bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-specific transcriptomics reveal functional differences in maize floral development
Authors: Yang Hailong , Nukunya Kate , Ding Queying , Thompson Beth E. 
Published: May 2021

AbstractFlowers are produced by floral meristems, groups of stem cells that give rise to floral organs. In grasses, including the major cereal crops, flowers (florets) are contained in spikelets, which contain one to many florets, depending on the species. Importantly, not all grass florets are developmentally equivalent, and one or more florets are often sterile or abort in each spikelet. Members of the Andropogoneae tribe, including maize, produce spikelets with two florets; the upper and lower florets are usually dimorphic and the lower floret greatly reduced compared to the upper floret. In maize ears, early development appears identical in both florets but the lower floret ultimately aborts. To gain insight into the functional differences between florets of different fates, we used laser capture microdissection coupled with RNA-seq to globally examine gene expression in upper and lower floral meristems in maize. Differentially expressed genes were involved in hormone regulation, cell wall, sugar and energy homeostasis. Furthermore, cell wall modifications and sugar accumulation differed between the upper and lower florets. Finally, we identified a novel boundary domain between upper and lower florets, which we hypothesize is important for floral meristem activity. We propose a model in which growth is suppressed in the lower floret by limiting sugar availability and upregulating genes involved in growth repression. This growth repression module may also regulate floret fertility in other grasses and potentially be modulated to engineer more productive cereal crops.One sentence summaryFloret-specific differences in cell wall composition and sugar accumulation likely contribute to growth suppression in the lower floret of maize spikelets.
The SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia
Authors: Polyanskaya Sofya A. , Moreno Rosamaria Y. , Lu Bin , Feng Ruopeng , Yao Yu , Irani Seema , Klingbeil Olaf , Yang Zhaolin , Wei Yiliang , Demerdash Osama E. , Benjamin Lukas A. , Weiss Mitchell J. , Zhang Yan Jessie , Vakoc Christopher R. 
Published: May 2021

SummaryAcute myeloid leukemia (AML) cells rely on phospho-signaling pathways to gain unlimited proliferation potential. Here, we used domain-focused CRISPR screening to identify the nuclear phosphatase SCP4 as a dependency in AML, yet this enzyme is dispensable in normal hematopoietic progenitor cells. Using CRISPR exon scanning and gene complementation assays, we show that the catalytic function of SCP4 is essential in AML. Through mass spectrometry analysis of affinity-purified complexes, we identify the kinase paralogs STK35 and PDIK1L as binding partners and substrates of the SCP4 phosphatase domain. We show that STK35 and PDIK1L function catalytically and redundantly in the same pathway as SCP4 to maintain AML proliferation and to support amino acid biosynthesis and transport. We provide evidence that SCP4 regulates STK35/PDIK1L through two distinct mechanisms: catalytic removal of inhibitory phosphorylation and by promoting kinase stability. Our findings reveal a phosphatase-kinase signaling complex that supports the pathogenesis of AML.
Revealing RNA virus diversity and evolution in unicellular algae transcriptomes
Authors: Charon Justine , Murray Shauna , Holmes Edward C. 
Published: May 2021

AbstractRemarkably little is known about the diversity and evolution of RNA viruses in unicellular eukaryotes. We screened a total of 570 transcriptomes from the Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP) project that encompasses a wide diversity of microbial eukaryotes, including most major photosynthetic lineages (i.e. the microalgae). From this, we identified 30 new and divergent RNA virus species, occupying a range of phylogenetic positions within the overall diversity of RNA viruses. Approximately one-third of the newly described viruses comprised single-stranded positive-sense RNA viruses from the order Lenarviricota associated with fungi, plants and protists, while another third were related to the order Ghabrivirales, including members of the protist and fungi-associated Totiviridae. Other viral species showed sequence similarity to positive-sense RNA viruses from the algae-associated Marnaviridae, the double-stranded RNA Partitiviridae, as well as a single negative-sense RNA virus related to the Qinviridae. Importantly, we were able to identify divergent RNA viruses from distant host taxa, revealing the ancestry of these viral families and greatly extending our knowledge of the RNA viromes of microalgal cultures. Both the limited number of viruses detected per sample and the low sequence identity to known RNA viruses imply that additional microalgal viruses exist that could not be detected at the current sequencing depth or were too divergent to be identified using sequence similarity. Together, these results highlight the need for further investigation of algal-associated RNA viruses as well as the development of new tools to identify RNA viruses that exhibit very high levels of sequence divergence.
Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon
Authors: Tchetgna Huguette Simo , Yousseu Francine S. , Kamgang Basile , Tedjou Armel , McCall Philip J. , Wondji Charles 
Published: May 2021

AbstractAcute febrile patients presenting at hospitals in Douala, Cameroon between July and December 2020, were screened for dengue infections using RT-PCR on fragments of the 5’ and 3’ UTR genomic regions. In total, 12.8% (41/320) of cases examined were positive for dengue. Dengue virus 3 (DENV-3) was the most common serotype found (68.3%), followed by DENV-2 (19.5%) and DENV-1 (4.9%). Co-infections of DENV-3 and DENV-2 were found in 3 cases. Jaundice and headache were the most frequent clinical signs associated with infection and 176 cases (55%) were co-infections with malaria. Phylogenetic analysis of the envelope gene identified DENV-1 as belonging to genotype V, DENV-2 to genotype II and DENV-3 to genotype III. The simultaneous occurrence of three serotypes in Douala reveals dengue as a serious public health threat for Cameroon and highlights the need for further epidemiological studies in the major cities of this region.
Differences in progression by surgical specialty: a national cohort study
Authors: Hope Carla , Lund Jonathan , Griffiths Gareth , Humes David J 
Published: May 2021

AbstractThe aim of surgical training across the ten surgical specialties is to produce competent day one consultants. Progression through training is assessed by the Annual Review of Competency Progression (ARCP).ObjectiveThis study aimed to examine variation in ARCP outcomes within surgical training and identify differences between specialties.DesignA national cohort study using data from United Kingdom Medical Education Database (UKMED) was performed. ARCP outcome was the primary outcome measure. Multi-level ordinal regression analyses were performed, with ARCP outcomes nested within trainees.ParticipantsHigher surgical trainees (ST3-ST8) from 9 UK surgical specialties were included (vascular surgery was excluded due to insufficient data). All surgical trainees across the UK with an ARCP outcome between 2010 to 2017 were included.ResultsEight thousand two hundred and twenty trainees with an ARCP outcome awarded between 2010 and 2017 were included, comprising 31,788 ARCP outcomes. There was substantial variation in the proportion of non-standard outcomes recorded across specialties with general surgery trainees having the highest proportion of non-standard outcomes (22.5%) and urology trainees the fewest 12.4%. After adjustment, general surgery trainees were 1.3 times more likely to receive a non-standard ARCP outcome compared to trainees in T&O (OR 1.33 95%CI 1.21-1.45). Urology trainees were 36% less likely to receive a non-standard outcome compared to T&O trainees (OR 0.64 95%CI 0.54-0.75). Female trainees and older age were associated with non-standard outcomes (OR 1.11 95%CI 1.02-1.22; OR 1.04 95%CI 1.03-1.05).ConclusionThere is wide variation in the training outcome assessments across surgical specialties. General surgery has higher rates of non-standard outcomes compared to other surgical specialities. Across all specialities, female sex and older age were associated with non-standard outcomes.Article summaryStrengths and limitationsThis is the first study investigating factors affecting ARCP outcome across all surgical specialities.The major strength of the study is the large sample size comprising all higher surgical trainees between 2010 and 2017.Unlike previous studies this study uses data from reliable sources and is not dependent on survey data.Limitations include the inability to investigate the causes behind our findings due to the nature of the analysis.
Individual Level Differential Expression Analysis for Single Cell RNA-seq data
Authors: Zhang Mengqi , Liu Si , Miao Zhen , Han Fang , Gottardo Raphael , Sun Wei 
Published: May 2021

AbstractBulk RNA-seq data quantify the expression of a gene in an individual by one number (e.g., fragment count). In contrast, single cell RNA-seq (scRNA-seq) data provide much richer information: the distribution of gene expression across many cells. To assess differential expression across individuals using scRNA-seq data, a straightforward solution is to create “pseudo” bulk RNA-seq data by adding up the fragment counts of a gene across cells for each individual, and then apply methods designed for differential expression using bulk RNA-seq data. This pseudo-bulk solution reduces the distribution of gene expression across cells to a single number and thus loses a good amount of information. We propose to assess differential expression using the gene expression distribution measured by cell level data. We find denoising cell level data can substantially improve the power of this approach. We apply our method, named IDEAS (Individual level Differential Expression Analysis for scRNA-seq), to study the gene expression difference between autism subjects and controls. We find neurogranin-expressing neurons harbor a high proportion of differentially expressed genes, and ERBB signals in microglia are associated with autism.
Sugar units, not chilling units, control endodormancy duration in plants – potato tuber as a case study
Authors: Danieli Raz , Assouline Shmuel , Salam Bolaji Babajide , Teper-Bamnolker Paula , Belausov Eduard , Friedmann Yael , Granot David , Eshel Dani 
Published: May 2021

SummaryEndodormancy (ED) is a crucial stage in the life cycle of many perennial plants, regulated by genetic and environmental factors. Chilling units, growth regulators, and nutrient supply are considered inducers of ED release, but the mechanism governing ED duration is poorly understood. The potato tuber has been used as a model system to study metabolic processes associated with ED release. Cold-induced sweetening is a well-known response of the tuber to chilling. Here, we found that cold stress induces an increase in sugar units in association with plasmodesmatal closure in the dormant bud cells. Tuber sweetening was associated with shortened ED duration after cooling. Heat exposure also caused sugar unit accumulation followed by faster ED release. A logistic function was developed to predict ED duration based on sugar unit measurements. We discovered that ED release is better correlated with the accumulation of sugar units compared to chilling units. CRISPR/Cas9 knockout of the vacuolar invertase gene (StVInv) induced longer ED, but only in cultivars in which the mutation modified the level sugar units. Our results suggest that sugar units are better predictors of vegetative bud ED duration than chilling units.
Neural correlates of individual differences in aversion to risk and choice inconsistency
Authors: Jaquerod Manon E. , Lintas Alessandra , Gratton Gabriele , Low Kathy A. , Tobler Philippe N. , Villa Alessandro E. P. 
Published: May 2021

AbstractWhen making financial choices, most people prefer smaller but more certain gains to larger but more uncertain ones with the same expected value (risk aversion). However, attitudes toward risk may vary greatly also within individuals (choice inconsistency). To examine the brain dynamics implementing risky and inconsistent decisions, we recorded event-related brain potentials (ERPs) from 24 adults engaged in a task requiring choices between certain but smaller gains and uncertain but larger ones. Choice consistency and risk aversion were quantified for each individual. Participants were classified into three groups according to their attitude toward risk. Relative neutrality to risk was accompanied by a higher consistency across trials than risk aversion or proneness. Choice consistency was related to the amplitude of the positive ERP peaking near 200 ms after stimulus onset (P200), while risk aversion was related to modulation of the medial frontal negativity (MFN) and to the amplitude of a late positive potential (LPP). Late ERP activity was related to the modulation of value signals by risk levels and associated with individual differences in behavior. Overall, this study suggests that individual differences in attitude toward risk and choice consistency are associated with distinct brain dynamics.
Coordinated regulation of WNT/β-catenin, c-Met, and Integrin signalling pathways by miR-193b controls triple negative breast cancer metastatic traits
Authors: Giacomelli Chiara , Jung Janine , Wachter Astrid , Ibing Susanne , Will Rainer , Uhlmann Stefan , Mannsperger Heiko , Sahin Özgür , Yarden Yosef , Beißbarth Tim , Korf Ulrike , Körner Cindy , Wiemann Stefan 
Published: May 2021

ABSTRACTBackgroundTriple Negative Breast Cancer (TNBC) is the most aggressive subtype of Breast Cancer (BC). Treatment options for TNBC patients are limited and further insights into disease aetiology are needed to develop better therapeutic approaches. microRNAs’ ability to regulate multiple targets could hold a promising discovery approach to pathways relevant for TNBC aggressiveness. Thus, we address the role of miRNAs in controlling signalling pathways and phenotypes relevant to the biology of TNBC.MethodsTo identify miRNAs regulating WNT/β-catenin, c-Met, and integrin signalling pathways, we performed a high-throughput targeted proteomic approach, investigating the effect of 800 miRNAs on the expression of 62 proteins in the MDA-MB-231 TNBC cell line. We then developed a novel network analysis, Pathway Coregulatory (PC) score, to detect miRNAs regulating the three pathways. Usingin vitroassays for cell growth, migration, apoptosis, and stem-cell content, we validated the function of candidate miRNAs. Bioinformatic analyses using BC patients’ datasets were employed to assess expression of miRNAs as well as their pathological relevance in TNBC patients.ResultsWe identified six candidate miRNAs coordinately regulating the three signalling pathways. Quantifying cell growth of three TNBC cell lines upon miRNA gain-of-function experiments, we characterised miR-193b as a strong and consistent repressor of this phenotype. Importantly, the effects of miR-193b were stronger than chemical inhibition of the individual pathways. We further demonstrated that miR-193b induced apoptosis, repressed migration, and regulated stem-cell markers in MDA-MB-231 cells. Furthermore, miR-193b expression was the lowest in patients classified as TNBC or Basal compared to other subtypes when classified by PAM50 signatures. Gene Set Enrichment Analysis showed that miR-193b expression was significantly associated with reduced activity of of WNT/β-catenin and c-Met signalling pathways in TNBC patients.ConclusionsIntegrating miRNA-mediated effects and protein functions on networks, we show that miRNAs predominantly act in a coordinated fashion to activate or repress signalling pathways responsible for metastatic traits in TNBC. We further demonstrate that our top candidate, miR-193b, regulates these phenotypes to an extent stronger than individual pathway inhibition, thus proving that its effect on TNBC aggressiveness is mediated by repressing multiple interconnected pathways.
Three ParA dimers cooperatively assemble on type Ia partition promoters
Authors: Boudsocq François , Salhi Maya , Barbe Sophie , Bouet Jean-Yves 
Published: May 2021

ABSTRACTAccurate DNA segregation is essential for faithful inheritance of genetic material. In bacteria, this process is mainly ensured by a partition system (Par) composed of two proteins, ParA and ParB, and a centromere site. The auto-regulation of Par operon expression is important for efficient partitioning, and is primarily mediated by ParA for type Ia plasmid partition systems. For the plasmid F, four ParAF monomers were proposed to bind to four repeated sequences in the promoter region. By contrast, using quantitative surface plasmon resonance, we showed that three ParAF dimers bind to this region. We uncovered that one perfect inverted repeat (IR) motif, consisting of two hexamer sequences spaced by 28-bp, constitutes the primary ParAF DNA binding site. A similar but degenerated motif overlaps the former. ParAF binding to these motifs is well supported by biochemical and modeling analyses. In addition, molecular dynamics simulations predict that the winged-HTH domain displays high flexibility, which may favor the cooperative ParA binding to the promoter region. We propose that three ParAF dimers bind cooperatively to overlapping motifs thus covering the promoter region. A similar organization is found on both closely related and distant plasmid partition systems, suggesting that such promoter organization for auto-regulated Par operons is widespread and may have evolved from a common ancestor.
Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
Authors: Thapa Dibesh , Sousa Valente João de , Barrett Brentton , Argunhan Fulye , Lee Sheng Y. , Nikitochkina Sofya , Kodji Xenia , Brain Susan D. 
Published: May 2021

AbstractAgeing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor receptor in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.
Site-occupancy scheme in disordered Ca3RE2(BO3)4: a dependence on rare-earth (RE) ionic radius
Authors: Kosyl Katarzyna M. , Paszkowicz Wojciech , Minikayev Roman , Shekhovtsov Alexey N. , Kosmyna Miron B. , Chrunik Maciej , Fitch Andrew N. 
Published: May 2021

The structures of polycrystalline Ca3RE2(BO3)4(RE = La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Y; space groupPnma) orthoborates were determined using powder X-ray diffraction. Trends in the unit-cell dimensions and yet unreported trends in other structural properties (interatomic distances and the fractional occupation of three Ca/RE sites) for these compounds are demonstrated as a function of RE ionic radius. The unit-cell volume andaunit-cell parameter present a linear dependence, while thebandcunit-cell parameters change in a nonlinear manner. For the whole series, the RE atoms are present at all three cationic sites (labelled asM1,M2 andM3), but the fractional occupancies depend on the RE ionic radius. The small rare-earth atoms tend to enter mainly theM3 site; for the larger rare earths, the occupancy of this site decreases sharply. The occupancy of theM1 site by RE atoms is around 0.5 and tends to increase with increasing RE ionic radius. TheM2 site is the least preferentially occupied by RE ions, but the occupancy discernibly increases with rising radius as well. These findings are assembled with properties of isostructural strontium and barium borates, allowing prediction of occupancy schemes for not yet investigated compounds from theA3RE2(BO3)4(A= Ca, Ba, Sr).
Creating the digital citizen: students’ co-construction of meaning for global citizenship during online discussions
Authors: Myers John P. 
Published: May 2021

PurposeThis study examines whether online asynchronous discussion forums support student’s meaning-making about citizenship in a globalizing world. Citizenship is an increasingly contested identity for young people, yet they have few opportunities in traditional civic education to consider their own citizenship. Although online discussions are considered effective spaces for increasing dialogue and critical thinking between diverse students, there has been little research to understand how effective they are for helping students to construct new understandings of citizenship.Design/methodology/approachA content analysis approach was used to analyze and code 89 discussion board posts. The Interaction Analysis Model (IAM) coding scheme was used to describe and analyze the quality of knowledge construction that occurred across the posts focusing on different aspects of global citizenship.FindingsThe findings demonstrate that the discussion boards produced substantive talks about the meaning of citizenship that in some instances reached the level of new knowledge construction. The students considered different meanings for global citizenship and negotiated positions on key issues. However, the highest levels of knowledge construction were rarely reached.Practical implicationsA major implication is the need to organize and cue discussion boards to support knowledge construction in addition to fostering dialogue.Originality/valueThis study contributes to the role that technology can play in supporting students’ knowledge construction about global citizenship that go beyond the scripted meanings conveyed in civics classes.