bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Distribution of Enset Pests and Pathogens and a Genomic Survey of Enset Xanthomonas Wilt
Authors: Yemataw Zerihun , Borrell James S. , Biswas Manosh Kumar , White Oliver , Mengesha Wendawek , Muzemil Sadik , Darbar Jaypal N. , Ondo Ian , Harrison Pat J.S. Heslop , Blomme Guy , Wilkin Paul 
Published: June 2020

AbstractMapping the distribution of crop pests and pathogens is essential to safeguard food security and sustainable livelihoods. However, these data are unavailable for many neglected and underutilised crops, particularly in developing countries. In Ethiopia, the world’s largest historic recipient of food aid, the indigenous banana relative enset (Ensete ventricosum) is threatened by multiple pests and pathogens whilst providing the staple starch source for 20 million people. Foremost among these isXanthomonasWilt of enset (EXW), caused byXanthomonas vasicolapv.musacearum(Xvm), a globally important disease of bananas (Musasp.) that likely originated in enset. Here we collate 1069 farm surveys to map the distribution and relative prevalence of enset pests and pathogens across the entire enset growing region. We find that EXW is the most frequently encountered pathogen, and that farmers consistently ranked EXW as the most significant constraint on enset agriculture. Our surveys also showed that corm rot, and the pests root mealybug, mole rat and porcupine are all virtually ubiquitous. Finally, we apply genotyping-by-sequencing to the detection ofXvmand demonstrate that it is present even in asymptomatic domesticated and wild enset samples, suggesting that management of plants displaying symptoms alone may not be sufficient to reduce disease transmission. Holistic understanding of pests and pathogen distributions in enset may have significant benefits for both food security in Ethiopia, and preventing proliferation in related crops such as banana across central and east Africa.
Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche
Authors: Martín-Alonso Mara , Lindholm Håvard T. , Iqbal Sharif , Vornewald Pia , Hoel Sigrid , Damen Mirjam J. , Altelaar A.F.Maarten , Katajisto Pekka , Arroyo Alicia G. , Oudhoff Menno J. 
Published: June 2020

SUMMARYSmooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.
The failure of B cells to induce non-canonicalMYD88splice variants correlates with lymphomagenesis via sustained NF-κB signaling
Authors: Gloria Yamel Cardona , Bernhart Stephan H. , Fillinger Sven , Wolz Olaf-Oliver , Dickhöfer Sabine , Admard Jakob , Ossowski Stephan , Nahnsen Sven , Siebert Reiner , Weber Alexander N.R. 
Published: June 2020

AbstractGain-of-function mutations of the TLR adaptor and oncoprotein MyD88 drive B cell lymphomagenesis via sustained NF-κB activation. In myeloid cells, sustained TLR activation and NF-κB activation lead to the induction of inhibitoryMYD88splice variants that restrain prolonged NF-κB activation. We therefore sought to investigate whether such a negative feedback loop exists in B cells. AnalyzingMYD88splice variants in normal B cells and different primary B cell malignancies, we observed thatMYD88splice variants in transformed B cells are dominated by the canonical, strongly NF-κB-activating isoform ofMYD88and contain at least three novel, so far uncharacterized signaling-competent splice isoforms. TLR stimulation in B cells unexpectedly reinforces splicing of NF-κB-promoting, canonical isoforms rather than the ‘MyD88s’, a negative regulatory isoform that is typically induced by TLRs in myeloid cells. This suggests that an essential negative feedback loop restricting TLR signaling in myeloid cells at the level of alternative splicing, is missing in B cells, rendering B cells vulnerable to sustained NF-κB activation and eventual lymphomagenesis. Our results uncoverMYD88alternative splicing as an unappreciated promoter of B cell lymphomagenesis and provide a rationale why oncogenicMYD88mutations are exclusively found in B cells.
Enterococcal PrgA extends far outside the cell and provides surface exclusion to protect against unwanted conjugation
Authors: Schmitt Andreas , Hirt Helmut , Järvå Michael A. , Sun Wei-Sheng , Beek Josy ter , Dunny Gary M. , Berntsson Ronnie P-A 
Published: June 2020

AbstractHorizontal gene transfer between Gram-positive bacteria leads to a rapid spread of virulence factors and antibiotic resistance. This transfer is often facilitated via Type 4 Secretion Systems (T4SS), which frequently are encoded on conjugative plasmids. However, donor cells that already contain a particular conjugative plasmid resist acquisition of a 2ndcopy of said plasmid. They utilize different mechanisms, including surface exclusion for this purpose.Enterococcus faecalisPrgA, encoded by the conjugative plasmid pCF10, is a surface protein that has been implicated to play a role in both virulence and surface exclusion, but the mechanism by which this is achieved has not been fully explained. Here, we report the structure of full-length PrgA, which shows that PrgA protrudes far out from the cell wall (approximately 40 nm), where it presents a protease domain.In vivoexperiments show that PrgA provides a physical barrier to cellular adhesion, thereby reducing cellular aggregation. This function of PrgA contributes to surface exclusion, reducing the uptake of its cognate plasmid by approximately one order of magnitude. Using variants of PrgA with mutations in the catalytic site we show that the surface exclusion effect is dependent on the activity of the protease domain of PrgA.In silicoanalysis suggest that PrgA can interact with another enterococcal adhesin, PrgB, and that these two proteins have co-evolved. PrgB is a strong virulence factor, and PrgA is involved in post-translational processing of PrgB. Finally, competition mating experiments show that PrgA provides a significant fitness advantage to plasmid-carrying cells.
Anomalous incisor morphology indicates tissue-specific roles forTfap2aandTfap2bin tooth development
Authors: Woodruff Emily D. , Gutierrez Galaxy C. , Van Otterloo Eric , Williams Trevor , Cohn Martin J. 
Published: June 2020

AbstractMice possess two types of teeth that differ in their cusp patterns; incisors have one cusp and molars have multiple cusps. The patterning of these two types of teeth relies on fine-tuning of the reciprocal molecular signaling between dental epithelial and mesenchymal tissues during embryonic development. Here we show that the incisors are populated only at early time points by the neural crest, whereas the molars continue to receive contributions at later stages, revealing a temporal difference that could alter epithelial-mesenchymal signaling dynamics between these two types of teeth. The AP-2 transcription factors, particularlyTfap2aandTfap2b, are essential components of such epithelial-mesenchymal signaling interactions that coordinate craniofacial development in mice and other mammals, but little is known about their roles in the regulation of tooth development and shape. We demonstrate that incisors and molars differ in their temporal and spatial expression ofTfap2aandTfap2b; in particular, at the bud stage,Tfap2ais expressed in both the epithelium and mesenchyme of the incisors and molars but expression ofTfap2bis restricted to the mesenchyme of the molars. Tissue-specific deletions show that loss of the epithelial domain ofTfap2aandTfap2baffects the number and spatial arrangement of the incisors, notably resulting in duplicated lower incisors. In contrast, deletion of these two genes in the mesenchymal domain has little effect on tooth development. Collectively these results implicate epithelial expression ofTfap2aandTfap2bin dorsal-ventral patterning of the incisors and suggest that these genes contribute to morphological differences between anterior (incisor) and posterior (molar) teeth within the mammalian dentition.HighlightsLate-migrating cranial neural crest cells contribute extensively to the developing molar tooth germs but minimally to the incisors.During tooth development, transcription factorsTfap2aandTfap2bare expressed in spatially and temporally dynamic patterns and differ between incisor and molar tooth germs.Epithelial expression ofTfap2aandTfap2bis necessary for incisor development, but mesenchymal expression of these genes is not required.
3D-printed drug testing platform based on a 3D model of aged human skeletal muscle
Authors: Mestre Rafael , García Nerea , Patiño Tania , Guix Maria , Fuentes Judith , Valerio-Santiago Mauricio , Almiñana Núria , Sánchez Samuel 
Published: June 2020

AbstractThree-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessedviaelectrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modelling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline®Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.
Nonlinear ridge regression improves cell-type-specific differential expression analysis
Authors: Takeuchi Fumihiko , Kato Norihiro 
Published: June 2020

AbstractBackgroundEpigenome-wide association studies (EWAS) and differential gene expression analyses are generally performed on tissue samples, which consist of multiple cell types. Cell-type-specific effects of a trait, such as disease, on the omics expression are of interest but difficult or costly to measure experimentally. By measuring omics data for the bulk tissue, cell type composition of a sample can be inferred statistically. Subsequently, cell-type-specific effects are estimated by linear regression that includes terms representing the interaction between the cell type proportions and the trait. This approach involves two issues, scaling and multicollinearity.ResultsFirst, although cell composition is analyzed in linear scale, differential methylation/expression is analyzed suitably in the logit/log scale. To simultaneously analyze two scales, we applied nonlinear regression. Second, we show that the interaction terms are highly collinear, which is obstructive to ordinary regression. To cope with the multicollinearity, we applied ridge regularization. In simulated data, nonlinear ridge regression attained well-balanced sensitivity, specificity and precision. Marginal model attained the lowest precision and highest sensitivity and was the only algorithm to detect weak signal in real data.ConclusionNonlinear ridge regression performed cell-type-specific association test on bulk omics data with well-balanced performance. The omicwas package for R implements nonlinear ridge regression for cell-type-specific EWAS, differential gene expression and QTL analyses. The software is freely available fromhttps://github.com/fumi-github/omicwas
Quantifying risk factors associated with light-induced potato tuber greening in retail stores
Authors: Tanios Sabine , Eyles Alieta , Corkrey Ross , Tegg Robert S. , Thangavel Tamilarasan , Wilson Calum R. 
Published: June 2020

AbstractLight conditions in retail stores may contribute to potato greening. In this study, we aimed to develop a potato tuber greening risk rating model for retail stores based on light quality and intensity parameters. This was achieved by firstly exposing three potato varieties (Nicola, Maranca and Kennebec) to seven specific light wavelengths (370, 420, 450, 530, 630, 660 and 735 nm) to determine the tuber greening propensity. Detailed light quality and intensity measurements from 25 retail stores were then combined with the greening propensity data to develop a tuber greening risk rating model. Our study showed that maximum greening occurred under blue light (450 nm), while 53%, 65% and 75% less occurred under green (530 nm), red (660 nm) and orange (630 nm) light, respectively. Greening risk, which varied between stores, was found to be related to light intensity level, and partially explained potato stock loss in stores. Our results from this study suggested that other in-store management practices, including lighting duration, average potato turnover, and light protection during non-retail periods, likely influence tuber greening risk.
Evaluation validation of a qPCR curve analysis method and conventional approaches
Authors: Zhang Yashu , Li Hongping , Shang Shucheng , Meng Shuoyu , Lin Ting , Zhang Yanhui 
Published: June 2020

AbstractReal-time quantitative polymerase chain reaction (qPCR) is a sensitive and reliable method for mRNA quantification and rapid analysis of gene expression from a large number of starting templates. It is based on the statistical significance of the beginning of exponential phase in real-time PCR kinetics, reflecting quantitative cycle of the initial target quantity and the efficiency of the PCR reaction (the fold increase of product per cycle). We used the large clinical biomaker dataset and 94-replicates-4-dilutions set which was published previously as research tools, then proposed a new qPCR curve analysis method——CqMAN, to determine the position of quantitative cycle as well as the efficiency of the PCR reaction and applied in the calculations. To verify algorithm performance, 20 genes from biomarker and partial data with concentration gradients from 94-replicates-4-dilutions set of MYCN gene were used to compare various publicly available curve analysis methods with our method and established a suitable evaluation index system. The results show that CqMAN method is comparable to other methods and can be a feasible method which applied to our self-developed qPCR data processing and analysis software, providing a simple tool for qPCR analysis.
Neural surprise in somatosensory Bayesian learning
Authors: Gijsen Sam , Grundei Miro , Lange Robert T. , Ostwald Dirk , Blankenburg Felix 
Published: June 2020

AbstractTracking statistical regularities of the environment is important for shaping human behavior and perception. Evidence suggests that the brain learns environmental dependencies using Bayesian principles. However, much remains unknown about the employed algorithms, for somesthesis in particular. Here, we describe the cortical dynamics of the somatosensory learning system to investigate both the form of the generative model as well as its neural surprise signatures. Specifically, we recorded EEG data from 40 participants subjected to a somatosensory roving-stimulus paradigm and performed single-trial modeling across peri-stimulus time in both sensor and source space. Our Bayesian model selection procedure indicates that evoked potentials are best described by a non-hierarchical learning model that tracks transitions between observations using leaky integration. From around 70ms post-stimulus onset, secondary somatosensory cortices are found to represent confidence-corrected surprise as a measure of model inadequacy. Primary somatosensory cortex is found to encode Bayesian surprise, reflecting model updating, from around 140ms. As such, this dissociation indicates that early surprise signals may control subsequent model update rates. In sum, our findings support the hypothesis that early somatosensory processing reflects Bayesian perceptual learning and contribute to an understanding of its precise mechanisms.Author summaryOur environment features statistical regularities, such as a drop of rain predicting imminent rainfall. Despite the importance for behavior and survival, much remains unknown about how these dependencies are learned, particularly for somatosensation. As surprise signalling about novel observations indicates a mismatch between one’s beliefs and the world, it has been hypothesized that surprise computation plays an important role in perceptual learning. By analyzing EEG data from human participants receiving sequences of tactile stimulation, we compare different formulations of surprise and investigate the employed underlying learning model. Our results indicate that the brain estimates transitions between observations. Furthermore, we identified different signatures of surprise computation and thereby provide a dissociation of the neural correlates of belief inadequacy and belief updating. Specifically, early surprise responses from around 70ms were found to signal the need for changes to the model, with encoding of its subsequent updating occurring from around 140ms. These results provide insights into how somatosensory surprise signals may contribute to the learning of environmental statistics.
Transcriptome analyses of β-thalassemia -28 (A>G) mutation using isogenic cell models generated by CRISPR/Cas9 and asymmetric single-stranded oligodeoxynucleotides (assODN)
Authors: Li Jing , Zhou Ziheng , Sun Hai-Xi , Ouyang Wenjie , Dong Guoyi , Liu Tianbin , Ge Lei , Zhang Xiuqing , Liu Chao , Gu Ying 
Published: June 2020

Abstractβ-thalassemia, caused by mutations in the human hemoglobin (HBB) gene, is one of the most common genetic diseases in the world.HBB–28 (A>G) mutation is one of the five most common mutations in China patients with β-thalassemia. However, few studies have been conducted to understand how this mutation affects the expression of pathogenesis related genes including globin genes due to limited homologous clinical materials. Therefore, we first developed an efficient technique using CRISPR/Cas9 combined with asymmetric single-stranded oligodeoxynucleotides (assODN) to generate a K562 cell model ofHBB−28 (A>G) named K562−28 (A>G). Then, we systematically analyzed the differences between K562−28 (A>G)and K562 at the transcriptome level by high-throughput RNA-seq pre- and post-erythrogenic differentiation. We found thatHBB−28 (A>G) mutation not only disturbed the transcription ofHBBbut also decreased the expression ofHBG, which may further aggravate the thalassemia phenotype and partially explain the severer clinical outcome of β-thalassemia patients withHBB−28 (A>G) mutation. Moreover, we found K562−28 (A>G)cell line is more sensitive to hypoxia and showed a defective erythrogenic program compared with K562 before differentiation. In agreement, p38MAPK and ERK pathway are hyperactivated in K562−28 (A>G)after differentiation. Importantly, all above mentioned abnormalities in K562−28 (A>G)were reversed after correction of this mutation with CRISPR/Cas and assODN, confirming the specificity of these phenotypes. Overall, this is the first time to analyze the effects of theHBB- 28 (A>G) mutation at whole-transcriptome level based on isogenic cell lines, providing a landscape for further investigation of the mechanism of β-thalassemia withHBB−28 (A>G) mutation.
Dose-response modelling of total haemoglobin mass to hypoxic dose in elite speed skaters
Authors: Vinogradov Mikhail , Zelenkova Irina 
Published: June 2020

AbstractThe aim of the present study is the modelling of the total haemoglobin mass responses in altitude environment with the dose-response model in elite endurance athletes and comparison different existing approaches in the quantification of hypoxic dose.Data from seven healthy elite endurance athletes specialised in middle distance speed skating participated in the study: six males (24±1.8 years, 182 ±0.3 cm, 84 ±1.5 kg, BMI 23.2±0.6 kg/m2, 59.3±1.5 ml/kg/min) and one female (21 years, 164 cm, 56 kg, BMI 17.1 kg/m2, 59.9 ml/kg/min). Data were collected during a 3-month training period which included two training camps (14 +14 days) at sea level and two training camps (21+21 days) at altitude of 1224 m and 1850 m above sea level. Total haemoglobin mass (tHb-mass) were measured before the start of the season (baseline) and before and after each training camp (seven measurements) using an optimized CO-rebreathing method, training loads and oxygen saturation at altitude were measured and hypoxic dose were calculated.Mean total haemoglobin mass for the male group at the base line were 1067±83 g, before the training camp 1 were 1095±82 g, after TC1 1113±105 g, before the training camp 2 (TC2) 1107±88 g, after TC2 1138±104 g. For the female athlete at the base line were 570 g, after TC1 564 g, after TC2 582 g.The increase of tHb-mass after TC2 were 3,25% and were significant (p<0,005). Mean hypoxic dose for the male group TC1 were %·h (98%) 1078±157, %·h (95%) 79±57, and km.h 473±1 and at TC2 were %·h(98%) 1586±585, %·h (95%) 422±182, and km.h 893±18 and were different from TC1 (p<0,05) for %·h (95%) and km.h methods. For the female athlete hypoxic dose at TC1 were %·h (98%) 970, %·h (95%) 32, and km.h 470 and at TC2 were %·h(98%) 1587, %·h (95%) 289, and km.h 900.The relationship between hypoxic dose and haematological response was analysed with a non-linear model. The magnitude of the increase of the total haemoglobin mass were investigated using simulation procedures based upon individual responses to the hypoxic dose. We introduced a measurement error to the list square method as a way of avoiding overfitting problem. Dose-response mathematical model between hypoxic dose and total haemoglobin mass was developed. Modelled total haemoglobin mass was within measurement error range. This model is suitable for the computer simulations. The individual response to hypoxic dose due to model data was different. Maximal values in total haemoglobin mass that can be achieved by male athletes according to the model was 1321.9 ± 32 g. The model predicted that (τ) erythrocyte life span is 73.8 ± 9.0 days. Moreover, highest value of individual tHb-mass increase after returning to the sea level according to the model was16.3 ±0.7 days.The model developed in the current study describes the time course of total haemoglobin mass during altitude exposure and post-altitude decline in elite speed skaters.