bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single nucleotide substitution inTaHKT1;5-Dcontrols shoot Na+accumulation in bread wheat
Authors: Borjigin Chana , Schilling Rhiannon K. , Bose Jayakumar , Hrmova Maria , Qiu Jiaen , Wege Stefanie , Situmorang Apriadi , Brien Chris , Berger Bettina , Gilliham Matthew , Pearson Allison S. , Roy Stuart J. 
Published: January 2020

AbstractImproving salinity tolerance in the most widely cultivated cereal, bread wheat (Triticum aestivumL.), is essential to increase grain yields on saline agricultural lands. A Portuguese landrace, Mocho de Espiga Branca accumulates up to 6 folds greater leaf and sheath sodium (Na+) than two Australian cultivars, Gladius and Scout, under salt stress. Despite high leaf and sheath Na+concentrations, Mocho de Espiga Branca maintained similar salinity tolerance compared to Gladius and Scout. A naturally occurring single nucleotide substitution was identified in the gene encoding a major Na+transporter TaHKT1;5-D in Mocho de Espiga Branca, which resulted in a L190P amino acid residue variation. This variant prevents Mocho de Espiga Branca from retrieving Na+from the root xylem leading to a high shoot Na+concentration. The identification of the tissue tolerant Mocho de Espiga Branca will accelerate the development of more elite salt tolerant bread wheat cultivars.
High-throughput microCT scanning of small specimens: preparation, packing, parameters and post-processing
Authors: Hipsley Christy A. , Aguilar Rocio , Black Jay R. , Hocknull Scott A. 
Published: January 2020

AbstractHigh-resolution X-ray microcomputed tomography, or microCT (μCT), enables the digital imaging of whole objects in three dimensions. The power of μCT to visualise internal features without disarticulation makes it particularly valuable for the study of museum collections, which house millions of physical specimens documenting the spatio-temporal patterns of life. Despite its potential for comparative analyses, most μCT studies include limited numbers of museum specimens, due to the challenges of digitising numerous individuals within a project scope. Here we describe a method for high-throughput μCT scanning of hundreds of small (< 2 cm) specimens in a single container, followed by individual labelling and archival storage. We also explore the effects of various packing materials and multiple specimens per capsule to minimize sample movement that can degrade image quality, and hence μCT investment. We demonstrate this protocol on vertebrate fossils from Queensland Museum, Australia, as part of an effort to track community responses to climate change over evolutionary time. This system can be easily modified for other types of wet and dry material amenable to X-ray attenuation, including geological, botanical and zoological samples, providing greater access to large-scale phenotypic data and adding value to global collections.
Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD
Authors: Faiz A. , Pavlidis S. , Kuo C.S. , Rowe A. , Hiemstra P. S. , Timens W. , Berg M. , Wisman M. , Guo Y. , Djukanovic R. , Sterk P. J. , Nawijn M.C. , Adcock I. M. , Chung K. F. , van den Berge M. 
Published: January 2020

AbstractRationaleSevere asthma and COPD share common pathophysiologic traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures.ObjectiveWe examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity.MethodsUsing gene set variation analysis (GSVA), we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the GLUCOLD COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment.Measurements and main resultsBronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cell-specific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA.ConclusionsSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.
Allele mining unlocks the identification of RYMV resistance genes and alleles in African cultivated rice
Authors: Pidon Hélène , Chéron Sophie , Ghesquière Alain , Albar Laurence 
Published: January 2020

AbstractBackgroundRice yellow mosaic virus(RYMV) is a major rice pathogen in Africa. Three resistance genes, i.e.RYMV1,RYMV2andRYMV3,have been previously described.RYMV1encodes the translation initiation factor eIF(iso)4G-1 and the best candidate genes forRYMV2andRYMV3encode a homolog of anArabidopsisnucleoporin (CPR5) and a nucleotide-binding domain and leucine-rich repeat containing domain (NLR) protein, respectively. High resistance is very uncommon in Asian cultivated rice (Oryza sativa), with only two highly resistant accessions identified so far, but it is more frequent in African cultivated rice (Oryza glaberrima).ResultsHere we report the findings of a resistance survey in a reference collection of 268O. glaberrimaaccessions. A total of 40 resistant accessions were found, thus confirming the high frequency of resistance to RYMV in this species. We analysed the variability of resistance genes or candidate genes in this collection based on high-depth Illumina data or Sanger sequencing. Alleles previously shown to be associated with resistance were observed in 31 resistant accessions but not in any susceptible ones. Five original alleles with a frameshift or untimely stop codon in the candidate gene forRYMV2were also identified in resistant accessions. A genetic analysis revealed that these alleles, as well as T-DNA insertions in the candidate gene, were responsible of RYMV resistance. All 40 resistant accessions were ultimately linked to a validated or candidate resistance allele at one of the three resistance genes to RYMV.ConclusionThis study demonstrated that theRYMV2resistance gene is homologous to theArabidopsis CPR5gene and revealed five new resistance alleles at this locus. It also confirmed the close association between resistance and an amino-acid substitution in the leucine-rich repeat of the NLR candidate forRYMV3. We also provide an extensive overview of the genetic diversity of resistance to RYMV in theO. glaberrimaspecies, while underlining the contrasted pattern of diversity betweenO. glaberrimaandO. sativafor this trait. The different resistance genes and alleles will be instrumental in breeding varieties with sustainable field resistance to RYMV.
Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty acids
Authors: Chukaew Phatcharee , Leow Alex , Saengsawang Witchuda , Rasenick Mark M. 
Published: January 2020

AbstractWhile several therapeutic strategies exist for depression, most antidepressant drugs require several weeks before reaching full biochemical efficacy and remission is not entirely achieved in many patients. Therefore, biomarkers for depression and drug-response would help tailor treatment strategies. This study made use of banked human lymphoblast cell lines (LCLs) from normal and depressed subjects; the latter divided into remitters and non-remitters. Due to the fact that previous studies have shown effects on growth factors, cytokines and elements of the cAMP generating system as potential biomarkers for depression and antidepressant action, these were examined in LCLs. Initial gene and protein expression profiles for signaling cascades related to neuroendocrine and inflammatory functions differ among the three groups. Growth factor genes, includingVEGFAandBDNFwere significantly down-regulated in cells from depressed subjects. In addition, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to act as both antidepressants and anti-inflammatories, but the mechanisms for these effects are not established. Here we showed that n-3 PUFAs and escitalopram (selective serotonin reuptake inhibitors, SSRIs) treatment increased adenylyl cyclase (AC) andBDNFgene expression in LCLs. These data are consistent with clinical observations showing that n-3 PUFA and SSRI have antidepressant affects, which may be additive. Contrary to observations made in neuronal and glial cells, n-3 PUFA treatment attenuated cAMP accumulation in LCLs. However, while lymphoblasts show paradoxical responses to neurons and glia, patient-derived lymphoblasts appear to carry potential depression biomarkers making them an important tool for studying precision medicine in depressive patients. Furthermore, these data validate usefulness of n-3 PUFAs in treatment for depression.
C. elegansestablishes germline versus soma by balancing inherited histone methylation
Authors: Carpenter Brandon S. , Lee Teresa W. , Plott Caroline F. , Brockett Jovan S. , Myrick Dexter A. , Katz David J. 
Published: January 2020

ABSTRACTEmbryos undergo extensive reprogramming at fertilization to prevent the inappropriate inheritance of histone methylation. InC. elegans,this reprogramming is mediated by the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2. In contrast to this reprogramming, the H3K36 methyltransferase, MES-4, maintains H3K36me2/3 at germline genes between generations to help re-establish the germline. To determine whether the MES-4 germline inheritance system antagonizesspr-5; met-2reprogramming, we examined the interaction between these two systems. We find that the developmental delay ofspr-5; met-2mutant progeny is associated with ectopic H3K36me2/3 and the ectopic expression of MES-4 targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that the MES-4 inheritance system prevents critical germline genes from being repressed by maternalspr-5; met-2reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.
The self-face captures attention without consciousness: evidence from the N2pc ERP component analysis
Authors: Bola Michał , Paź Marta , Doradzińska Łucja , Nowicka Anna 
Published: January 2020

AbstractIt is well established that stimuli representing or associated with ourselves, like our own name or an image of our own face, benefit from preferential processing. However, two key questions concerning the self-prioritization mechanism remain to be addressed. First, does it operate in an automatic manner during the early processing, or rather in a more controlled fashion at later processing stages? Second, is it specific to the self-related stimuli, or can it be activated also by other stimuli that are familiar or salient? We conducted a dot-probe experiment to investigate the mechanism behind attentional prioritization of the selfface image and to tackle both questions. The former, by employing a backwards masking procedure to isolate the early and preconscious processing stages. The latter, by investigating whether a face that becomes visually familiar due to repeated presentations is able to capture attention in a similar manner as the self-face. Analysis of the N2pc ERP component revealed that the self-face image automatically captures attention, both when processed consciously and unconsciously. In contrast, the visually familiar face did not attract attention, neither in the conscious, nor in the unconscious condition. We conclude that the selfprioritization mechanism is early and automatic, and is not triggered by a mere visual familiarity. More generally, our results provide further evidence for efficient unconscious processing of faces, and for a dissociation between attention and consciousness.
Substrate Channelingviaa Transient Protein-Protein Complex: The case of D-Glyceraldehyde-3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase
Authors: Svedružić Željko M. , Odorčić Ivica , Chang Christopher H. , Svedružić Draženka 
Published: January 2020

AbstractBackgroundD-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and L-lactate dehydrogenase (LDH) can form a complex that can regulate the major metabolic pathways, however, the exact mechanism remains unknown. We analyzed a possibility of NADH-channeling from GAPDH-NADH complex to LDH isozymes using enzymes from different cells.ResultsEnzyme-kinetics and NADH-binding studies showed that LDH can use GAPDH-NADH complex as a substrate. LDH activity with GAPDH-NADH complex was challenged with anti-LDH antibodies to show that the channeled and the diffusive reactions always take place in parallel. The channeling path is dominant only in assays with limiting free-NADH concertation that mimic cytosolic conditions. Analytical ultracentrifugation showed that the channeling does not require a high affinity complex. Molecular dynamics calculations and protein-protein interaction studies showed that LDH and GAPDH can form a leaky channeling complex only at subsaturating NADH concentrations. The interaction sites are conserved between LDH isozymes from heart and muscle, and between GAPDH molecules from rabbit and yeast cells. Positive electric fields between the NAD(H) binding sites on LDH and GAPDH tetramers, showed that NAD(H)-channeling within the LDH-GAPDH complex, can be an extension of NAD(H)-channeling between the adjacent subunits in each tetramer.ConclusionsIn the case of a transient (GAPDH-NADH)-LDH complex, the relative contribution from the channeled and the diffusive paths depends on the overlap betweenoff-rates for the transient (GAPDH-NADH)-LDH complex andoff-rates for the GAPDH-NADH complex. Molecular evolution or metabolic engineering protocols can exploit substrate channeling for metabolic flux control by fine-tuning substrate-binding affinity for the key enzymes in the competing reaction paths.Highlights- Substrate channeling molecular mechanism can regulate energy production and aerobic and anaerobic metabolism in cells- LDH and GAPDH can form a channeling complex only at sub-saturating NADH concentration- Channeled and diffusive paths always compete and take place in parallel- NADH channeling does not require a high-affinity complex- NADH channeling within GAPDH-LDH complex is an extension of NAD(H) channeling within each tetramer- Allosteric modulation of NADH binding affinity in GAPDH tetramer can regulate NAD(H) channeling
N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells
Authors: Yu Jiang-Zhou , Wang Jennifer , Sheridan Steven D. , Perlis Roy H. , Rasenick Mark M. 
Published: January 2020

AbstractEvidence from epidemiological and laboratory studies, as well as randomized placebo-controlled trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs potential therapeutic properties remain unknown. There are suggestions in the literature that glial hypofunction is associated with depressive symptoms and that antidepressants may normalize glial function. In this study, iPSC-derived neuronal stem cell lines were generated from individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and stearic acid (SA). During astrocyte differentiation, we found that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and GDNF production were increased in the astrocytes derived from patients subsequent to n-3 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n- 3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of some antidepressants by increasing production of neurotrophic factors. The CREB-dependence and cAMP independence of this process suggests a manner in which n-3 PUFA could augment antidepressant effects. These data also suggest a role for astrocytes in both MDD and antidepressant action.
CIRFESS: An interactive resource for querying the set of theoretically detectable peptides for cell surface and extracellular enrichment proteomic studies
Authors: Waas Matthew , Littrell Jack , Gundry Rebekah L. 
Published: January 2020

AbstractCell surface transmembrane, extracellular, and secreted proteins are high value targets for immunophenotyping, drug development, and studies related to intercellular communication in health and disease. As the number of specific and validated affinity reagents that target this subproteome are limited, mass spectrometry (MS)-based approaches will continue to play a critical role in enabling discovery and quantitation of these molecules. Given the technical considerations that make MS-based cell surface proteome studies uniquely challenging, it can be difficult to select an appropriate experimental approach. To this end, we have integrated multiple prediction strategies and annotations into a single online resource,CompiledInteractiveResourceforExtracellular andSurfaceStudies (CIRFESS). CIRFESS enables rapid interrogation of the human proteome to reveal the cell surface proteome theoretically detectable by current approaches and highlights where current prediction strategies provide concordant and discordant information. We applied CIRFESS to identify the percentage of various subsets of the proteome which are expected to be captured by targeted enrichment strategies, including two established methods and one that is possible but not yet demonstrated. These results will inform the selection of available proteomic strategies and development of new strategies to enhance coverage of the cell surface and extracellular proteome. CIRFESS is available atwww.cellsurfer.net/cirfess.
RBMS1 suppresses colon cancer metastasis through targeted stabilization of its mRNA regulon
Authors: Yu Johnny , Culbertson Bruce , Asgharian Hosseinali , Navickas Albertas , Fish Lisa , Olegario John Paolo , Hänisch Benjamin , Weinberg Ethan M , Dienstmann Rodrigo , Warren Robert S , Goodarzi Hani 
Published: January 2020

AbstractBroad dysregulation of gene expression control is a hallmark of cancer progression. Identifying the underlying master regulators that drive pathological gene expression is a key challenge in precision oncology. Here, we have developed a network analytical framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression. We observed that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression blunts metastatic liver colonization. We have found that RBMS1 functions as a post-transcriptional regulator of RNA stability by directly binding and stabilizing ~80 target mRNAs. Measurements in more than 180 clinical samples as well as survival analyses in publicly available datasets, have shown that RBMS1 silencing and the subsequent downregulation of its targets are strongly associated with disease progression and poor survival in colon cancer patients. Together, our findings establish a role for RBMS1 as a previously unknown regulator of RNA stability and as a suppressor of colon cancer metastasis with clinical utility for risk stratification of patients.SignificanceBy applying a new analytical approach to transcriptomic data from clinical samples and models of colon cancer progression, we have uncovered RBMS1 as a suppressor of metastasis and as a post-transcriptional regulator of RNA stability. Notably, RBMS1 silencing and downregulation of its targets are negatively associated with patient survival.
p.E152K-STIM1 mutation deregulates Ca2+signaling contributing to chronic pancreatitis
Authors: Burgos Miguel , Philippe Reginald , Antigny Fabrice , Buscaglia Paul , Masson Emmanuelle , Mukherjee Sreya , Dubar Pauline , Le Maréchal Cédric , Campeotto Florence , Lebonvallet Nicolas , Frieden Maud , Llopis Juan , Domingo Beatriz , Stathopulos Peter B. , Ikura Mitsuhiko , Brooks Wesley , Guida Wayne , Chen Jian-Min , Ferec Claude , Capiod Thierry , Mignen Olivier 
Published: January 2020

ABSTRACTSince deregulation of intracellular Ca2+can lead to intracellular trypsin activation and STIM1 (stromal interaction molecule-1) protein is the main regulator of Ca2+homeostasis in pancreatic acinar cells, we explored the Ca2+signaling in 37 STIM1 variants found in three pancreatitis patient cohorts. Extensive functional analysis of one particular variant, p.E152K, identified in three patients, provided a plausible link between dysregulated Ca2+signaling within pancreatic acinar cells and chronic pancreatitis susceptibility. Specifically, p.E152K, located within the STIM1 EF-hand and sterile α-motif domain, increased the release of Ca2+from the endoplasmic reticulum in patient-derived fibroblasts and transfected HEK293T cells. This event was mediated by altered STIM1-sarco/endoplasmic reticulum calcium transport ATPase (SERCA) interactions and enhanced SERCA pump activity leading to increased Store Operated Calcium Entry (SOCE). In the pancreatic AR42J cells expressing the p.E152K variant, Ca2+-signaling perturbations correlated with defects in trypsin activation and secretion, and increased cytotoxicity after cholecystokinin stimulation.Summary statementp.E152K-STIM1 variant found in pancreatitis patients leads to intracellular changes in calcium homeostasis through SERCA interaction, enabling intracellular trypsin activation and pancreatic acinar cell death.