bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and Genomic Resources to Study Natural Variation inBrassica rapa
Authors: Lou Ping , Woody Scott , Greenham Kathleen , VanBuren Robert , Colle Marivi , Edger Patrick P. , Sartor Ryan , Zheng Yakun , Levendoski Nathan , Lim Jan , So Calvin , Stoveken Brian , Woody Timothy , Zhao Jianjun , Shen Shuxing , Amasino Richard M. , McClung C. Robertson 
Published: June 2020

ABSTRACTThe globally important cropBrassica rapa, a close relative of Arabidopsis, is an excellent system for modeling our current knowledge of plant growth on a morphologically diverse crop. The long history ofB. rapadomestication across Asia and Europe provides a unique collection of locally adapted varieties that span large climatic regions with various abiotic and biotic stress tolerance traits. This diverse gene pool provides a rich source of targets with the potential for manipulation towards the enhancement of productivity of crops both within and outside the Brassicaceae. To expand the genetic resources available to study natural variation inB. rapa, we constructed an Advanced Intercross Recombinant Inbred (AI-RIL) population usingB. rapasubsp.trilocularis(Yellow Sarson) R500 and theB. rapasubsp.parachinensis(Cai Xin) variety L58. Our current understanding of genomic structure variation across crops suggests that a single reference genome is insufficient for capturing the genetic diversity within a species. To complement this AI-RIL population and current and futureB. rapagenomic resources, we generated ade novogenome assembly of theB. rapasubsp.trilocularis(Yellow Sarson) variety R500, the maternal parent of the AI-RIL population. The genetic map for the R500 x L58 population generated using thisde novogenome was used to map QTL for seed coat color and revealed the improved mapping resolution afforded by this new assembly.
IMIX: A multivariate mixture model approach to integrative analysis of multiple types of omics data
Authors: Wang Ziqiao , Wei Peng 
Published: June 2020

AbstractMotivationIntegrative genomic analysis is a powerful tool to study the biological mechanisms underlying a complex disease or trait across multiplatform high-dimensional data, such as DNA methylation, copy number variation (CNV), and gene expression. It is common to perform large-scale genome-wide association analysis of an outcome for each data type separately and combine the resultsad hoc, leading to loss of statistical power and uncontrolled overall false discovery rate (FDR).ResultsWe propose a multivariate mixture model framework (IMIX) that integrates multiple types of genomic data and allows examining and relaxing the commonly adopted conditional independence assumption. We investigate across-data-type FDR control in IMIX, and show the gain in lower misclassification rates at controlled over-all FDR compared with established individual data type analysis strategies, such as Benjamini-Hochberg FDR control, the q-value, and the local FDR control by extensive simulations. IMIX features statistically-principled model selection, FDR control, and computational efficiency. Applications to the Cancer Genome Atlas (TCGA) data provide novel multi-omic insights into the luminal/basal subtyping of bladder cancer and the prognosis of pancreatic cancer.Availability and implementationWe have implemented our method in R package “IMIX” with instructions and examples available athttps://github.com/ziqiaow/IMIX.
Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruziactivity
Authors: Valera-Vera Edward A. , Reigada Chantal , Sayé Melisa , Digirolamo Fabio A. , Miranda Mariana R. , Pereira Claudio A. 
Published: June 2020

ABSTRACTTrypanosoma cruziis the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruziarginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50= 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC5057-fold lower than benznidazole, the drug currently used for treating Chagas disease.
The proteomic landscape of centromeric chromatin reveals an essential role for the Ctf19CCANcomplex in meiotic kinetochore assembly
Authors: Borek Weronika E. , Vincenten Nadine , Duro Eris , Makrantoni Vasso , Spanos Christos , Sarangapani Krishna K. , Alves Flavia de Lima , Kelly David A. , Asbury Charles L. , Rappsilber Juri , Marston Adele L. 
Published: June 2020

ABSTRACTKinetochores direct chromosome segregation in mitosis and meiosis. Faithful gamete formation through meiosis requires that kinetochores take on new functions that impact homolog pairing, recombination and the orientation of kinetochore attachment to microtubules in meiosis I. Using an unbiased proteomics pipeline, we determined the composition of centromeric chromatin and kinetochores at distinct cell-cycle stages, revealing extensive reorganisation of kinetochores during meiosis. The data uncover a network of meiotic chromosome axis and recombination proteins that replace the microtubule-binding outer kinetochore sub-complexes during meiotic prophase. We show that this kinetochore remodelling in meiosis requires the Ctf19cCCANinner kinetochore complex. Through functional analyses, we identify a Ctf19cCCAN-dependent kinetochore assembly pathway that is dispensable for mitotic growth, but becomes critical upon meiotic entry. Therefore, extensive kinetochore remodelling and a distinct assembly pathway direct the specialization of meiotic kinetochores for successful gametogenesis.
Photoacoustic imaging resolves species-specific differences in haemoglobin concentration and oxygenation
Authors: Hacker Lina , Brunker Joanna , St. John Smith Ewan , Quiros-Gonzalez Isabel , Bohndiek Sarah E. 
Published: June 2020

AbstractIntroductionPhotoacoustic imaging (PAI) enables the detection of blood haemoglobin (HB) concentration and oxygenation (SO2) with high contrast and resolution. To date, the relationship between photoacoustically determined total Haemoglobin (THbMSOT) and oxygen saturation (SO2) biomarkers and the underlying biochemical blood parameters has yet to be established. We sought to explore these relationships in a species-specific manner.MethodsExperiments were performedin vitrousing tissue-mimicking agar phantoms. Blood was extracted from mouse, rat, human and naked mole-rat (Heterocephalus glaber), anticoagulated in EDTA and measured within 48 hours. THbMSOTand SO2MSOTwere measured using a commercial photoacoustic tomography system (InVision 128, iThera Medical GmBH). Biochemical blood parameters such as haemoglobin concentration (HB, g/dL), haematocrit (HCT, %) and red blood cell count (RBC, μL-1) were assessed using a haematology analyser (Mythic 18 Vet, Woodley Equipment).ResultsA significant correlation was observed between THbMSOTand biochemical HB, HCT and RBC in mouse and rat blood. Moreover, PAI accurately recapitulated inter-species variations in HB and HCT between mouse and rat blood and resolved differences in the oxygen dissociation curves between human, mouse and rat. With these validation data in hand, we applied PAI to studies of blood obtained from naked mole-rats and could confirm the high oxygen affinity of this species in comparison to other rodents of similar size.ConclusionIn summary, our results demonstrate the high sensitivity of photoacoustically determined biomarkers towards species-specific variationsin vitro.
Ecologically relevant thermal fluctuations enhance offspring fitness: biological and methodological implications for studies of thermal developmental plasticity
Authors: Hall Joshua M. , Warner Daniel A. 
Published: June 2020

ABSTRACTNatural thermal environments are notably complex and challenging to mimic in controlled studies. Consequently, our understanding of the ecological relevance and underlying mechanisms of organismal responses to thermal environments is often limited. For example, studies of thermal developmental plasticity have provided key insights into the ecological consequences of temperature variation, but most laboratory studies use treatments that do not reflect natural thermal regimes. While controlling other important factors, we compared the effects of naturally fluctuating temperatures to commonly used laboratory regimes on development of lizard embryos and offspring phenotypes and survival. We incubated eggs in 4 treatments – 3 that followed procedures commonly used in the literature, and one that precisely mimicked naturally fluctuating nest temperatures. To explore context-dependent effects, we replicated these treatments across two seasonal regimes: relatively cool temperatures from nests constructed early in the season and warm temperatures from late-season nests. We show that natural thermal fluctuations have a relatively small effect on developmental variables but enhance hatchling performance and survival at cooler temperatures. Thus, natural thermal fluctuations are important for successful development and simpler approximations (e.g. repeated sine waves, constant temperatures) may poorly reflect natural systems under some conditions. Thus, the benefits of precisely replicating real-world temperatures in controlled studies may outweigh logistical costs. Although patterns might vary according to study system and research goals, our methodological approach demonstrates the importance of incorporating natural variation into controlled studies and provides biologists interested in thermal ecology with a framework for validating the effectiveness of commonly used methods.
The role of Ca2+and protein scaffolding in the formation in nature’s water oxidizing complex
Authors: Avramov Anton P. , Hwang Hong J. , Burnap Robert L. 
Published: June 2020

AbstractThe photosystem II (PSII) complex catalyzing the H2O-oxidation reaction of photosynthesis is highly prone to photodamage. Nature has evolved synthesis and repair mechanisms that include the photooxidative self-assembly, termed photoactivation, of the Mn4CaO5metal cluster responsible for H2O-oxidation. Assembly is a multi-step light-driven process that proceeds with low quantum yield, involves a critical molecular rearrangement between light-activated steps, and is prone to photoinactivation and mis-assembly. A sensitive polarographic technique was used to track the assembly process under flash illumination as a function of the constituent Mn2+and Ca2+ions in genetically engineered samples to elucidate the action of Ca2+and peripheral proteins. We show that the protein scaffolding that organizes this process is modulated allosterically by the assembly protein Psb27, which together with Ca2+, stabilizes the intermediates of photoactivation, a feature especially evident at long intervals between photoactivating flashes. Besides stabilizing intermediates, the Ca2+ion is also critical to prevent photoinactivation due to inappropriate binding of Mn2+. Overexpression of Psb27, deletion of extrinsic protein PsbO, and excess Ca2+characteristically modify these processes and retard the dark rearrangement. The results suggest the involvement of three metal binding sites, two Mn and one Ca with occupation of the Ca site by Ca2+critical for the suppression of inactivation and the long-observed competition between Mn2+and Ca2+occurring at the second Mn site necessary for trapping the first stable assembly intermediates.Significance StatementThe oxidation of water by the photosystem II is the foundation of bioproductivity on Earth and represents a blueprint for sustainable, carbon neutral technologies. Water oxidation is catalyzed by a metal cluster containing of 4 Mn and 1 Ca atoms linked via oxo bridges. The initial assembly is a complex sequential reaction harnessing the photochemical reaction center to photooxidatively incorporate Mn2+and Ca2+ions into the catalytic unit embedded in the protein matrix. This photoassembly is crucial for both de novo biosynthesis and as part of the ‘self-healing’ mechanism to cope with incessant photodamage that photosynthetic organisms experience. The results have implications for the natural mechanism as well as the highly desirable biomimetic devices currently envisioned for solar energy production.
Opposing directions of stage-specific body length change in a close relative ofC. elegans
Authors: Hammerschmith Eric W. , Woodruff Gavin C. , Phillips Patrick C. 
Published: June 2020

AbstractBackgroundBody size is a fundamental organismal trait. However, as body size and ecological contexts change across developmental time, evolutionary divergence may cause unexpected patterns of body size diversity among developmental stages. This may be particularly evident in polyphenic developmental stages specialized for dispersal. The dauer larva is such a stage in nematodes, andCaenorhabditisspecies disperse by traveling on invertebrate carriers. Here, we describe the morphology of the dispersal dauer larva of the nematodeCaenorhabditis inopinata, whose adults can grow to be nearly twice as long as its close relative, the model organismC. elegans.ResultsWe find that theC. inopinatadauer larva is shorter and fatter than those of its close relativesC. elegans, C. briggsae, andC. tropicalis, despite its much longer adult stage. Additionally, manyC. inopinatadauer larvae were ensheathed, an apparent novelty in this lineage reminiscent of the infective juveniles of parasitic nematodes. We also found abundant variation in dauer formation frequency among twenty-four wild isolates ofC. inopinata, with many strains unable to produce dauer larvae under laboratory conditions.ConclusionMostCaenorhabditisspecies thrive on rotting plants and disperse on snails, slugs, or isopods (among others) whereasC. inopinatais ecologically divergent and thrives in freshFicus septicafigs and disperses on their pollinating wasps. These wasps are at least an order of magnitude smaller in length than the vectors of otherCaenorhabditisspecies. While there is some unknown factor of the fig environment that promotes elongated body size inC. inopinataadults, the smaller size of its fig wasp carrier may be driving the reduced body length of its dauer larva. Thus ecological divergence across multiple developmental stages can promote unexpected and opposing changes in body size within a single species.
De novo deletions and duplications at recombination hotspots in mouse germlines
Authors: Lukaszewicz Agnieszka , Lange Julian , Keeney Scott , Jasin Maria 
Published: June 2020

SummaryNumerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here we uncover a new type of mutational event in which deletions form via joining of ends from two closely spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution.
Office design processes, strategizing and time intermingling: an agenda to shape spaces and minds in public accounting firms
Authors: Picard Claire-France , Durocher Sylvain , Gendron Yves 
Published: June 2020

PurposeThis paper investigates the strategic processes surrounding the development, in accounting firms, of office (re)design projects and their overarching objectives.Design/methodology/approachThe authors’ investigation relies on a series of interviews with individuals from different accounting firms involved in the decision process related to office (re)design projects. A triangular template made up of strategy, space and time informs the analysis, which the authors complement by relying on a strategy-as-practice integrated framework.FindingsThe authors found that accounting firm office (re)design projects are characterized by a strategic spatial agenda that aims to define and create present organizational time, in ways that embed a particular vision of the future. The analysis brings to light the interrelationships between strategy practitioners, strategy practices and strategic work through which the future is actualized. Office design processes involve not only the physical transformation of office space; they also promote a prominent agenda to modify, in the long run, office members' minds. Hence, office (re)design processes may be conceived of as a significant device in the socialization of accounting practitioners.Research limitations/implicationsThis study underscores that spatial strategizing constitutes a major device through which the future is brought into the present. As such, the analysis provides insights not only into the processes through which space transformations take place, but also into their underlying agenda. The latter promotes the advent, in present time, of the organic office of the future.Practical implicationsThis analysis brings to the fore a concrete illustration of how the strategy-space-time triangle operates in organizational life. The authors underline the key role played by strategists in charge of designing the office of the future.Originality/valueThis study extends the burgeoning literature whose analytical gaze is informed by the strategy, space, and time triangle.
Mitigating and adapting to climate change: attitudinal and behavioural challenges in South Asia
Authors: Alvi Shahzad , Khayyam Umer 
Published: June 2020

Purpose
This study aims to examine peoples’ perception of climate change. It assessed their attitude, behavioural motivation for mitigating and adapting to climate change in the two capital cities of South Asia: Islamabad in Pakistan and Dhaka in Bangladesh.

Design/methodology/approach
This study used the quantitative research technique based on responses of 800 close-ended questions embedded in a close-ended questionnaire, which were filled-out from randomly selected sample of respondents. The primary data was analysed and presented through tabulation. For binary dependent variables, the standardised logistic coefficients were projected for more reliable estimates.

Findings
The findings reveal that the population of both capital cities have a low personal perception of climate change. Also, the dwellers of both cities have a low level of motivation to take mitigative and adaptive measures against climatic hazards. The results of the logistic regression model further indicate that the people who believe that climate change is a threat to their lives are more likely to adopt mitigative and adaptive strategies. This mostly applies to the people with a relatively higher income and education level.

Research limitations/implications
This study implies to create awareness and sensitise the local community in both the capitals and beyond through information dissemination. Further, the availability of toolkits to handle emergencies remains imperative in registering attitudinal and behavioural changes to reduce the impacts of climate variability in poor localities.

Originality/value
This research study analysed the link between climate change mitigation and energy conservation from the societal attributes of perception, motivation, attitude and behaviour, which remains essential for community-based mitigation against climatic hazards.
Determinants of crowdfunding intention in a developing economy: ex-ante evidence from Bangladesh
Authors: Munim Ziaul Haque , Shneor Rotem , Adewumi Olugbenga Michael , Shakil Mohammad Hassan 
Published: June 2020

PurposeSME funding gaps in developing economies are substantial. Crowdfunding is an innovative way to raise funds that may be part of the solution for closing such gaps. The purpose of this study is to investigate the determinants of crowdfunding contribution intentions in the context of a developing country –Bangladesh.Design/methodology/approachThe authors collect data by using a structured questionnaire distributed through Facebook. The analysis is based on data collected from 252 valid responses and uses the ordered probit regression for estimation. For robustness, the authors also estimate the hypothesized model using ordered logistic regression and OLS regression finding identical results.FindingsThe authors find that liking the campaign idea and positive media coverage of a crowdfunding campaign have a positive association with crowdfunding contribution intention. Surprisingly, personal relations, others' recommendation and the location of the campaign's owner were not significantly associated with crowdfunding contribution intention in our study. Moreover, respondents' location in Bangladesh (vs. abroad) and their age are positively associated with contribution intention, while education is negatively associated with intention.Originality/valueEarlier studies focused on the determinants of ex post crowdfunding intentions in developed and more mature crowdfunding markets. The authors contribute by examiningex antecrowdfunding contribution intentions in the developing economy of Bangladesh, which is at the market's inception stage.