bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children
Authors: McFarland Elizabeth J , Karron Ruth A , Muresan Petronella , Cunningham Coleen K , Libous Jennifer , Perlowski Charlotte , Thumar Bhagvanji , Gnanashanmugam Devasena , Moye Jack , Schappell Elizabeth , Barr Emily , Rexroad Vivian , Fearn Laura , Spector Stephen A , Aziz Mariam , Cielo Mikhaela , Beneri Christy , Wiznia Andrew , Luongo Cindy , Collins Peter , Buchholz Ursula J 
Published: November 2019

Abstract

Background
The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children.

Methods
Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.

Results
Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.

Conclusions
LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
Gene cloning and characterization of thiourocanate hydratase from Burkholderia sp. HME13
Authors: Muramatsu Hisashi , Miyaoku Haruna , Kurita Syuya , Matsuo Hidenori , Kashiwagi Takehiro , Kim Chul-Sa , Hayashi Motoko , Yamamoto Hiroaki , Kato Shin-Ichiro , Nagata Shinji 
Published: November 2019

AbstractA novel enzyme, thiourocanate hydratase, which catalyses the conversion of thiourocanic acid to 3-(5-oxo-2-thioxoimidazolidin-4-yl) propionic acid, was isolated from the ergothioneine-utilizing strain, Burkholderia sp. HME13. When the HME13 cells were cultured in medium containing ergothioneine as the sole nitrogen source, thiourocanate-metabolizing activity was detected in the crude extract from the cells. However, activity was not detected in the crude extract from HME13 cells that were cultured in Luria-Bertani medium. The gene encoding thiourocanate hydratase was cloned and expressed in Escherichia coli, and the recombinant enzyme was purified to homogeneity. The enzyme showed maximum activity at pH 7.5 and 55°C and was stable between pH 5.0 and 10.5, and at temperatures up to 45°C. The Km and Vmax values of thiourocanate hydratase towards thiourocanic acid were 30 μM and 7.1 μmol/min/mg, respectively. The enzyme was strongly inhibited by CuCl2 and HgCl2. The amino acid sequence of the enzyme showed 46% identity to urocanase from Pseudomonas putida, but thiourocanate hydratase had no urocanase activity.
Health and Reference Classes
Authors: Werkhoven Sander 
Published: November 2019

Abstract
In this article, I address two objections developed by Kingma against Boorse’s (1977) bio-statistical theory of health, the objections that choice of reference classes renders the theory both circular and problematically value-laden. These objections not only apply to the bio-statistical theory of health but also to other naturalistic theories, like the dispositional theory of health. I present three rejoinders. First, I argue that the circularity objection arises from excessive methodological demands. Second, I argue that naturalists can resist the normativist claim that health and pathology are differentiated on the basis of personal or cultural values. Finally, I show that it is possible to justify choices between rival theories of health without the interference of evaluative commitments. With these rejoinders, I conclude that the bio-statistical theory, as well as other naturalistic theories of health utilizing reference classes, is not undermined by Kingma’s arguments.
Whom You Don't Know, You Don't Trust: Vernacular Security, Distrust, and Its Exclusionary Effects in Post-Conflict Societies
Authors: Benzing Bettina 
Published: November 2019

AbstractArguments about the importance of vernacular security focus on its positive and inclusive potential for peacebuilding. Reflecting on the special constitutional and sociopolitical challenges post-conflict societies face in the aftermath of conflict, though, this article focuses on the way perceptions of security and security in the vernacular can exacerbate exclusionary effects in post-conflict societies. I discuss current approaches to security concepts dealing with social perceptions of (in)security and the linkages made in research between vernacular security and local peace. But I also highlight exclusionary structures in post-conflict settings, which are most often marked by distrustful social relations, as a byproduct of security measures. I argue, in contrast to current assumptions in research on security in the vernacular, that everyday measures not only have positive implications for peacebuilding but can also lead to social exclusion, fostering violence and hindering social equality, development, and peace.
Citrus PH4–Noemi regulatory complex is involved in proanthocyanidin biosynthesis via a positive feedback loop
Authors: Zhang Yin , Ye Junli , Liu Chaoyang , Xu Qiang , Long Lichang , Deng Xiuxin 
Published: November 2019

Abstract
Proanthocyanidins (PAs; or condensed tannins) are a major class of flavonoids that contribute to citrus fruit quality. However, the molecular mechanism responsible for PA biosynthesis and accumulation in citrus remains unclear. Here, we identify a PH4–Noemi regulatory complex that regulates proanthocyanidin biosynthesis in citrus. Overexpression of PH4 or Noemi in citrus calli activated the expression of PA biosynthetic genes and significantly increased the PA content. Interestingly, Noemi was also shown to be up-regulated in CsPH4-overexpressing lines compared with wild-type calli. Simultaneously, CsPH4 partially complemented the PA-deficient phenotype of the Arabidopsis tt2 mutant and promoted PA accumulation in the wild-type. Further analysis revealed that CsPH4 interacted with Noemi, and together these proteins synergistically activated the expression of PA biosynthetic genes by directly binding to the MYB-recognizing elements (MRE) of the promoters of these genes. Moreover, CsPH4 could directly bind to the promoter of Noemi and up-regulate the expression of this gene. These findings explain how the CsPH4–Noemi regulatory complex contributes to the activation of PA biosynthetic genes via a positive feedback loop and provide new insights into the molecular mechanisms underlying PA biosynthesis, which can be effectively employed for metabolic engineering to improve citrus fruit quality.
Seed comparative genomics in three coffee species identify desiccation tolerance mechanisms in intermediate seeds
Authors: Stavrinides Anna K , Dussert Stéphane , Combes Marie-Christine , Fock-Bastide Isabelle , Severac Dany , Minier Jérôme , Bastos-Siqueira Aldecinei , Demolombe Vincent , Hem Sonia , Lashermes Philippe , Joët Thierry 
Published: November 2019

Abstract
In contrast to desiccation-tolerant ‘orthodox’ seeds, so-called ‘intermediate’ seeds cannot survive complete drying and are short-lived. All species of the genus Coffea produce intermediate seeds, but they show a considerable variability in seed desiccation tolerance (DT), which may help to decipher the molecular basis of seed DT in plants. We performed a comparative transcriptome analysis of developing seeds in three coffee species with contrasting desiccation tolerance. Seeds of all species shared a major transcriptional switch during late maturation that governs a general slow-down of metabolism. However, numerous key stress-related genes, including those coding for the late embryogenesis abundant protein EM6 and the osmosensitive calcium channel ERD4, were up-regulated during DT acquisition in the two species with high seed DT, C. arabica and C. eugenioides. By contrast, we detected up-regulation of numerous genes involved in the metabolism, transport, and perception of auxin in C. canephora seeds with low DT. Moreover, species with high DT showed a stronger down-regulation of the mitochondrial machinery dedicated to the tricarboxylic acid cycle and oxidative phosphorylation. Accordingly, respiration measurements during seed dehydration demonstrated that intermediate seeds with the highest DT are better prepared to cease respiration and avoid oxidative stresses.
Combating stress: the interplay between hormone signaling and autophagy in plants
Authors: Liao Ching-Yi , Bassham Diane C 
Published: November 2019

AbstractAutophagy is a conserved recycling process in which cellular components are delivered to and degraded in the vacuole/lysosome for reuse. In plants, it assists in responding to dynamic environmental conditions and maintaining metabolite homeostasis under normal or stress conditions. Under stress, autophagy is activated to remove damaged components and to recycle nutrients for survival, and the energy sensor kinases target of rapamycin (TOR) and SNF-related kinase 1 (SnRK1) are key to this activation. Here, we discuss accumulating evidence that hormone signaling plays critical roles in regulating autophagy and plant stress responses, although the molecular mechanisms by which this occurs are often not clear. Several hormones have been shown to regulate TOR activity during stress, in turn controlling autophagy. Hormone signaling can also regulate autophagy gene expression, while, reciprocally, autophagy can regulate hormone synthesis and signaling pathways. We highlight how the interplay between major energy sensors, plant hormones, and autophagy under abiotic and biotic stress conditions can assist in plant stress tolerance.
The buildup of strongly barred galaxies in the TNG100 simulation
Authors: Rosas-Guevara Yetli , Bonoli Silvia , Dotti Massimo , Zana Tommaso , Nelson Dylan , Pillepich Annalisa , Ho Luis C , Izquierdo-Villalba David , Hernquist Lars , Pakmor Rüediger 
Published: November 2019

Abstract
We analyse the properties of strongly barred disc galaxies using the TNG100 simulation, a cosmological hydrodynamical realisation of the IllustrisTNG suite. We identify 270 disc galaxies at z = 0 in the stellar mass range $M_{*}=10^{10.4-11}\rm M_{\odot}$, of which 40 per cent are barred. Of the detected bars, more than half are strong. We find that the fraction of barred galaxies increases with stellar mass, in agreement with observational results. Strongly barred galaxies exhibit, overall, lower gas-to-stellar mass ratios compared to unbarred galaxies. The majority of barred galaxies are quenched (sSFR ∼10−11.7yr−1), whereas unbarred galaxies continue to be active (sSFR ∼10−10.3yr−1) on the main sequence of star-forming galaxies. We explore the evolution of strongly barred and unbarred galaxies to investigate their formation and quenching histories. We find that strong bars form between 0.5 < z < 1.5, with more massive galaxies hosting older bars. Strong bars form in galaxies with an early-established prominent disc component, undergoing periods of enhanced star formation and black hole accretion, possibly assisted by cosmological inflows. Unbarred galaxies, on the other hand, assemble most of their mass and disc component at late times. The nuclear region of strongly barred galaxies quenches shortly after bar formation, while unbarred galaxies remain active across time. Our findings are indicative of bar quenching, possibly assisted by nuclear feedback processes. We conclude that the cosmological environment, together with small scale feedback processes, determine the chances of a galaxy to form a bar and to rapidly quench its central region.
DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts
Authors: Karagkouni Dimitra , Paraskevopoulou Maria D , Tastsoglou Spyros , Skoufos Giorgos , Karavangeli Anna , Pierros Vasilis , Zacharopoulou Elissavet , Hatzigeorgiou Artemis G 
Published: November 2019

Abstract
DIANA-LncBase v3.0 (www.microrna.gr/LncBase) is a reference repository with experimentally supported miRNA targets on non-coding transcripts. Its third version provides approximately half a million entries, corresponding to ∼240 000 unique tissue and cell type specific miRNA–lncRNA pairs. This compilation of interactions is derived from the manual curation of publications and the analysis of >300 high-throughput datasets. miRNA targets are supported by 14 experimental methodologies, applied to 243 distinct cell types and tissues in human and mouse. The largest part of the database is highly confident, AGO-CLIP-derived miRNA-binding events. LncBase v3.0 is the first relevant database to employ a robust CLIP-Seq-guided algorithm, microCLIP framework, to analyze 236 AGO-CLIP-Seq libraries and catalogue ∼370 000 miRNA binding events. The database was redesigned from the ground up, providing new functionalities. Known short variant information, on >67,000 experimentally supported target sites and lncRNA expression profiles in different cellular compartments are catered to users. Interactive visualization plots, portraying correlations of miRNA–lncRNA pairs, as well as lncRNA expression profiles in a wide range of cell types and tissues, are presented for the first time through a dedicated page. LncBase v3.0 constitutes a valuable asset for ncRNA research, providing new insights to the understanding of the still widely unexplored lncRNA functions.
Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases
Authors: Zheng Li , Meng Yuan , Campbell Judith L , Shen Binghui 
Published: November 2019

AbstractDNA2 nuclease/helicase is a structure-specific nuclease, 5′-to-3′ helicase, and DNA-dependent ATPase. It is involved in multiple DNA metabolic pathways, including Okazaki fragment maturation, replication of ‘difficult-to-replicate’ DNA regions, end resection, stalled replication fork processing, and mitochondrial genome maintenance. The participation of DNA2 in these different pathways is regulated by its interactions with distinct groups of DNA replication and repair proteins and by post-translational modifications. These regulatory mechanisms induce its recruitment to specific DNA replication or repair complexes, such as DNA replication and end resection machinery, and stimulate its efficient cleavage of various structures, for example, to remove RNA primers or to produce 3′ overhangs at telomeres or double-strand breaks. Through these versatile activities at replication forks and DNA damage sites, DNA2 functions as both a tumor suppressor and promoter. In normal cells, it suppresses tumorigenesis by maintaining the genomic integrity. Thus, DNA2 mutations or functional deficiency may lead to cancer initiation. However, DNA2 may also function as a tumor promoter, supporting cancer cell survival by counteracting replication stress. Therefore, it may serve as an ideal target to sensitize advanced DNA2-overexpressing cancers to current chemo- and radiotherapy regimens.
Expanding the editable genome and CRISPR–Cas9 versatility using DNA cutting-free gene targeting based on in trans paired nicking
Authors: Chen Xiaoyu , Tasca Francesca , Wang Qian , Liu Jin , Janssen Josephine M , Brescia Marcella D , Bellin Milena , Szuhai Karoly , Kenrick Josefin , Frock Richard L , Gonçalves Manuel A F V 
Published: November 2019

AbstractGenome editing typically involves recombination between donor nucleic acids and acceptor genomic sequences subjected to double-stranded DNA breaks (DSBs) made by programmable nucleases (e.g. CRISPR–Cas9). Yet, nucleases yield off-target mutations and, most pervasively, unpredictable target allele disruptions. Remarkably, to date, the untoward phenotypic consequences of disrupting allelic and non-allelic (e.g. pseudogene) sequences have received scant scrutiny and, crucially, remain to be addressed. Here, we demonstrate that gene-edited cells can lose fitness as a result of DSBs at allelic and non-allelic target sites and report that simultaneous single-stranded DNA break formation at donor and acceptor DNA by CRISPR–Cas9 nickases (in trans paired nicking) mostly overcomes such disruptive genotype-phenotype associations. Moreover, in trans paired nicking gene editing can efficiently and precisely add large DNA segments into essential and multiple-copy genomic sites. As shown herein by genotyping assays and high-throughput genome-wide sequencing of DNA translocations, this is achieved while circumventing most allelic and non-allelic mutations and chromosomal rearrangements characteristic of nuclease-dependent procedures. Our work demonstrates that in trans paired nicking retains target protein dosages in gene-edited cell populations and expands gene editing to chromosomal tracts previously not possible to modify seamlessly due to their recurrence in the genome or essentiality for cell function.
pathDIP 4: an extended pathway annotations and enrichment analysis resource for human, model organisms and domesticated species
Authors: Rahmati Sara , Abovsky Mark , Pastrello Chiara , Kotlyar Max , Lu Richard , Cumbaa Christian A , Rahman Proton , Chandran Vinod , Jurisica Igor 
Published: November 2019

Abstract
PathDIP was introduced to increase proteome coverage of literature-curated human pathway databases. PathDIP 4 now integrates 24 major databases. To further reduce the number of proteins with no curated pathway annotation, pathDIP integrates pathways with physical protein–protein interactions (PPIs) to predict significant physical associations between proteins and curated pathways. For human, it provides pathway annotations for 5366 pathway orphans. Integrated pathway annotation now includes six model organisms and ten domesticated animals. A total of 6401 core and ortholog pathways have been curated from the literature or by annotating orthologs of human proteins in the literature-curated pathways. Extended pathways are the result of combining these pathways with protein-pathway associations that are predicted using organism-specific PPIs. Extended pathways expand proteome coverage from 81 088 to 120 621 proteins, making pathDIP 4 the largest publicly available pathway database for these organisms and providing a necessary platform for comprehensive pathway-enrichment analysis. PathDIP 4 users can customize their search and analysis by selecting organism, identifier and subset of pathways. Enrichment results and detailed annotations for input list can be obtained in different formats and views. To support automated bioinformatics workflows, Java, R and Python APIs are available for batch pathway annotation and enrichment analysis. PathDIP 4 is publicly available at http://ophid.utoronto.ca/pathDIP.
CDD/SPARCLE: the conserved domain database in 2020
Authors: Lu Shennan , Wang Jiyao , Chitsaz Farideh , Derbyshire Myra K , Geer Renata C , Gonzales Noreen R , Gwadz Marc , Hurwitz David I , Marchler Gabriele H , Song James S , Thanki Narmada , Yamashita Roxanne A , Yang Mingzhang , Zhang Dachuan , Zheng Chanjuan , Lanczycki Christopher J , Marchler-Bauer Aron 
Published: November 2019

Abstract
As NLM’s Conserved Domain Database (CDD) enters its 20th year of operations as a publicly available resource, CDD curation staff continues to develop hierarchical classifications of widely distributed protein domain families, and to record conserved sites associated with molecular function, so that they can be mapped onto user queries in support of hypothesis-driven biomolecular research. CDD offers both an archive of pre-computed domain annotations as well as live search services for both single protein or nucleotide queries and larger sets of protein query sequences. CDD staff has continued to characterize protein families via conserved domain architectures and has built up a significant corpus of curated domain architectures in support of naming bacterial proteins in RefSeq. These architecture definitions are available via SPARCLE, the Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.
Opportunistic infections after conversion to belatacept in kidney transplantation
Authors: Bertrand Dominique , Chavarot Nathalie , Gatault Philippe , Garrouste Cyril , Bouvier Nicolas , Grall-Jezequel Anne , Jaureguy Maïté , Caillard Sophie , Lemoine Mathilde , Colosio Charlotte , Golbin Léonard , Rerolle Jean-Philippe , Thierry Antoine , Sayegh Johnny , Etienne Isabelle , Lebourg Ludivine , Sberro Rebecca , Guerrot Dominique 
Published: November 2019

Abstract

Background
Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported.

Methods
We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients.

Results
Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein–Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate &lt;25/mL/min/1.73 m2 on the day of the switch and the use of immunosuppressive agents before transplantation were associated with the occurrence of OPI. We found a higher rate of infection-related hospitalization (24.1 versus 12.3/100 person-years, P = 0.0007) and also a higher rate of OPI (13.2 versus 6.7/100 person-years, P = 0.005) in the early conversion group (within 6 months).

Conclusions
The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case–control study.