and their Property (UNCSI). Accepting the sources of international law to be as summarized in Article 38(1) of the Statute of the International Court of Justice (ICJ), law-making international conventions are clearly the best source of the principles and rules relating to State immunity. Not until the twenty-first century was the law of State immunity accorded sufficient relevance for States to adopt an international convention dealing with the topic and for the issues which it raised to come before the ICJ.
Part IV Other Immunities, 18 Immunity of Individuals acting on behalf of the State
Authors: Hazel Fox , Philippa Webb
Published: July 2019

This chapter considers the immunities of individuals; including the head of State, head of government, the Foreign Minister, officials when on special missions, and other personnel in the service of the State to whom immunity is accorded. Immunity based on the nature of the act is sometimes called ratione materiae as compared to ratione personae, which is based on the status of the State that performs the act. But, given that, unlike the individual who may cease to serve, lapse of time is generally irrelevant to the State (who under the restrictive doctrine remains a State throughout), and in order to avoid confusion these terms are confined to immunity enjoyed by State officials.
The formation of habitable planets in the four-planet system HD 141399
Authors: Dvorak R , Loibnegger B , Zhou L Y , Zhou L
Published: July 2019

The presented work investigates the possible formation of terrestrial planets in the habitable zone (HZ) of the exoplanetary system HD 141399. In this system, the HZ is located approximately between the planets c (a  = 0.7 au) and d (a  = 2.1 au). Extensive numerical integrations of the equations of motion in the pure Newtonian framework of small bodies with different initial conditions in the HZ are performed. Our investigations included several steps starting with 500 massless bodies distributed between planets c and d in order to model the development of the disc of small bodies. It turns out that after some 106 yr, a belt-like structure analogue to the main belt inside Jupiter in our Solar system appears. We then proceed with giving the small bodies masses (∼ Moon mass) and take into account the gravitational interaction between these planetesimal-like objects. The growing of the objects – with certain percentage of water – due to collisions is computed in order to look for the formation of terrestrial planets. We observe that planets form in regions connected to mean motion resonances (MMR). So far there is no observational evidence of terrestrial planets in the system of HD 141399 but from our results we can conclude that the formation of terrestrial planets – even with an appropriate amount of water necessary for being habitable – in the HZ would have been possible.
Cyanoacetylene in the outflow/hot molecular core G331.512−0.103
Authors: Duronea N U , Bronfman L , Mendoza E , Merello M , Finger R , Reyes N , Hervías-Caimapo C , Faure A , Cappa C E , Arnal E M , Lépine J R D , Kleiner I , Nyman L-Å
Published: July 2019

Using APEX-1 and APEX-2 observations, we have detected and studied the rotational lines of the HC3N molecule (cyanoacetylene) in the powerful outflow/hot molecular core G331.512−0.103. We identified 31 rotational lines at J levels between 24 and 39; 17 of them in the ground vibrational state v = 0 (9 lines corresponding to the main C isotopologue and 8 lines corresponding to the 13C isotopologues), and 14 in the lowest vibrationally excited state v7 = 1. Using local thermodynamic equilibrium (LTE)-based population diagrams for the beam-diluted v = 0 transitions, we determined Texc = 85 ± 4 K and N(HC3N) = (6.9 ± 0.8) × 1014 cm−2, while for the beam-diluted v7 = 1 transitions we obtained Texc = 89 ± 10 K and N(HC3N) = (2 ± 1) × 1015 cm−2. Non-LTE calculations using H2 collision rates indicate that the HC3N emission is in good agreement with LTE-based results. From the non-LTE method, we estimated Tkin ≃90 K, n(H2) ≃ 2 × 107 cm−3 for a central core of 6 arcsec in size. A vibrational temperature in the range from 130 to 145 K was also determined, values which are very likely lower limits. Our results suggest that rotational transitions are thermalized, while infrared radiative pumping processes are probably more efficient than collisions in exciting the molecule to the vibrationally excited state v7 = 1. Abundance ratios derived under LTE conditions for the 13C isotopologues suggest that the main formation pathway of HC3N is C2H2 + CN → HC3N + H.
Origins of scaling relations of globular cluster systems
Authors: Choksi Nick , Gnedin Oleg Y
Published: July 2019

Globular cluster (GC) systems demonstrate tight scaling relations with the properties of their host galaxies. In previous work, we developed an analytic model for GC formation in a cosmological context that matches nearly all of these observed scaling relations. Here, we apply our model to investigate in detail the physical origins and evolution of these scaling relations. The ratio of the combined mass in GCs MGC to the host dark matter halo mass Mh is nearly constant at all redshifts, but its normalization evolves by a factor of ∼10 from birth to z = 0. The relation is steeper than linear at halo masses $M_{\mathrm{h}}\lesssim 10^{11.5}\, \mathrm{M}_{\odot }$, primarily due to non-linearity in the stellar mass–halo mass relation. The near constancy of the ratio MGC/Mh, combined with the shape of the stellar mass–halo mass relation, sets the characteristic U shape of the GC specific frequency as a function of host galaxy mass. The contribution of accreted satellite galaxies to the buildup of GC systems is a strong function of the host galaxy mass, ranging from ≈0 per cent at $M_{\mathrm{h}}\approx 10^{11} \, \mathrm{M}_{\odot }$ to 80 per cent at $M_{\mathrm{h}}\approx 10^{15} \, \mathrm{M}_{\odot }$. The metal-poor clusters are significantly more likely to form ex situ relative to the metal-rich clusters, but a substantial fraction of metal-poor clusters still form in situ in lower mass galaxies. Cluster formation occurs essentially continuously at high redshift, while at low redshift galactic mergers become increasingly important for cluster formation. Consequently, although major mergers form clusters efficiently, they are too rare to form most clusters.
Systematic errors in Gaia DR2 astrometry and their impact on measurements of internal kinematics of star clusters
Authors: Vasiliev Eugene
Published: July 2019

We use stellar proper motions (PM) from Gaia Data Release 2 for studying the internal kinematics of Milky Way globular clusters. In addition to statistical measurement errors, there are significant spatially correlated systematic errors, which cannot be ignored when studying the internal kinematics. We develop a mathematically consistent procedure for incorporating the spatial correlations in any model-fitting approach, and use it to determine rotation and velocity dispersion profiles of a few dozen clusters. We confirm detection of rotation in the sky plane for ∼10 clusters reported in previous studies, and discover a few more clusters with rotation amplitudes exceeding ∼0.05 mas yr−1. However, in more than half of these cases the significance of this rotation signature is rather low when taking into account the systematic errors. We find that the PM dispersion is not sensitive to systematic errors in PM, however, it is quite sensitive to the selection criteria on the input sample, most importantly, in crowded central regions. When using the cleanest possible samples, PM dispersion can be reliably measured down to 0.1 mas yr−1 for ∼60 clusters.
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

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

Epithelial–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

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

CRISPR–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

Viroids 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

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) < 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

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

Of 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

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

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

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.
Positivity of Divisor Classes on the Strata of Differentials
Authors: Chen Dawei
Published: July 2019

Three decades ago Cornalba and Harris proved a fundamental positivity result for divisor classes associated to families of stable curves. In this paper we establish an analogous positivity result for divisor classes associated to families of stable differentials.
Supporting Policy Reform from the Outside
Authors: Smets Lodewijk
Published: July 2019

Sound 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

This 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.
Can polyaryletherketone cage be used to achieve union and maintain correction in anterior calcaneal lengthening osteotomy for treatment of flexible flatfoot?
Authors: Zaghloul Khaled M. , Saied Ahmed Mostafa , Abouelnas Bassam A. , Al Adl Wael Ali M.
Published: July 2019

A structural graft is often used to maintain correction and achieve union after anterior calcaneal lengthening osteotomy for treatment of flexible flatfoot. Autograft, the current gold standard, is limited in availability and configuration and is associated with donor site morbidity in as much as 48%, whereas the alternative allograft carries risks of disease transmission and collapse. Polyaryletherketone cage, with a healing rate similar to that of autograft, high stability, and no donor-site morbidity, has been used in spine surgery. However, its use has not been documented in foot and ankle surgery. We reviewed 15 patients with painful flatfeet after failure of conservative treatment who were treated by anterior calcaneal lengthening osteotomy using polyaryletherketone cage instead of bone graft. Minimum follow-up was 1 year (average, 1.27 years; range, 1–1.5 years). The male–female ratio was 1:1.5 (six males, nine females). Mean age at time of surgery was 10.8 ± 1.7 years (range, 8–13.5 years). Minimum follow-up was 1 year (average, 1.27 years; range, 1–1.5 years). Nine patients had a unilateral procedure and three had a simultaneous bilateral procedure, for a total of 15 operated feet (seven right and eight left). The paired t-test result was statistically significant in comparison of radiographic measurements at presurgery and postsurgery with P value <0.001. All cases showed full union clinically and radiographically at last follow-ups and no complications occurred. Our data suggest that polyaryletherketone cage may be used as a structural graft option for anterior calcaneal lengthening osteotomy.
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
Development of a Novel Cervical Deformity Surgical Invasiveness Index
Authors: Passias Peter G. , Horn Samantha R. , Soroceanu Alexandra , Oh Cheongeun , Ailon Tamir , Neuman Brian J. , Lafage Virginie , Lafage Renaud , Smith Justin S. , Line Breton , Bortz Cole A. , Segreto Frank A. , Brown Avery , Alas Haddy , Pierce Katherine E. , Eastlack Robert K. , Sciubba Daniel M. , Protopsaltis Themistocles S. , Klineberg Eric O. , Burton Douglas C. , Hart Robert A. , Schwab Frank J. , Bess Shay , Shaffrey Christopher I. , Ames Christopher P.
Published: July 2019

Study Design.

Retrospective review.

Objective.

The aim of this study was to develop a novel surgical invasiveness index for cervical deformity (CD) surgery that incorporates CD-specific parameters.

Summary of Background Data.

There has been a surgical invasiveness index for general spine surgery and adult spinal deformity, but a CD index has not been developed.

Methods.

CD was defined as at least one of the following: C2-C7 Cobb >10°, cervical lordosis (CL) >10°, cervical sagittal vertical axis (cSVA) >4 cm, chin brow vertical angle >25°. Consensus from experienced spine and neurosurgeons selected weightings for each variable that went into the invasiveness index. Binary logistic regression predicted high operative time (>338 minutes), estimated blood loss (EBL) (>600 mL), or length of stay (LOS) >5 days) based on the median values of operative time, EBL, and LOS. Multivariable regression modeling was utilized to construct a final model incorporating the strongest combination of factors to predict operative time, LOS, and EBL.

Results.

Eighty-five CD patients were included (61 years, 66% females). The variables in the newly developed CD invasiveness index with their corresponding weightings were: history of previous cervical surgery (3), anterior cervical discectomy and fusion (2/level), corpectomy (4/level), levels fused (1/level), implants (1/level), posterior decompression (2/level), Smith-Peterson osteotomy (2/level), three-column osteotomy (8/level), fusion to upper cervical spine (2), absolute change in T1 slope minus cervical lordosis, cSVA, T4-T12 thoracic kyphosis (TK), and sagittal vertical axis (SVA) from baseline to 1-year. The newly developed CD-specific invasiveness index strongly predicted long LOS (R
2 = 0.310, P < 0.001), high EBL (R
2 = 0.170, P = 0.011), and extended operative time (R
2 = 0.207, P = 0.031). A second analysis used multivariable regression modeling to determine which combination of factors in the newly developed index were the strongest determinants of operative time, LOS, and EBL. The final predictive model included: number of corpectomies, levels fused, decompression, combined approach, and absolute changes in SVA, cSVA, and TK. This model predicted EBL (R
2 = 0.26), operative time (R
2 = 0.12), and LOS (R
2 = 0.13).

Conclusion.

Extended LOS, operative time, and high blood loss were strongly predicted by the newly developed CD invasiveness index, incorporating surgical factors and radiographic parameters clinically relevant for patients undergoing CD corrective surgery.

Level of Evidence: 4
Association of Susceptibility Genes for Adolescent Idiopathic Scoliosis and Intervertebral Disc Degeneration With Adult Spinal Deformity
Authors: Takeda Kazuki , Kou Ikuyo , Hosogane Naobumi , Otomo Nao , Yagi Mitsuru , Kaneko Shinjiro , Kono Hitoshi , Ishikawa Masayuki , Takahashi Yohei , Ikegami Takeshi , Nojiri Kenya , Okada Eijiro , Funao Haruki , Okuyama Kunimasa , Tsuji Takashi , Fujita Nobuyuki , Nagoshi Narihito , Tsuji Osahiko , Ogura Yoji , Ishii Ken , Nakamura Masaya , Matsumoto Morio , Ikegawa Shiro , Watanabe Kota
Published: July 2019

Study Design.

Genetic case-control study of single nucleotide polymorphisms (SNPs).

Objective.

To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD).

Summary of Background Data.

ASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined.

Methods.

ASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay.

Results.

Among the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10−4, 1.00 × 10−2, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10−2). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10−4) and with a left convex lumbar curve (P = 6.70 × 10−4), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10−2).

Conclusion.

rs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.

Level of Evidence: 4