bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient lentiviral transduction of different human and mouse cells
Authors: Zhang Gang , Wang Taihua 
Published: January 2018

AbstractBackgroundLentiviral vectors (LVs) allowing efficient establishment of stable transgene overexpression mammalian and human cell lines are invaluable tools for genetic research. Currently, although LV transductions are broadly adopted, they are often limited due to their low titers for efficient transduction.ResultsHere, we described a set of optimized, efficient techniques, which could produce sufficiently high LV titers, and, provide efficient transduction of cells. According to these optimizations, most of the mammalian and human cells, both primary cells and cell lines, could be transduced successfully with high levels of transgene stable expression, including both constitutive and induced expressions.ConclusionsOur data demonstrated the highly usefulness of our optimized methods. Therefore, this study provided an efficient method for most of LV transduction experiments in vitro.
A molecular network for functional versatility ofHECATEtranscription factors
Authors: Gaillochet Christophe , Jamge Suraj , van der Wal Froukje , Angenent Gerco , Immink Richard , Lohmann Jan U. 
Published: January 2018

SummaryDuring the plant life cycle, diverse signalling inputs are continuously integrated and engage specific genetic programs depending on the cellular or developmental context. Consistent with an important role in this process, HECATE (HEC) bHLH transcription factors display diverse functions, from photomorphogenesis to the control of shoot meristem dynamics and gynoecium patterning. However, the molecular mechanisms underlying their functional versatility and the deployment of specific HEC sub-programs still remain elusive.To address this issue, we systematically identified proteins with the capacity to interact with HEC1, the best characterized member of the family, and integrated this information with our data set of direct HEC1 target genes. The resulting core genetic modules were consistent with specific developmental functions of HEC1, including its described activities in light signalling, gynoecium development and auxin homeostasis. Importantly, we found that in addition,HECgenes play a role in the modulation of flowering time and uncovered that their role in gynoecium development may involve the direct transcriptional regulation ofNGATHA1 (NGA1)andNGA2genes. NGA factors were previously shown to contribute to fruit development, but our data now show that they also modulate stem cell homeostasis in the SAM.Taken together, our results suggest a molecular network underlying the functional versatility of HEC transcription factors. Our analyses have not only allowed us to identify relevant target genes controlling shoot stem cell activity and a so far undescribed biological function of HEC1, but also provide a rich resource for the mechanistic elucidation of further context dependent HEC activities.Significance statementAlthough many transcription factors display diverse regulatory functions during plant development, our understanding of the underlying mechanisms remains poor. Here, by reconstructing the regulatory modules orchestrated by the bHLH transcription factor HECATE1 (HEC1), we defined its regulatory signatures and delineated a regulatory network that provides a molecular basis for its functional versatility. In addition, we uncovered a function forHECgenes in modulating flowering time and further identified downstream signalling components balancing shoot stem cell activity.
OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development
Authors: Hrit Joel , Li Cheng , Martin Elizabeth Allene , Simental Eric , Goll Mary , Panning Barbara 
Published: January 2018

AbstractTET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activityin vitro.We identify a domain of TET1 responsible for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that the TET1-OGT interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET-containing high molecular weight complexes and causes widespread gene expression changes. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.
Dawn and photoperiod sensing by phytochrome A
Authors: Seaton Daniel D , Toledo-Ortiz Gabriela , Kubota Akane , Ganpudi Ashwin , Imaizumi Takato , Halliday Karen J 
Published: January 2018

AbstractIn plants, light receptors play a pivotal role in photoperiod sensing, enabling them to track seasonal progression. Photoperiod sensing arises from an interaction between the plant’s endogenous circadian oscillator and external light cues. Here, we characterise the role of phytochrome A (phyA) in photoperiod sensing. Our meta-analysis of functional genomic datasets identified phyA as a principal transcriptional regulator of morning-activated genes, specifically in short photoperiods. We demonstrate that PHYA expression is under the direct control of the PHYTOCHROME INTERACTING FACTOR transcription factors, PIF4 and PIF5. As a result, phyA protein accumulates during the night, especially in short photoperiods. At dawn phyA activation by light results in a burst of gene expression, with consequences for anthocyanin accumulation. The combination of complex regulation of PHYA transcript and the unique molecular properties of phyA protein make this pathway a sensitive detector of both dawn and photoperiod.Significance statementThe changing seasons subject plants to a variety of challenging environments. In order to deal with this, many plants have mechanisms for inferring the season by measuring the duration of daylight in a day. A number of well-known seasonal responses such as flowering are responsive to daylength or photoperiod. Here, we describe how the photoreceptor protein phytochrome A senses short photoperiods. This arises from its accumulation during long nights, as happens during winter, and subsequent activation by light at dawn. As a result of this response, the abundance of red anthocyanin pigments is increased in short photoperiods. Thus, we describe a mechanism underlying a novel seasonal phenotype in an important model plant species.
Individual repeatability and heritability of divorce in a wild population
Authors: Germain Ryan R. , Wolak Matthew E. , Reid Jane M. 
Published: January 2018

ABSTRACTUnderstanding micro-evolutionary responses of mating systems to contemporary selection requires estimating sex-specific additive genetic variances and cross-sex genetic covariances in key reproductive strategy traits. One key trait comprises the occurrence of divorce versus mate-fidelity across sequential reproductive attempts. If divorce represents an evolving behavioural strategy it must have non-zero individual repeatability and heritability, but quantitative estimates from wild populations are scarce. We used 39 years of individual breeding records and pedigree data from free-living song sparrows (Melospiza melodia) to quantify sex-specific permanent individual and additive genetic variances, and hence estimate repeatability and heritability, in liability for divorce. We estimated moderate repeatability in females, but little repeatability in males. Estimates of additive genetic variance were small in both sexes, and the cross-sex genetic covariance was close to zero. However, the total heritability was likely non-zero but small, indicating low potential for micro-evolutionary response to selection. Rapid micro-evolution of divorce rate therefore appears unlikely, even if there were substantial fitness benefits of divorce and resulting selection.
Exposure to the oral host niche yields rapid phenotypic and genotypic diversification in Candida albicans
Authors: Forche A. , Cromie G. , Gerstein A.C. , Solis N. V. , Pisithkul Z. , Srifa W. , Jeffery E. , Filler S.G. , Dudley A.M. , Berman J. 
Published: January 2018

AbstractIn vitro studies suggest that stress may generate random standing variation, and that different cellular and ploidy states may evolve more rapidly under stress. Yet this idea has not been tested with pathogenic fungi growing within their host niche in vivo. Here, we analyzed the generation of both genotypic and phenotypic diversity during exposure of Candida albicans to the mouse oral cavity. Ploidy, aneuploidy, loss of heterozygosity (LOH) and recombination were determined using flow cytometry and ddRADseq. Colony phenotypic changes (CPs) in size and filamentous growth were evident without selection, and were enriched among colonies selected for LOH of the GAL1 marker. Aneuploidy and LOH occurred on all chromosomes (Chrs), with aneuploidy more frequent for smaller Chrs and whole Chr LOH more frequent for larger Chrs. Large genome shifts in ploidy to haploidy often maintained one or more heterozygous disomic Chrs, consistent with random Chr missegregation events. Most isolates displayed several different types of genomic changes, suggesting that the oral environment rapidly generates diversity de novo. In sharp contrast, following in vitro propagation isolates were not enriched for multiple LOH events, except in those that underwent haploidization and/or had high levels of Chr loss. The frequency of events was overall 100 times higher for C. albicans populations following in vivo passage compared to in vitro. These hyperdiverse in vivo isolates likely provide C. albicans with the ability to adapt rapidly to the diversity of stress environments it encounters inside the host.Author summaryAdaption is a continuous dynamic process that requires genotypic and phenotypic variation. Here we studied the effects of a single passage in a mouse oropharyngeal model of infection on the appearance of diversity in C. albicans, a common commensal of the human oral cavity and GI tract. We found that variation could be rapidly detected following oral colonization, with the frequency of genome change being considerably higher with pre-selection for recombination and colony phenotypic changes. Importantly, one third of all isolates had multiple genome changes, significantly higher than expected by chance alone. We suggest that some cells in the population are naturally hypervariable and that they are a major source of diversity upon which selection can act in stressful conditions in vivo and in vitro.
Genetics behind the biosynthesis of nonulosonic acid containing lipooligosaccharides inCampylobacter coli
Authors: Kolehmainen Alejandra , Rossi Mirko , Stupak Jacek , Li Jianjun , Gilbert Michel , Wakarchuk Warren 
Published: January 2018

ABSTRACTCampylobacter jejuniandCampylobacter coliare the most common cause of bacterial gastroenteritis in the world. Ganglioside mimicry byC. jejunilipooligosaccharide (LOS) is the triggering factor of Guillain-Barré syndrome (GBS), an acute polyneuropathy. Sialyltransferases from the glycosyltransferase (GT) family 42 are essential for the expression of ganglioside mimics inC. jejuni. Recently, two novel GT-42 genes,cstIVandcstV, have been identified inC. coli.Despite being present in ∼11% of currently availableC. coligenomes, the biological role ofcstIVandcstVis unknown. In the present study, mutation studies in two strains expressing eithercstIVorcstVwere performed and mass spectrometry was used to investigate differences in the chemical composition of LOS. Attempts were made to identify donor and acceptor molecules usingin vitroactivity tests with recombinant GT-42 enzymes. Here, we show that CstIV and CstV are involved inC. coliLOS biosynthesis. In particular,cstVis associated with LOS sialylation, whilecstIVis linked to the addition of a diacetylated nonulosonic acid residue.IMPORTANCEDespite being a major foodborne pathogen,Campylobacter coliglycobiology has been largely neglected. The genetic makeup of theC. colilipooligosaccharide biosynthesis locus was largely unknown until recently.C. coliharbour a large set of genes associated to lipooligosaccharide biosynthesis, including several putative glycosyltransferases involved in the synthesis of sialylated lipooligosaccharide inCampylobacter jejuni. In the present study,C. coliwas found to express lipooligosaccharide structures containing sialic acid and other nonulosonate acids. These findings have a strong impact in understandingC. coliecology, host-pathogen interaction, and pathogenesis.
Acute antidepressant effect of ayahuasca in juvenile non-human primate model of depression
Authors: Santos da Silva Flávia , Silva Erick Allan dos Santos , de Sousa Junior Geovan Menezes , Maia-de-Oliveira Joao Paulo , Rachetti Vanessa de Paula Soares , Barros de Araujo Draulio , Cordeiro de Sousa Maria Bernardete , Lobão Soares Bruno , Leite Galvão-Coelho Nicole 
Published: January 2018

ABSTRACTThe incidence of major depression in adolescents, aged between 15 to 18 years, reaches approximately 14%. Usually, this disorder presents a recurrent way, without remission of symptoms even after several pharmacological treatments, persisting through adult life. Due to the relatively low efficacy of commercially available antidepressant, new pharmacological therapies are under continuous exploration. Recent evidence suggests that classic psychedelics, such as ayahuasca, produce rapid and robust antidepressant effects in treatment-resistant depression patients. In this study, we evaluated the potential of antidepressant effects of ayahuasca in a juvenile model of depression in a non-human primate, common marmoset (Callithrix jacchus). The model induces depressive-like symptoms by chronic social isolation (60 days) and antidepressant effects monitoring included fecal cortisol, body weight, and behavioral parameters. The animals presented hypocortisolemia and the recovery of cortisol to baseline levels started already at 24h after the ingestion of ayahuasca, but not the vehicle. Moreover, in males, ayahuasca, and not the vehicle, reduced the scratching, a stereotypic behavior, and increased the feeding. Ayahuasca also improving body weight to baseline levels in male and female common marmosets. The behavioral response induced by ayahuasca shows long effect, lasting 14 days. Therefore, for this translational animal model of juvenile depression, it could be proposed that ayahuasca treatment presented more notable antidepressant effects than tricyclic antidepressant nortriptyline, investigated by our group, using this same protocol in an anterior study. Ayahuasca produced faster and more durable effect on reversion of physiological changes and depressive-like symptoms. Therefore, the results found for ayahuasca treatment corroborates in the validation of this substance as an effective antidepressant drug and encourages the return of studies with psychedelic drugs in the treatment of humor disorders, including adolescents with early-age depression.
Functional Gradients of the Cerebellum: A Fundamental Movement-To-Thought Principle
Authors: Guell Xavier , Schmahmann Jeremy D. , Gabrieli John D.E. , Ghosh Satrajit S. 
Published: January 2018

ABSTRACTA central principle for understanding the cerebral cortex is that macroscale anatomy reflects a functional hierarchy from primary to transmodal processing. In contrast, the central axis of motor and nonmotor macroscale organization in the cerebellum remains unknown. Here we applied diffusion map embedding to resting-state data from the Human Connectome Project dataset (n=1003), and show for the first time that cerebellar functional regions follow a gradual organization which progresses from primary (motor) to transmodal (DMN, task-unfocused) regions. A secondary axis extends from task-unfocused to task-focused processing. Further, these two principal gradients reveal functional properties of the well-established cerebellar double motor representation, and its relationship with the recently described triple nonmotor representation. These interpretations are further supported by data-driven clustering and cerebello-cerebral functional connectivity analyses. Importantly, these descriptions remain observable at the individual subject level. These findings, from an exceptionally large and high-quality dataset, provide new and fundamental insights into the functional organization of the human cerebellum, unmask new testable hypotheses for future studies, and yield an unprecedented tool for the topographical, macroscale interpretation of cerebellar findings.
Predicting protein targets for drug-like compounds using transcriptomics
Authors: Pabon Nicolas A. , Xia Yan , Estabrooks Samuel K. , Ye Zhaofeng , Herbrand Amanda K. , Süß Evelyn , Biondi Ricardo M. , Assimon Victoria A. , Gestwicki Jason E. , Brodsky Jeffrey L. , Camacho Carlos J. , Bar-Joseph Ziv 
Published: January 2018

AbstractThe development of an expanded chemical space for screening is an essential step in the challenge of identifying chemical probes for new, genomic-era protein targets. However, the difficulty of identifying targets for novel compounds leads to the prioritization of synthesis linked to known active scaffolds that bind familiar protein families, slowing the exploration of available chemical space. To change this paradigm, we validated a new pipeline capable of identifying compound-protein interactions even for compounds with no similarity to known drugs. Based on differential mRNA profiles from drug treatments and gene knockdowns across multiple cell types, we show that drugs cause gene regulatory network effects that correlate with those produced by silencing their target protein-coding gene. Applying supervised machine learning to exploit compound-knockdown signature correlations and enriching our predictions using an orthogonal structure-based screen, we achieved top-10/top-100 target prediction accuracies of 26%/41%, respectively, on a validation set 152 FDA-approved drugs and 3104 potential targets. We further predicted targets for 1680 compounds and validated a total of seven novel interactions with four difficult targets, including non-covalent modulators of HRAS and KRAS. We found that drug-target interactions manifest as gene expression correlations between drug treatment and both target gene knockdown and up/down-stream knockdowns. These correlations provide biologically relevant insight on the cell-level impact of disrupting protein interactions, highlighting the complex genetic phenotypes of drug treatments. Our pipeline can accelerate the identification and development of novel chemistries with potential to become drugs by screening for compound-target interactions in the full human interactome.
Study of the critical success factors of emblematic hotels through the analysis of content of online opinions
Authors: Fuentes-Medina M. Lilibeth , Hernández-Estárico Estefanía , Morini-Marrero Sandra 
Published: January 2018

Purpose
The purpose of this paper is to identify the critical success factors of emblematic hotels from the perspective of the guest, by analysing the direct activities that make up the value chain of these types of establishments.

Design/methodology/approach
The authors use the case study methodology to derive conclusions that contribute to the development of a theory about the success factors of emblematic hotels. The case selected is the Spanish Tourist Parador chain. The authors carried out over a period of two years a data mining analysis of the online comments posted by its guests.

Findings
The results indicate that the attributes of location and facilities are critical success factors expected a priori given the nature of the business of such establishments, based on the singular nature of the buildings. Another critical success factor is personnel, which seems to indicate that the Paradors support their business model by employing highly qualified staff, but give less attention to restaurant services or the room, according to guest perceptions.

Originality/value
The paper provides required evidence on the critical success factors of emblematic hotels adapting Porter’s value chain, for the tourism accommodation sector, through the analysis of direct value chain activities. In addition, the existing literature is broadened by taking a perspective scarcely studied, the guest perception of hotel establishments, online content posted by the user on the establishment’s website, rather than simply considering the traditional views of the experts/managers, through structures questionnaires. Besides, the results provide practical and useful implications for the managements of the emblematic hotels under study.
Unveiling the factors affecting final electricity consumption: does the regional component matter?
Authors: Borozan Djula , Pekanov Starcevic Dubravka 
Published: January 2018

PurposeThe purpose of this paper is to explore the developments in final electricity consumption, estimate the portions of changes that can be attributed to national, sectoral or regional factors, and to investigate determinants of the regional component (RC) in Croatia at the subnational level in the period 2001-2013.Design/methodology/approachIn the first stage, the dynamic shift-share method is used to decompose final electricity consumption, and then, in the second stage, the panel population-averaged logit model is conducted to find the main determinants of the extracted RC.FindingsThe results show that both the sectoral factor and the regional factor are responsible for an increase in electricity consumption over the period considered, whereby the regional specificities had a larger impact in general. Thereby, the most developed regions, including the tourism-oriented ones, exhibited the largest average increase in electricity consumption mainly due to positive effects of the regional-specific factors, while the negative effects of these factors were mainly responsible for low average rates of changes in electricity consumption in less developed regions.Practical implicationsThe results suggest that regional-specific energy conservation programs might be more effective in improving energy efficiency than the sector-oriented ones, as well as that socio-economic and contextual determinants matter when it comes to the probability of having a positive regional effect on the electricity consumption rate.Originality/valueThe paper investigated the determinants of the extracted RC which has not yet been addressed in the energy economics literature.