bluuebunny/crossref_metadata_2025 huggingface dataset:
Congestion in highways when tolls and railroads matter: evidence from European cities
Authors: Garcia-López Miquel-Àngel , Pasidis Ilias , Viladecans-Marsal Elisabet
Published: June 2021

Using data from the 545 largest European cities, we study whether the expansion of their highway capacity provides a solution to the problem of traffic congestion. Our results confirm that in the long run, and in line with the ‘fundamental law of highway congestion’, the expansion in cities of lane kilometres causes an increase in vehicle traffic that does not solve urban congestion. We disentangle the increase in traffic due to the increases in coverage and in capacity. We further introduce road pricing and public transit policies in order to test whether they moderate congestion. Our findings confirm that the induced demand is considerably smaller in cities with road pricing schemes, and that congestion decreases with the expansion of public transportation.
Genetic Background of the Polish Primitive Horse (Konik) Coat Color Variation—New Insight into Dun Dilution Phenotypic Effect
Authors: Cieslak Jakub , Brooks Samantha Ann , Wodas Lukasz , Mantaj Weronika , Borowska Alicja , Sliwowska Joanna Helena , Ziarniak Kamil , Mackowski Mariusz
Published: June 2021

Only the blue dun coat color, produced by the action of the dun allele on the background of a black base coat, is officially permitted in the Polish primitive horse (PPH, Konik) breed, yet the population is not visually homogenous and various coat color shades occur. Herein, the molecular background of PPH coat color was studied based on genotyping of known causative variants in equine coat color-related genes (ASIP, MC1R, TBX3, SLC36A1, SLC45A2, PMEL17, and RALY). Additionally, screening for the new polymorphisms was conducted for the ASIP gene coding sequence and the TBX3 1.6-kb insert (associated with the dun dilution). We did not observe the champagne, silver, or cream color dilution variants in the PPH breed. A significant association (P < 0.01) was recorded for the genotype in TBX3 gene 1.6 kb in/del and the degree of dun coat dilution, demonstrating that the dominant action of the dun mutation is not fully penetrant. In addition to the effect of the 1.6 kb in/del zygosity, variants within the TBX3 insert were significantly associated with PPH coat color variability (P < 0.01), suggesting the presence of an additional allele at this locus. Finally, we identified a high frequency (35%) of genetically bay dun-colored PPH individuals that are officially recorded as blue (black base coat) duns. We propose that the difficulty in distinguishing these 2 phenotypes visually is due to an independent locus upstream of the ASIP gene, which was recently described as darkening the typical bay pigmentation shade.
Faster, reduced cost calibration method development methods for the analysis of fermentation product using near-infrared spectroscopy (NIRS)
Authors: Agbonkonkon Nosa , Wojciechowski Greg , Abbott Derek A , Gaucher Sara P , Yim Daniel R , Thompson Andrew W , Leavell Michael D
Published: June 2021

Recent innovations in synthetic biology, fermentation, and process development have decreased time to market by reducing strain construction cycle time and effort. Faster analytical methods are required to keep pace with these innovations, but current methods of measuring fermentation titers often involve manual intervention and are slow, time-consuming, and difficult to scale. Spectroscopic methods like near-infrared (NIR) spectroscopy address this shortcoming; however, NIR methods require calibration model development that is often costly and time-consuming. Here, we introduce two approaches that speed up calibration model development. First, generalized calibration modeling (GCM) or sibling modeling, which reduces calibration modeling time and cost by up to 50% by reducing the number of samples required. Instead of constructing analyte-specific models, GCM combines a reduced number of spectra from several individual analytes to produce a large pool of spectra for a generalized model predicting all analyte levels. Second, randomized multicomponent multivariate modeling (RMMM) reduces modeling time by mixing multiple analytes into one sample matrix and then taking the spectral measurements. Afterward, individual calibration methods are developed for the various components in the mixture. Time saved from the use of RMMM is proportional to the number of components or analytes in the mixture. When combined, the two methods effectively reduce the associated cost and time for calibration model development by a factor of 10.
Effect of Vegetation on the Abundance of Tick Vectors in the Northeastern United States: A Review of the Literature
Authors: Mathisson Daniel C , Kross Sara M , Palmer Matthew I , Diuk-Wasser Maria A
Published: June 2021

Tick-borne illnesses have been on the rise in the United States, with reported cases up sharply in the past two decades. In this literature review, we synthesize the available research on the relationship between vegetation and tick abundance for four tick species in the northeastern United States that are of potential medical importance to humans. The blacklegged tick (Ixodes scapularis) (Say; Acari: Ixodidae) is found to be positively associated with closed canopy forests and dense vegetation thickets, and negatively associated with open canopy environments, such as grasslands or old agricultural fields. The American dog tick (Dermacentor variabilis) (Say; Acari: Ixodidae) has little habitat overlap with I. scapularis, with abundance highest in grasses and open-canopy fields. The lone star tick (Amblyomma americanum) (Linnaeus; Acari: Ixodidae) is a habitat generalist without consistent associations with particular types of vegetation. The habitat associations of the recently introduced Asian longhorned tick (Haemaphysalis longicornis) (Neumann; Acari: Ixodidae) in the northeastern United States, and in other regions where it has invaded, are still unknown, although based on studies in its native range, it is likely to be found in grasslands and open-canopy habitats.
Parenting Practices, Bedtime Routines, and Consistency: Associations with Pediatric Sleep Problems
Authors: Shetty Janavi , Newton Adam T , Reid Graham J
Published: June 2021

Objectives

Investigate the direct and moderating effects of daytime parenting practices on the relationship between bedtime routines and pediatric sleep problems.

Methods

A community sample of 407 parents with children 2–10 years old completed measures of parenting practices (i.e., laxness and over-reactivity) and bedtime routines (i.e., consistency and reactivity to changes in routines). Sleep problems (i.e., severity and signaled night waking) were assessed by a parent-report questionnaire and sleep diaries.

Results

Higher parenting laxness (β = .13) and less bedtime routine consistency (β = −.34) significantly predicted sleep problem severity. Laxness moderated the relationship between bedtime reactivity and sleep problem severity: when bedtime reactivity was high, higher parental laxness was associated with more severe sleep problems.

Conclusions

Daytime parenting practices are important to consider when children are reactive to changes in bedtime routines, as permissive or inconsistent daytime parenting practices were found to be associated with more severe sleep problems. Future research should examine the effects of parenting practices and bedtime routines on problematic signaled night waking in a clinical sample of children.
O2-(2,4-dinitrophenyl) diazeniumdiolate derivative induces G2/M arrest via PTEN-mediated inhibition of PI3K/Akt pathway in hepatocellular carcinoma cells
Authors: Liu Ling , Xu Jinglei , Zhai Ziyu , Cao Mengyao , Huang Zile , Xing Yihao , Chen Jingjing
Published: June 2021

Objectives

The study aimed to investigate whether G2/M arrest caused by O2-(2,4-dinitrophenyl) diazeniumdiolate derivative (JS-K) was related to PTEN-mediated inhibition of PI3K/Akt pathway in hepatocellular carcinoma cells.

Methods

The cell apoptosis was detected by DAPI staining and Annexin V-FITC/PI dual staining. The cell cycle was analysed by PI staining. The expressions of cell cycle-related proteins, PTEN and PI3K/AKT pathway were measured by Western blot. The rat model of primary hepatic carcinoma was established with diethylnitrosamine to verify the antitumour effects of JS-K.

Key findings

The morphological features of apoptosis were obviously reversed when the cells were pre-treated with bpv(pic), followed by treatment with JS-K. JS-K mediated G2/M arrest and down-regulated expressions of cyclin B1. Meanwhile, it up-regulated the expression of p-Cdk1, p-Chk2 and p-CDC25C while down-regulated that of Cdk1 and CDC25C. Furthermore, JS-K also enhanced the expressions of p21 and p27, PTEN and p53 while decreased the expressions of p-PTEN, PI3K and p-AKT. However, bpv(pic) and Carboxy-PTIO could reverse JS-K-induced G2/M cell arrest and PTEN-mediated inhibition of the PI3K/AKT pathway. The same results were also testified in the rat model of primary hepatic carcinoma.

Conclusions

JS-K caused G2/M arrest through PTEN-mediated inhibition of the PI3K/AKT pathway involving Chk2/CDC25C/Cdk1 checkpoint.
The plant nuclear lamina proteins NMCP1 and NMCP2 form a filamentous network with lateral filament associations
Authors: Masuda Kiyoshi , Hikida Riku , Fujino Kaien
Published: June 2021

Plant genomes lack genes encoding intermediate filament proteins, including lamins; however, functional lamin analogues are presumed to exist in plants. Plant-specific coiled-coil proteins, that is, nuclear matrix constituent proteins (NMCPs), are the most likely candidates as the structural elements of the nuclear lamina because they exhibit a lamin-like domain arrangement. They are exclusively localized at the nuclear periphery and have functions that are analogous to those of lamins. However, their assembly into filamentous polymers has not yet been confirmed. In this study, we examined the higher-order structure of NMCP1 and NMCP2 in Apium graveolens cells by using stimulated emission depletion microscopy combined with immunofluorescence cell labelling. Our analyses revealed that NMCP1 and NMCP2 form intricate filamentous networks, which include thick segments consisting of filament bundles, forming a dense filamentous layer extending across the nuclear periphery. Furthermore, the outermost chromatin distribution was found to be in the nucleoplasm-facing region of the nuclear lamina. Recombinant Daucus carota NMCP1 with a His-tag produced in Escherichia coli refolded into dimers and self-assembled into filaments and filament bundles. These results suggest that NMCP1 and NMCP2 organize into the nuclear lamina by forming a filamentous network with filament bundles that localize at the nuclear periphery.
Double-faced role of Bcl-2-associated athanogene 7 in plant–Phytophthora interaction
Authors: Zhou Yang , Yang Kun , Cheng Ming , Cheng Yang , Li Yurong , Ai Gan , Bai Tian , Xu Ruofei , Duan Weiwei , Peng Hao , Li Xiaobo , Xia Ai , Wang Yuanchao , Jing Maofeng , Dou Daolong , Dickman Marty B
Published: June 2021

Due to their sessile nature, plants must respond to various environmental assaults in a coordinated manner. The endoplasmic reticulum is a central hub for plant responses to various stresses. We previously showed that Phytophthora utilizes effector PsAvh262-mediated binding immunoglobulin protein (BiP) accumulation for suppressing endoplasmic reticulum stress-triggered cell death. As a BiP binding partner, Bcl-2-associated athanogene 7 (BAG7) plays a crucial role in the maintenance of the unfolded protein response, but little is known about its role in plant immunity. In this work, we reveal a double-faced role of BAG7 in Arabidopsis–Phytophthora interaction in which it regulates endoplasmic reticulum stress-mediated immunity oppositely in different cellular compartments. In detail, it acts as a susceptibility factor in the endoplasmic reticulum, but plays a resistance role in the nucleus against Phytophthora. Phytophthora infection triggers the endoplasmic reticulum-to-nucleus translocation of BAG7, the same as abiotic heat stress; however, this process can be prevented by PsAvh262-mediated BiP accumulation. Moreover, the immunoglobulin/albumin-binding domain in PsAvh262 is essential for both pathogen virulence and BiP accumulation. Taken together, our study uncovers a double-faced role of BAG7; Phytophthora advances its colonization in planta by utilizing an effector to detain BAG7 in the endoplasmic reticulum.
Natural variations in the P-type ATPase heavy metal transporter gene ZmHMA3 control cadmium accumulation in maize grains
Authors: Tang Bin , Luo Meijie , Zhang Yunxia , Guo Huanle , Li Jingna , Song Wei , Zhang Ruyang , Feng Zhen , Kong Mengsi , Li Han , Cao Zhongyang , Lu Xiaoduo , Li Delin , Zhang Jianhua , Wang Ronghuan , Wang Yuandong , Chen Zhihui , Zhao Yanxin , Zhao Jiuran
Published: June 2021

Cadmium (Cd) accumulation in maize grains is detrimental to human health. Developing maize varieties with low Cd content is important for safe consumption of maize grains. However, the key genes controlling maize grain Cd accumulation have not been cloned. Here, we identified one major locus for maize grain Cd accumulation (qCd1) using a genome-wide association study (GWAS) and bulked segregant RNA-seq analysis with a biparental segregating population of Jing724 (low-Cd line) and Mo17 (high-Cd line). The candidate gene ZmHMA3 was identified by fine mapping and encodes a tonoplast-localized heavy metal P-type ATPase transporter. An ethyl methane sulfonate mutant analysis and an allelism test confirmed that ZmHMA3 influences maize grain Cd accumulation. A transposon in intron 1 of ZmHMA3 is responsible for the abnormal amino acid sequence in Mo17. Based on the natural sequence variations in the ZmHMA3 gene of diverse maize lines, four PCR-based molecular markers were developed, and these were successfully used to distinguish five haplotypes with different grain Cd contents in the GWAS panel and to predict grain Cd contents of widely used maize inbred lines and hybrids. These molecular markers can be used to breed elite maize varieties with low grain Cd contents.
The impact of the CMB on the evolution of high-z blazars
Authors: Ighina L , Caccianiga A , Moretti A , Belladitta S , Della Ceca R , Diana A
Published: June 2021

Different works have recently found an increase of the average X-ray-to-radio luminosity ratio with redshift in the blazar population. We evaluate here whether the inverse Compton interaction between the relativistic electrons within the jet and the photons of the cosmic microwave background (IC/CMB) can explain this trend. Moreover, we test whether the IC/CMB model can also be at the origin of the different space density evolutions found in X-ray and radio-selected blazar samples. By considering the best statistically complete samples of blazars selected in the radio or in the X-ray band and covering a large range of redshift (0.5 ≲ z ≲ 5.5), we evaluate the expected impact of the CMB on the observed X-ray emission on each sample and then we compare these predictions with the observations. We find that this model can satisfactorily explain both the observed trend of the X-ray-to-radio luminosity ratios with redshift and the different cosmological evolutions derived from the radio and X-ray band. Finally, we discuss how currently on-going X-ray missions, like extended ROentgen Survey with an Imaging Telescope Array, could help to further constrain the observed evolution at even higher redshifts (up to z ∼ 6–7).
Trichostatin A mitigates radiation-induced teratogenesis in C57Bl/6 mice
Authors: Haritwal Teena , Goyal Nikita , Gupta Noopur , Parvez Suhel , Agrawala Paban K
Published: June 2021

Radiation exposure in utero is known to lead to serious concerns to both the mother and children, including developmental anomalies in the children. In the recent past, trichostatin A, an HDAC (histone deacetylase) inhibitor and epigenetic modifier, has been shown to mitigate radiation-induced anomalies in the male reproductive system of C57BL/6 mice. Therefore, the current study was undertaken to evaluate the mitigating effects of trichostatin A (TSA) against radiation-induced developmental anomalies in mice. Foetuses of in utero whole-body gamma-irradiated mice during the active organogenesis period were examined for developmental anomalies at 8.5 and 18.5 days of gestation. In utero radiation exposure caused developmental anomalies like microcephaly, microphthalmia, gastroschisis and kinky tail besides prenatal mortality. TSA administration post-irradiation was observed to reduce 50% of prenatal mortality at E18.5 by reducing congenital and developmental anomalies. Observation of such results could be corroborated with the HDAC inhibitory potential of TSA knowing that developmental anomalies may have epigenetic origin. TSA, therefore, can be considered as a potential radiomitigator.
G-quadruplex-forming aptamer enhances the peroxidase activity of myoglobin against luminol
Authors: Tsukakoshi Kaori , Yamagishi Yasuko , Kanazashi Mana , Nakama Kenta , Oshikawa Daiki , Savory Nasa , Matsugami Akimasa , Hayashi Fumiaki , Lee Jinhee , Saito Taiki , Sode Koji , Khunathai Kanjana , Kuno Hitoshi , Ikebukuro Kazunori
Published: June 2021

Aptamers can control the biological functions of enzymes, thereby facilitating the development of novel biosensors. While aptamers that inhibit catalytic reactions of enzymes were found and used as signal transducers to sense target molecules in biosensors, no aptamers that amplify enzymatic activity have been identified. In this study, we report G-quadruplex (G4)-forming DNA aptamers that upregulate the peroxidase activity in myoglobin specifically for luminol. Using in vitro selection, one G4-forming aptamer that enhanced chemiluminescence from luminol by myoglobin's peroxidase activity was discovered. Through our strategy—in silico maturation, which is a genetic algorithm-aided sequence manipulation method, the enhancing activity of the aptamer was improved by introducing mutations to the aptamer sequences. The best aptamer conserved the parallel G4 property with over 300-times higher luminol chemiluminescence from peroxidase activity more than myoglobin alone at an optimal pH of 5.0. Furthermore, using hemin and hemin-binding aptamers, we demonstrated that the binding property of the G4 aptamers to heme in myoglobin might be necessary to exert the enhancing effect. Structure determination for one of the aptamers revealed a parallel-type G4 structure with propeller-like loops, which might be useful for a rational design of aptasensors utilizing the G4 aptamer-myoglobin pair.
LEO1 is a partner for Cockayne syndrome protein B (CSB) in response to transcription-blocking DNA damage
Authors: Tiwari Vinod , Kulikowicz Tomasz , Wilson David M , Bohr Vilhelm A
Published: June 2021

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as an interacting protein partner of full-length and C-terminal (Pro1010-Cys1493) CSB in two independent screens. LEO1 is a member of the RNA polymerase associated factor 1 complex (PAF1C) with roles in transcription elongation and chromatin modification. Supportive of the Y2H results, purified, recombinant LEO1 and CSB directly interact in vitro, and the two proteins exist in a common complex within human cells. In addition, fluorescently tagged LEO1 and CSB are both recruited to localized DNA damage sites in human cells. Cell fractionation experiments revealed a transcription-dependent, coordinated association of LEO1 and CSB to chromatin following either UVC irradiation or cisplatin treatment of HEK293T cells, whereas the response to menadione was distinct, suggesting that this collaboration occurs mainly in the context of bulky transcription-blocking lesions. Consistent with a coordinated interaction in DNA repair, LEO1 knockdown or knockout resulted in reduced CSB recruitment to chromatin, increased sensitivity to UVC light and cisplatin damage, and reduced RNA synthesis recovery and slower excision of cyclobutane pyrimidine dimers following UVC irradiation; the absence of CSB resulted in diminished LEO1 recruitment. Our data indicate a reciprocal communication between CSB and LEO1 in the context of transcription-associated DNA repair and RNA transcription recovery.
In-depth assessment of the PAM compatibility and editing activities of Cas9 variants
Authors: Zhang Weiwei , Yin Jianhang , Zhang-Ding Zhengrong , Xin Changchang , Liu Mengzhu , Wang Yuhong , Ai Chen , Hu Jiazhi
Published: June 2021

A series of Cas9 variants have been developed to improve the editing fidelity or targeting range of CRISPR–Cas9. Here, we employ a high-throughput sequencing approach primer-extension-mediated sequencing to analyze the editing efficiency, specificity and protospacer adjacent motif (PAM) compatibility of a dozen of SpCas9 variants at multiple target sites in depth, and our findings validate the high fidelity or broad editing range of these SpCas9 variants. With regard to the PAM-flexible SpCas9 variants, we detect significantly increased levels of off-target activity and propose a trade-off between targeting range and editing specificity for them, especially for the near-PAM-less SpRY. Moreover, we use a deep learning model to verify the consistency and predictability of SpRY off-target sites. Furthermore, we combine high-fidelity SpCas9 variants with SpRY to generate three new SpCas9 variants with both high fidelity and broad editing range. Finally, we also find that the existing SpCas9 variants are not effective in suppressing genome instability elicited by CRISPR–Cas9 editing, raising an urgent issue to be addressed.
Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer
Authors: Gupta Kushol , Wen Ying , Ninan Nisha S , Raimer Amanda C , Sharp Robert , Spring Ashlyn M , Sarachan Kathryn L , Johnson Meghan C , Van Duyne Gregory D , Matera A Gregory
Published: June 2021

Protein oligomerization is one mechanism by which homogenous solutions can separate into distinct liquid phases, enabling assembly of membraneless organelles. Survival Motor Neuron (SMN) is the eponymous component of a large macromolecular complex that chaperones biogenesis of eukaryotic ribonucleoproteins and localizes to distinct membraneless organelles in both the nucleus and cytoplasm. SMN forms the oligomeric core of this complex, and missense mutations within its YG box domain are known to cause Spinal Muscular Atrophy (SMA). The SMN YG box utilizes a unique variant of the glycine zipper motif to form dimers, but the mechanism of higher-order oligomerization remains unknown. Here, we use a combination of molecular genetic, phylogenetic, biophysical, biochemical and computational approaches to show that formation of higher-order SMN oligomers depends on a set of YG box residues that are not involved in dimerization. Mutation of key residues within this new structural motif restricts assembly of SMN to dimers and causes locomotor dysfunction and viability defects in animal models.
Cytosine base modifications regulate DNA duplex stability and metabolism
Authors: Rausch Cathia , Zhang Peng , Casas-Delucchi Corella S , Daiß Julia L , Engel Christoph , Coster Gideon , Hastert Florian D , Weber Patrick , Cardoso M Cristina
Published: June 2021

DNA base modifications diversify the genome and are essential players in development. Yet, their influence on DNA physical properties and the ensuing effects on genome metabolism are poorly understood. Here, we focus on the interplay of cytosine modifications and DNA processes. We show by a combination of in vitro reactions with well-defined protein compositions and conditions, and in vivo experiments within the complex networks of the cell that cytosine methylation stabilizes the DNA helix, increasing its melting temperature and reducing DNA helicase and RNA/DNA polymerase speed. Oxidation of methylated cytosine, however, reverts the duplex stabilizing and genome metabolic effects to the level of unmodified cytosine. We detect this effect with DNA replication and transcription proteins originating from different species, ranging from prokaryotic and viral to the eukaryotic yeast and mammalian proteins. Accordingly, lack of cytosine methylation increases replication fork speed by enhancing DNA helicase unwinding speed in cells. We further validate that this cannot simply be explained by altered global DNA decondensation, changes in histone marks or chromatin structure and accessibility. We propose that the variegated deposition of cytosine modifications along the genome regulates DNA helix stability, thereby providing an elementary mechanism for local fine-tuning of DNA metabolism.
Arabidopsis ADF1 is Regulated by MYB73 and is Involved in Response to Salt Stress Affecting Actin Filament Organization
Authors: Wang Lu , Qiu Tianqi , Yue Jianru , Guo Nannan , He Yunjian , Han Xueping , Wang Qiuyang , Jia Pengfei , Wang Hongdan , Li Muzi , Wang Che , Wang Xianling
Published: June 2021

Actin cytoskeleton and transcription factors play key roles in plant response to salt stress; however, little is known about the link between the two regulators in response to salt stress. Actin-depolymerizing factors (ADFs) are conserved actin-binding proteins in eukaryotes. Here, we revealed that the expression level of ADF1 was induced by salt stress. The adf1 mutants showed significantly reduced survival rate, increased percentage of actin cable and reduced density of actin filaments, while ADF1 overexpression seedlings displayed the opposite results when compared with WT under the same condition. Furthermore, biochemical assays revealed that MYB73, a R2R3 MYB transcription factor, binds to the promoter of ADF1 and represses its expression via the MYB-binding site core motif ACCTAC. Taken together, our results indicate that ADF1 participates in salt stress by regulating actin organization and may also serve as a potential downstream target of MYB73, which is a negative regulator of salt stress.
Maize ATR safeguards genome stability during kernel development to prevent early endosperm endocycle onset and cell death
Authors: Pedroza-Garcia Jose Antonio , Eekhout Thomas , Achon Ignacio , Nisa Maher-Un , Coussens Griet , Vercauteren Ilse , Van den Daele Hilde , Pauwels Laurens , Van Lijsebettens Mieke , Raynaud Cécile , De Veylder Lieven
Published: June 2021

The ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) kinases coordinate the DNA damage response. The roles described for Arabidopsis thaliana ATR and ATM are assumed to be conserved over other plant species, but molecular evidence is scarce. Here, we demonstrate that the functions of ATR and ATM are only partially conserved between Arabidopsis and maize (Zea mays). In both species, ATR and ATM play a key role in DNA repair and cell cycle checkpoint activation, but whereas Arabidopsis plants do not suffer from the absence of ATR under control growth conditions, maize mutant plants accumulate replication defects, likely due to their large genome size. Moreover, contrarily to Arabidopsis, maize ATM deficiency does not trigger meiotic defects, whereas the ATR kinase appears to be crucial for the maternal fertility. Strikingly, ATR is required to repress premature endocycle onset and cell death in the maize endosperm. Its absence results in a reduction of kernel size, protein and starch content, and a stochastic death of kernels, a process being counteracted by ATM. Additionally, while Arabidopsis atr atm double mutants are viable, no such mutants could be obtained for maize. Therefore, our data highlight that the mechanisms maintaining genome integrity may be more important for vegetative and reproductive development than previously anticipated.
GmRAV confers ecological adaptation through photoperiod control of flowering time and maturity in soybean
Authors: Wang Yuhe , Xu Chongjing , Sun Jiafan , Dong Lidong , Li Minmin , Liu Ying , Wang Jianhui , Zhang Xiaoming , Li Dongmei , Sun Jingzhe , Zhang Yuntong , Shan Jinming , Li Wenbin , Zhao Lin
Published: June 2021

Photoperiod strictly controls vegetative and reproductive growth stages in soybean (Glycine max). A soybean GmRAV (Related to ABI3/VP1) transcription factor containing both AP2 and B3 domains was shown to be a key component of this process. We identified six polymorphisms in the GmRAV promoter that showed significant association with flowering time and maturity of soybean in one or multiple environments. Soybean varieties with minor polymorphism exhibited a longer growth period contributing to soybean adaptation to lower latitudes. The cis-acting element GT1CONSENSUS motif of the GmRAV promoter controlled the growth period, and the major allele in this motif shortened duration of late reproductive stages by reducing GmRAV expression levels. Three GmRAV-overexpressing (GmRAV-ox) transgenic lines displayed later ﬂowering time and maturity, shorter height and fewer numbers of leaves compared with control plants, whereas transgenic inhibition of GmRAV expression resulted in earlier ﬂowering time and maturity and increased plant height. Combining DNA affinity purification sequencing and RNA sequencing analyses revealed 154 putative target genes directly bound and transcriptionally regulated by GmRAV. Two GmRAV binding motifs [C(A/G)AACAA(G/T)A(C/T)A(G/T)] and [C(T/A)A(C)C(T/G)CTG] were identiﬁed, and acting downstream of E3E4, GmRAV repressed GmFT5a transcriptional activity through binding a CAACA motif, thereby delaying soybean growth and extending both vegetative and reproductive phases.
Reliability of detection of ultrasound and MRI features of hand osteoarthritis: a systematic review and meta-analysis
Authors: Obotiba Abasiama D , Swain Subhashisa , Kaur Jaspreet , Doherty Michael , Zhang Weiya , Abhishek Abhishek
Published: June 2021

Objectives

To systematically review the literature on inter- and intra-rater reliability of scoring US and MRI changes in hand OA.

Methods

MEDLINE, EMBASE, CINHAL, Web of Science and AMED were searched from inception to January 2020. Kappa (κ), weighted kappa (κw) and intra-class correlation coefficients for dichotomous, semi-quantitative and summated scores, respectively, and their 95% CI were pooled using a random-effects model. Heterogeneity between studies was assessed and reliability estimates were interpreted using the Landis–Koch classification.

Results

Fifty studies met the inclusion criteria (29 US, 17 MRI, 4 involving both modalities). The pooled κ (95% CI) for inter-rater reliability was substantial for US-detected osteophytes [0.66 (0.54, 0.79)], grey-scale synovitis [0.64 (0.32, 0.97)] and power Doppler [0.76, (0.47, 1.05)], whereas intra-rater reliability was almost perfect for osteophytes [0.82 (0.80, 0.84)], central bone erosions (CBEs) [0.83 (0.78, 0.89)] and effusion [0.83 (0.74, 0.91)], and substantial for grey-scale synovitis [0.64 (0.49, 0.79)] and power Doppler [0.70 (0.59, 0.80)]. Inter-rater reliability for dichotomous assessment was substantial for MRI-detected CBEs [0.75 (0.67, 0.83)] and synovitis [0.69 (0.51, 0.87)], slight for osteophytes [0.14 (0.04, 0.25)], and almost perfect for sum score of osteophytes, CBEs, joint space narrowing (JSN), and bone marrow lesions (BMLs) (0.81–0.89). Intra-rater reliability was almost perfect for sum score of MRI synovitis [0.92 (0.87, 0.96)], BMLs [0.88 (0.78, 0.98)], osteophytes [0.86 (0.74, 0.98)], CBEs [0.83 (0.66, 1.00)] and JSN [0.91 (0.87, 0.91)].

Conclusion

US and MRI are reliable in detecting hand OA features. US may be preferred due to low cost and increasing availability.
ASSESSMENT OF NATURAL RADIOACTIVITY LEVELS AND RADIATION EXPOSURE IN NEW BUILDING MATERIALS IN SPAIN
Authors: Mas J L , Ramírez J R Caro , Bermúdez S Hurtado , Fernández C Leiva
Published: June 2021

Novel building materials were manufactured and analyzed for 226Ra, 232Th and 40K using an HPGe gamma-ray spectrometer. The results show that the highest value of 40K was 4530 Bq per kg which was measured in a sample containing fly ashes from olive stones. The highest values of 226Ra and 232Th activities were 181 and 185 Bq per kg, which were measured in a sample with fly ashes from the co-combustion of coal and coke, respectively. On the other hand, the lowest values of 40K, 226Ra and 232Th activities were obtained for samples incorporating mussel shells. The radiological health hazard parameters, such as radium equivalent activity (Raeq), activity concentration index (I), absorbed and effective dose rates, associated with these radionuclides were evaluated. These values are within the EU recommended limits in building materials, except for samples of concrete containing fly ashes from olive stones, coal and coke. This study has contributed to the inclusion of industrial wastes that have not been collected previously in the Naturally Occurring Radioactive Material (NORM) databases on radioactivity of building materials.
Patient-centered behavioral services for women veterans with mental health conditions
Authors: Pebole Michelle M , VanVoorhees Elizabeth E , Chaudhry Nivedita , Goldstein Karen M , Thompson Jillian , Parker Ryan , Caron Kelly M , Hall Katherine S
Published: June 2021

The Veterans Health Administration (VHA) is undergoing a transformational shift from disease-focused care to a Whole Health model that emphasizes physical, mental, emotional, and spiritual health and well-being. As this shift is occurring, women veterans using VHA services face challenges navigating a system that has historically served a primarily male demographic, without consistent consensus on which services require specialization by gender. A quality improvement project was conducted to solicit feedback on VHA behavioral and wellness programs from women veterans enrolled in VHA mental healthcare services. A multi-disciplinary work group of clinical researchers and healthcare providers developed a needs assessment survey to assess patient needs and preferences for behavioral health services. A convenience sample of female veterans using VHA mental healthcare services within a comprehensive Women’s Health Clinic were invited to complete this anonymous survey. 107 women Veterans 18–65+ years old (65.3% African American; 5.9% LatinX; 54.2% aged under 55) completed the survey. Over 50% of patients endorsed relationships, physical activity, sleep/nightmares, pain management, anger, or spiritual/moral pain as top wellness priorities. Programatic preferences included location (located at the main VA Hospital) and gender composition (female only group formats). Schedule conflicts were the most frequently cited barriers. Results from this quality improvement project highlight considerations for tailoring the content and delivery of behavioral services for women veterans with mental health conditions.
News coverage about aspirin as a countervailing force against low-dose aspirin campaign promotion
Authors: Southwell Brian G , Duval Sue , Luepker Russell V , Oldenburg Niki , Van’t Hof Jeremy , Eder Milton , Russell Carol , Graves Robert N , Finnegan John
Published: June 2021

Organized health promotion efforts sometimes compete with news media, social media, and other sources when providing recommendations for healthy behavior. In recent years, patients have faced a complicated information environment regarding aspirin use as a prevention tool for heart health. We explored the possibility that campaign promotion of low-dose aspirin use might have been undermined by news coverage in the USA detailing controversies regarding aspirin use. Using time series data on low-dose aspirin sales in Minnesota, USA, we assessed whether news coverage of aspirin or audience engagement with the Ask About Aspirin campaign website predicted subsequent changes in low-dose aspirin sales, over and above any secular trend. News coverage predicted actual low-dose aspirin purchases whereas exposure to a state-level campaign did not. While a campaign effort to encourage people at risk to discuss low-dose aspirin use with their health care providers did not generate substantive changes in low-dose aspirin tablet sales in the areas of Minnesota monitored for this study, past news coverage about aspirin use, including news about negative side effects, may have suppressed low-dose aspirin sales during this same period. The extent of news coverage about aspirin and heart health had a negative effect on tablet sales recorded in greater Minnesota approximately a month later in an ARIMA time series model, coefficient = −.014, t = −2.33, p = .02. Presented evidence of news coverage effect suggests health campaign assessment should consider trends in the public information environment as potential countervailing forces.
Potato Virus Y Biological Strain Group YD: Hypersensitive Resistance Genes Elicited and Phylogenetic Placement
Authors: Jones Roger A. C. , Barbetti Martin J. , Fox Adrian , Adams Ian P.
Published: June 2021

Potato virus Y (PVY) disrupts healthy seed potato production and causes tuber yield and quality losses globally. Its subdivisions consist of strain groups defined by potato hypersensitive resistance (HR) genes and whether necrosis occurs in tobacco, and phylogroups defined by sequencing. When PVY isolate PP was inoculated to potato cultivar differentials with HR genes, the HR phenotype pattern obtained resembled that caused by strain group PVYDisolate KIP1. A complete genome of isolate PP was obtained by high-throughput sequencing. After removal of its short terminal recombinant segment, it was subjected to phylogenetic analysis together with 30 complete nonrecombinant PVY genomes. It fitted within the same minor phylogroup PVYO3subclade as KIP1. Putative HR gene Nd was proposed previously to explain the unique HR phenotype pattern that developed when differential cultivars were inoculated with PVYD. However, an alternative explanation was that PVYDelicits HR with HR genes Nc and Ny instead. To establish which gene(s) it elicits, isolates KIP1 and PP were inoculated to F1potato seedlings from (i) crossing ‘Kipfler’ and ‘White Rose’ with ‘Ruby Lou’ and (ii) self-pollinated ‘Desiree’ and ‘Ruby Lou’, where ‘Kipfler’ is susceptible (S) but ‘White Rose’, ‘Desiree’, and ‘Ruby Lou’ develop HR. With both isolates, the HR:S segregation ratios obtained fitted 5:1 for ‘Kipfler’ × ‘Ruby Lou’, 11:1 for ‘White Rose’ × ‘Ruby Lou’, and 3:1 for ‘Desiree’. Those for ‘Ruby Lou’ were 68:1 (isolate PP) and 52:0 (isolate KIP1). Because potato is tetraploid, these ratios suggest PVYDelicits HR with Ny from ‘Ruby Lou’ (duplex condition) and ‘Desiree’ (simplex condition) and Nc from ‘White Rose’ (simplex condition) but provide no evidence that Nd exists. Therefore, our differential cultivar inoculations and inheritance studies highlight that PVYDisolates elicit an HR phenotype in potato cultivars with either of two HR genes Nc or Ny, so putative gene Nd can be discounted. Moreover, phylogenetic analysis placed isolate PP within the same minor phylogroup PVYO3subclade as KIP1, which constitutes the most basal divergence within overall major phylogroup PVYO.
Inpatient Staffing Dashboard
Authors: Role Jethrone , Chao Hong , Rosario Chris , Ho Phillip , Hodgkins Marie
Published: June 2021

Inadequate staffing negatively impacts hospital operations, quality of patient care, and employee engagement. Traditional staffing approaches to address clinical staffing and scheduling are not as effective in a complex healthcare environment. Organizations must leverage innovative strategies and use of technology to improve clinical staffing. To address the staffing challenges, nursing staffing and information technology at Loma Linda University Medical Center developed an inpatient staffing dashboard. A staffing dashboard is a staffing tool comprised of several tabs and staffing measures, which include filled percentage as the key performance indicator. During the staffing dashboard development, evaluation took place to determine the staffing and scheduling system's extract-transform-load capacity. Data were analyzed, defined, and profiled. Tableau software was used to create an interactive staffing dashboard and integrated with EPIC Hyperspace for user accessibility. The interactive features and staffing measures available in this staffing tool empowered staffing and nursing leaders to utilize data visualization for day-to-day nursing operations, proactively plan for staffing demands, and use data to drive staffing decisions. Our collaborative experience proved that nursing and information technology collaborative projects produce innovative solutions and workflow efficiencies. Leaders must promote nursing–information technology collaborations in healthcare organizations.
A Simple, Novel Prognostic Score in Platinum Sensitive Relapsed Ovarian Cancer
Authors: Goenka Luxitaa , Nakka Thejeshwar , Dubashi Biswajit , Kayal Smita , Penumadu Prasanth , Chaturvedula Latha , Veena Pampapati , Durairaj Jayalakshmi , Ganesan Prasanth
Published: June 2021

Objectives:

Epithelial ovarian cancer is one of the commonest gynecologic cancers and one with the highest mortality. This retrospective cohort study was done to identify predictors of outcomes in platinum-sensitive relapsed ovarian cancer patients (PS-ROC).

Methods:

Data regarding baseline characters, laboratory findings, therapeutic details and survival outcomes was obtained from the medical records of PS-ROC patients presented between January 2015 and December 2019. Prognostic score was constructed using factors which were significant on multivariate analysis to predict survival outcomes.

Results:

A total of 71 (PS-ROC) patients were included in the study with a median age of 50 years. Relapse treatment was either chemotherapy alone (n=53, 75%) or chemotherapy plus surgery (n=18, 25%). The estimated progression-free survival (PFS) and overall survival were 10 and 29 months, respectively. The overall response rate after treatment of relapse was 59%. Prognostic score was created with the 3 factors (each scoring 1 point) which were predictive of PFS (higher lymphocyte-monocyte ratio, longer platinum-free interval and secondary cytoreduction). Patients with low score (0,1) had better PFS than those with higher score (2,3) (13 vs. 7 mo [P=0.0001]).

Conclusions:

A composite prognostic score could predict outcomes in PS-ROC and potentially identify a subgroup with very poor prognosis. Future studies with a greater number of patients are needed to validate these findings. This information could help tailor more intense therapies to the high-risk patients and attempt to improve outcomes and serve as stratification factors for prospective trials.
High-dose Chemotherapy in Germ Cell Cancer Patients With Brain Metastases
Authors: Delaye Matthieu , Benderra Marc-Antoine , Deforceville Louise , Larghero Jérôme , Parquet Nathalie , Culine Stéphane , Grazziotin-Soares Daniele , Lotz Jean-Pierre
Published: June 2021

Objectives:

Germ cell tumor (GCT) patients with brain metastases (BM) have a poor prognosis and high risk of treatment failure. Optimal therapies for these patients remain controversial. The aim of this study was to report the outcomes of all GCT patients with BM treated with high-dose chemotherapy (HDCT) in our French expert center for GCT.

Methods:

We carried out a retrospective study of 35 GCT patients with BM who were treated from 2003 to 2019 with HDCT, followed by infusions of autologous peripheral blood hematopoietic stem cells.

Results:

The overall survival at 2 years was 36.9% (95% confidence interval, 19.7-54). The median overall survival was 12 months and the median progression-free survival was 8 months. No variables were associated with better survival in the univariable analysis. Among the 35 patients included in our study, 31 completed HDCT and 4 stopped treatments after mobilization. Eleven patients (11) showed favorable responses (complete, partial, or stable disease) to HDCT and 20 patients died of disease progression (17) or toxicities (3). Among the 11 patients with favorable responses to HDCT, 8 (72.7%) had metachronous BM, mostly isolated. The majority of these patients did not receive local treatment at diagnosis or at relapse.

Conclusions:

Together, our study reveals that GCT patients can experience long-term survival even in the presence of BM. Metachronous BM can also be cured with HDCT even in the absence of local treatment. Biological and radiologic responses to mobilization could be a predictor of favorable responses to HDCT.
Preferences for Prophylactic Oral Antibiotic Use in Dermatologic Surgery: A Multicenter Discrete Choice Experiment
Authors: Aizman Leora , Barbieri John S. , Feit Elea M. , Lukowiak Tess M. , Perz Allison M. , Shin Thuzar M. , Miller Christopher J. , Golda Nicholas , Leitenberger Justin J. , Carr David R. , Nijhawan Rajiv I. , Hasan Aliza , Eisen Daniel B. , Etzkorn Jeremy R.
Published: June 2021

BACKGROUND

Antibiotics are often prescribed after dermatologic surgery for infection prophylaxis, but patient preferences about prophylactic antibiotics are not well understood.

OBJECTIVE

To understand patient preferences about taking antibiotics to prevent surgical site infection (SSI) relative to antibiotic efficacy and antibiotic-associated adverse drug reactions.

MATERIALS AND METHODS

Multi-center, prospective discrete choice experiment (DCE).

RESULTS

Three hundred thirty-eight respondents completed the survey and DCE. 54.8% of respondents preferred to take an antibiotic if it reduced the SSI rate from 5% to 2.5% and if the risk of adverse drug reactions was low (1% risk gastrointestinal upset, 0.5% risk itchy skin rash, 0.01% risk emergency department visit). Even if an antibiotic could eliminate SSI risk (0% risk SSI) and had a low adverse drug reaction profile, 26.7% of respondents prefer not to take prophylactic oral antibiotics.

CONCLUSION

Risk–benefit thresholds for taking antibiotics to prevent SSI vary widely. Clinical trials are needed to better characterize the effectiveness and risks of oral antibiotic SSI prophylaxis to guide decision-making. Future studies should also evaluate whether shared decision-making can improve the patient experience.
Safety of Phosphodiesterase-5 Inhibitors in Valvular Heart Disease
Authors: Gopal Aaron , Sharma Tarun , Calkins Joe B.
Published: June 2021

Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction, not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects that can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Although some contraindications to the use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in the presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease.