bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple genetic architecture and low constraint allows rapid floral evolution in a diverse and recently radiating plant genus
Authors: Kostyun Jamie L. , Gibson Matthew J.S. , King Christian M. , Moyle Leonie C. 
Published: January 2019

SummaryGenetic correlations among different components of phenotypes, especially resulting from pleiotropy, can constrain or facilitate trait evolution. These factors could especially influence the evolution of traits that are functionally integrated, such as those comprising the flower. Indeed, pleiotropy is proposed as a main driver of repeated convergent trait transitions, including the evolution of phenotypically-similar pollinator syndromes.We assessed the role of pleiotropy in the differentiation of floral and other reproductive traits between two species—Jaltomata sinuosaandJ. umbellata(Solanaceae)—that have divergent suites of floral traits consistent with bee- and hummingbird-pollination, respectively. To do so, we generated a hybrid population and examined the genetic architecture (trait segregation and QTL distribution) underlying 25 floral and fertility traits.We found that most floral traits had a relatively simple genetic basis (few, predominantly additive, QTL of moderate to large effect), as well as little evidence of antagonistic pleiotropy (few trait correlations and QTL co-localization, particularly between traits of different classes). However, we did detect a potential case of adaptive pleiotropy among floral size and nectar traits.These mechanisms may have facilitated the rapid floral trait evolution observed withinJaltomata, and may be a common component of rapid phenotypic change more broadly.
Binding of an X-specific condensin correlates with a reduction in active histone modifications at gene regulatory elements
Authors: Street Lena Annika , Morao Ana Karina , Winterkorn Lara Heermans , Jiao Chen-Yu , Albritton Sarah Elizabeth , Sadic Mohammed , Kramer Maxwell , Ercan Sevinç 
Published: January 2019

ABSTRACTCondensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In C. elegans,, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using ChIP-seq and mRNA-seq. Across the X, DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.SUMMARYCondensins are evolutionarily conserved protein complexes that mediate chromosome condensation during cell division and have been implicated in gene regulation during interphase. Here, we analyzed the gene regulatory role of an X-specific condensin (DCC) in C. elegans, by measuring its effect on histone modifications associated with transcription regulation. We found that in X-to-autosome fusion chromosomes, DCC spreading into autosomal sequences locally reduces gene expression, establishing a direct link between DCC binding and repression. DCC is required for reduced levels of histone modifications associated with transcription activation at X chromosomal promoters and enhancers. These results are consistent with a model whereby DCC binding directly or indirectly results in a reduction in the activity of X chromosomal gene regulatory elements through specific activating histone modifications.
Genomic signatures of somatic hybrid vigor due to heterokaryosis in the oomycete pathogen,Bremia lactucae
Authors: Fletcher Kyle , Gil Juliana , Bertier Lien D , Kenefick Aubrey , Wood Kelsey J , Zhang Lin , Reyes-Chin-Wo Sebastian , Cavanaugh Keri , Tsuchida Cayla , Wong Joan , Michelmore Richard 
Published: January 2019

AbstractLettuce downy mildew caused byBremia lactucaeis the most important disease of lettuce globally. This oomycete pathogen is highly variable and has rapidly overcome resistance genes and fungicides deployed in attempts to control it. The described high-quality genome assembly ofB. lactucaeprovides the foundation for detailed understanding of this economically important pathogen. The biotrophic nature ofB. lactucaecoupled with high levels of heterozygosity and the recently expanded repeat content made genome assembly challenging. The combined use of multiple read types, including synthetic long reads, single molecule sequences, and Hi-C, resulted in a high-quality, chromosome-scale, consensus assembly of this diploid organism. Phylogenetic analysis supports polyphyly in the downy mildews consistent with the biotrophic mode of pathogenesis evolving more than once in the Peronosporaceae. Flow cytometry plus resequencing of 30 field isolates as well as sexual offspring and asexual derivatives from multinucleate single sporangia demonstrated a high incidence of heterokaryosis inB. lactucae. Heterokaryons have phenotypic differences and increased fitness compared to homokaryotic derivatives. Consequently,B. lactucaeexhibits somatic hybrid vigor and selection should be considered as acting on a population of nuclei within coenocytic mycelia. This provides evolutionary flexibility to the pathogen enabling rapid adaptation to different repertoires of host resistance genes and other challenges. The advantages of asexual persistence of heterokaryons may have been one of the drivers of selection that resulted in the loss of uninucleate zoospores in multiple downy mildews.
MroQ is a Novel Abi-domain Protein That Influences Virulence Gene Expression in Staphylococcus aureus via Modulation of Agr Activity
Authors: Marroquin Stephanie , Gimza Brittney , Tomlinson Brooke , Stein Michelle , Frey Andrew , Keogh Rebecca A. , Zapf Rachel , Todd Daniel A. , Cech Nadja B. , Carroll Ronan K. , Shaw Lindsey N. 
Published: January 2019

AbstractNumerous factors have to date been identified as playing a role in the regulation of Agr activity in S. aureus, including transcription factors, antisense RNAs, and host elements. Herein we investigate the product of SAUSA300_1984 (termed MroQ), a transmembrane Abi-domain/M79 protease-family protein, as a novel effector of this system. Using a USA300 mroQ mutant we observed a drastic reduction in proteolysis, hemolysis and pigmentation that was fully complementable. This appears to result from diminished agr activity, as transcriptional analysis revealed significant decreases in expression of both RNAII and RNAIII in the mroQ mutant. Such effects appear to be direct, rather than indirect, as known agr effectors demonstrated limited alterations in their activity upon mroQ disruption. A comparison of RNA-sequencing datasets for both mroQ and agr mutants reveal a profound overlap in their regulomes, with the majority of factors affected being known virulence determinants. Importantly, the preponderance of alterations in expression were more striking in the agr mutant, indicating that MroQ is necessary, but not sufficient, for Agr function. Mechanism profiling revealed that putative residues for metalloprotease activity within MroQ are required for its Agr controlling effect, however this is not wielded at the level of AgrD processing. Virulence assessment demonstrated that mroQ and agr mutants both exhibited increased formation of renal abscesses, but decreased skin abscess formation, alongside diminished dermonecrosis. Collectively, we present the characterization of a novel agr effector in S. aureus, which would appear to be a direct regulator, potentially functioning via interaction with the AgrC histidine kinase.
From the clinic to the bench and back again in one dog year: identifying new treatments for sarcoma using a cross-species personalized medicine pipeline
Authors: Rao Sneha , Somarelli Jason A. , Altunel Erdem , Selmic Laura E. , Byrum Mark , Sheth Maya U. , Cheng Serene , Ware Kathryn E. , Kim So Young , Prinz Joseph A. , Devos Nicolas , Corcoran David L. , Moseley Arthur , Soderblom Erik , Hsu S. David , Eward William C. 
Published: January 2019

AbstractCancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identifying personalized treatments; however, for rare cancers, such as sarcomas, access to patient samples can be extremely limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up less than 1% of all cancers in humans, sarcomas represent at least 15% of all cancers in dogs. Dogs with naturally-occurring sarcomas also have intact immune systems, an accelerated pace of cancer progression, and share the same environment as humans, making them ideal models that bridge key gaps between mouse models and human sarcomas.Here, we develop a framework for a personalized medicine pipeline that integrates drug screening, validation, and genomics to identify new therapies. We tested this paradigm through the study of a pet dog, Teddy, who presented with six synchronous leiomyosarcomas. By integrating patient-derived cancer models, in vitro drug screens, and in vivo validation we identified proteasome inhibitors as a potential therapy for Teddy. After showing an initial response to the proteasome inhibitor, bortezomib, Teddy developed rapid resistance, and tumor growth resumed. Whole exome sequencing revealed substantial genetic heterogeneity across Teddy’s multiple recurrent tumors and metastases, suggesting that intra-patient heterogeneity was responsible for the heterogeneous clinical response. Ubiquitin proteomics coupled with exome sequencing revealed multiple candidate driver mutations in proteins related to the proteasome pathway. Together, our results demonstrate how the comparative study of canine sarcomas can offer rapid insights into the process of developing personalized medicine approaches that can lead to new treatments for sarcomas in both humans and canines.
Attractor competition enriches cortical dynamics during awakening from anesthesia
Authors: Tort-Colet Núria , Capone Cristiano , Sanchez-Vives María V. , Mattia Maurizio 
Published: January 2019

AbstractCortical slow oscillations (≲ 1 Hz) are a hallmark of slow-wave sleep and deep anesthesia across animal species. They arise from spatiotemporal patterns of activity with low degree of complexity, eventually increasing as wakefulness is approached and cognitive functions emerge. The arousal process is then an open window on the widely unknown mechanisms underlying the emergence of the dynamical richness of awake cortical networks. Here, we investigated the changes in the network dynamics as anesthesia fades out and wakefulness is approached in layer 5 neuronal assemblies of the rat visual cortex. Far from being a continuum, this transition displays both gradual and abrupt activity changes. Starting from deep anesthesia, slow oscillations increase their frequency eventually expressing maximum regularity. This stage is followed by the abrupt onset of an infra-slow (~ 0.2 Hz) alternation between sleep-like oscillations and activated states. A population rate model reproduces this transition driven by an increased excitability that brings it to periodically cross a critical point. We conclude that dynamical richness emerges as a competition between two metastable attractor states whose existence is here experimentally confirmed.
Competency assessment of the medical interns and nurses and prevailing practices to provide family planning services in teaching hospitals in three states of India
Authors: Gupta Madhu , Verma Madhur , Kaur Kiranjit , Iyengar Kirti , Singh Tarundeep , Singh Anju 
Published: January 2019

AbstractObjectivesThe objectives of the study was to assess the knowledge and skills of medical interns and nurses regarding family planning (FP) services, and document the prevailing FP practices in the teaching hospitals in India.Study DesignA cross-sectional study was conducted in three states (Delhi, Rajasthan, and Maharashtra) of India, among randomly selected 163 participants, including medical interns (n=81) and in-service nurses (n=82), during 2017. Semi-structured, pre-tested interview schedule, was used to assess the knowledge and status of training received; and objective structured clinical examination (OSCE) based checklist was used to assess the skills.ResultsAbout 60% of the interns and 48% of the nurses knew more than five contraceptives that could be offered to the clients. About 22% (11.1% interns and 33.3% nurses) respondents believed that contraceptives should not be given to a married woman coming alone, and 31.9% (17.3% interns and 46.3% nurses) respondents reported that it was illegal to provide contraceptives to unmarried people. Nearly 43.3% interns and 69.5% nurses refused to demonstrate intrauterine contraceptive device (IUCD) insertion in the dummy uterus as per OSCE, and among those who did, 12.3% interns and 18.3% nurses had failed. About 63% interns and 63.4% of nurses had observed IUCD insertion, and 12.3% interns and 17.1% had performed IUCD insertion, during their training.ConclusionsKnowledge and skills of interns and nurses regarding FP services were only partial. The medical training during graduation or internship, and during the job, was found to be inadequate to provide quality FP services.ImplicationsThe partial knowledge and skills of medical interns and nurses regarding family planning services indicated inadequate training received, and substandard quality of services rendered by them, which may put the universal access to sexual and reproductive health care services and rights in the developing countries at risk.
Left Pulmonary Artery in 22q11.2 deletion syndrome. Echocardiographic evaluation in patients without cardiac defects and role of Tbx1 in mice
Authors: Mastromoro Gioia , Calcagni Giulio , Versacci Paolo , Putotto Carolina , Chinali Marcello , Lambiase Caterina , Unolt Marta , Pelliccione Elena , Anaclerio Silvia , Caprio Cinzia , Cioffi Sara , Bilio Marchesa , Baban Anwar , Drago Fabrizio , Digilio Maria Cristina , Marino Bruno , Baldini Antonio 
Published: January 2019

ABSTRACTIntroduction and HypothesisPatients with 22q11 deletion syndrome (22q11.2DS) present, in about 75% of cases, typical patterns of cardiac defects, with a particular involvement on the ventricular outflow tract and great arteries. However, in this genetic condition the dimensions of the pulmonary arteries (PAs) never were specifically evaluated.We measured both PAs diameter in patients with 22q11.2DS without cardiac defects, comparing these data to a normal control group. Moreover, we measured the PAs diameter in Tbx1 mutant mice. Finally, a cell fate mapping in Tbx1 mutants was used to study the expression of this gene in the morphogenesis of PAs.MethodsWe evaluated 58 patients with 22q11.2DS without cardiac defects. The control group consisted of 54 healthy subjects, matched for age and sex. All cases underwent a complete transthoracic echocardiography. Moreover, we crossed Tbx1+/- mice and harvested fetuses. We examined the cardiovascular phenotype of 8 wild type (WT), 37 heterozygous (Tbx1+/-) and 6 null fetuses (Tbx1-/-). Finally, we crossed Tbx1Cre/+mice with R26RmT-mG Cre reporter mice to study Tbx1 expression in the pulmonary arteries.ResultsThe echocardiographic study showed that the mean of the LPA/RPA ratio in 22q11.2DS was smaller (0.80 ± 0.12) than in controls (0.97 ± 0.08; p < 0.0001).Mouse studies resulted in similar data as the size of LPA and RPA was not significantly different in WT embryos, but in Tbx1+/- and Tbx1-/- embryos the LPA was significantly smaller than the RPA in both mutants (P=0.0016 and 0.0043, respectively). We found that Tbx1 is expressed near the origin of the PAs and in their adventitia.ConclusionsChildren with 22q11.2DS without cardiac defects show smaller LPA compared with healthy subjects. Mouse studies suggest that this anomaly is due to haploinsufficiency of Tbx1. These data may be useful in the clinical management of children with 22q11.2DS and should guide further experimental studies as to the mechanisms underlying PAs development.
Modeling impacts of climate change on the potential habitat of an endangered Brazilian endemic coral: discussion about deep sea refugia
Authors: de Oliveira Umberto Diego Rodrigues , de Lima Gislaine Vanessa , Gomes Paula Braga , Cordeiro Ralf Tarciso Silva , Pérez Carlos Daniel 
Published: January 2019

AbstractClimate and environmental changes are determinant for coral distribution and their very existence. Effects of such changes on distribution can be predicted through ecological niche models, anticipating suitable habitats for subsistence of species.Mussismilia harttiiis one of the most widespread Brazilian endemic reef building corals, and in increasing risk of extinction. The ecological niche models were used through the maximal entropy approach to determine the potential present and future habitats forM. harttii, estimating suitable habitat losses and gains at the end of the 21st century. For this purpose, records published in the last 20 years and current and future environmental variables were correlated. The models were evaluated through the Area Under the Operational Curve of the Receiver, using the AUC values and additionally AUCratio, a new approach using independent occurrence data. Both approaches showed that the models performed satisfactorily in predicting areas of potential habitat for the species. The results showed that the area to the south of the São Francisco River is the most suitable for the current habitat of the species, and that nitrate was the most influential variable for the models. Simultaneously, the salinity and temperature exerted greater influence for the models in future scenarios, in which current northernmost and southernmost limits of the potential habitats shifted towards deeper regions, so these deeper sites may serve as a refugia for the species in global warming scenarios. Coral communities at such depths would be less susceptible to the impacts of climate change on temperature and salinity. However, deep sea is not free from human impacts and measures to protect deeper ecosystems should be prioritized in environmental policy for Brazilian marine conservation.
Doublecotin-like kinase 1 increases chemoresistance of colorectal cancer cells through the anti-apoptosis pathway
Authors: Li Lianna , Jones Kierra , Mei Hao 
Published: January 2019

AbstractColorectal cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths in the United States. About 50% of CRC patients relapsed after surgical resection and ultimately died of metastatic disease. Cancer stem cells (CSCs) are believed to be the primary reason for the recurrence of CRC. Specific stem cell marker, doublecortin-like kinase 1 (DCLK1) plays critical roles in initiating tumorigenesis, facilitating tumor progression, and promoting metastasis of CRC. It is up-regulated in CRC and up-regulation of DCLK1 indicates poor prognosis. Whether DCLK1 is correlated with enhanced chemoresistance of CRC cells is unclear. Our research aims to reveal association of DCLK1 with chemoresistance of CRC cells and the underlying molecular mechanisms. In order to achieve our goal, we established stable DCLK1 over-expression cells (DCLK1+) using the HCT116 cells (WT). DCLK1+ and WT cells were treated with 5-Fluorouracil (5-Fu) at different doses for 24 or 48 hours. MTT assay was used to evaluate cell viability and IC50 of 5-Fu was determined. Quantitative real time PCR was applied to determine gene expression of caspase-3 (casp-3), caspase-4 (casp-4), and caspase-10 (casp-10). Cleaved casp-3 expression was investigated using Western blot and immunofluorescence. Our results demonstrated that IC50 of 5-Fu for the DCLK1+ cells was significantly higher than that of the WT cells for both 24 and 48-hour treatment (P=0.002 and 0.048 respectively), indicating increased chemoresistance of the DCLK1+ cells. Gene expression of casp-3, casp-4, and casp-10 were significantly inhibited in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (P=7.616e-08, 1.575e-05 and 5.307e-08, respectively). Cleaved casp-3 amount and casp-3 positive cells were significantly decreased in the DCLK1+ cells after 5-Fu treatment compared to the WT cells (P=0.015). In conclusion, our results demonstrated that DCLK1 overexpression enhanced the chemoresistance of CRC cells to 5-Fu treatment by suppressing gene expression of key caspases in the apoptosis pathway and activation of apoptosis pathway. DCLK1 can be an intriguing therapeutic target for the effective treatment of CRC patients.
What drives green persistence intentions?
Authors: Wu Hung-Che , Cheng Ching-Chan 
Published: January 2019

PurposeThe purpose of this paper is to explore the structural relationship between green persistence intentions and their seven drivers – green authenticity, green perceptual evaluation, green co-creation, green experiential memorability, green experiential satisfaction, green passionate love and green need for cognition in a green hotel context.Design/methodology/approachThe data used in this study were based on a sample of 589 customers staying at one green hotel in New Taipei City of Taiwan. The predicted relationship was tested using the structural equation modeling and the hierarchical regression analysis.FindingsThe results indicate that green perceptual evaluation, green co-creation and green experiential memorability influence green experiential satisfaction. Green passionate love is influenced by green experiential satisfaction. Green need for cognition moderates the effect of green experiential satisfaction on green persistence intentions. Green persistence intentions are influenced by green experiential satisfaction and green passionate love.Practical implicationsTo increase green authenticity, green perceptual evaluation, green co-creation, green experiential memorability, green experiential satisfaction, green passionate love, green need for cognition and green persistence intentions, the study findings will help green hotels to develop and implement market-orientated product and/or service strategies.Originality/valueThis paper provides data that lead to a better understanding of the relationships among green authenticity, green perceptual evaluation, green co-creation, green experiential memorability, green experiential satisfaction, green passionate love, green need for cognition and green persistence intentions in a green hotel context.