bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calreticulin del52 and ins5 knock-in mice recapitulate different myeloproliferative phenotypes observed in patients with MPN
Authors: Benlabiod Camélia , Cacemiro Maira da Costa , Nédélec Audrey , Edmond Valérie , Muller Delphine , Rameau Philippe , Touchard Laure , Gonin Patrick , Constantinescu Stefan N. , Raslova Hana , Villeval Jean-Luc , Vainchenker William , Plo Isabelle , Marty Caroline 
Published: September 2020

AbstractSomatic mutations in the calreticulin (CALR) gene are associated with approximately 30% of essential thrombocythemia (ET) and primary myelofibrosis (PMF). CALR mutations, including the two most frequent 52 bp deletion (del52) and 5 bp insertion (ins5), induce a frameshift to the same alternative reading frame generating new C-terminal tails. In patients, del52 and ins5 induce two phenotypically distinct myeloproliferative neoplasms (MPNs). They are equally found in ET, but del52 is more frequent in PMF. We generated heterozygous and homozygous conditional inducible knock-in (KI) mice expressing a chimeric murine CALR del52 or ins5 with the human mutated C-terminal tail to investigate their pathogenic effects on hematopoiesis. Del52 induces greater phenotypic changes than ins5 including thrombocytosis, leukocytosis, splenomegaly, bone marrow hypocellularity, megakaryocytic lineage amplification, expansion and competitive advantage of the hematopoietic stem cell compartment. Homozygosity amplifies these features, suggesting a distinct contribution of homozygous clones to human MPNs. Moreover, homozygous del52 KI mice display features of a penetrant myelofibrosis-like disorder with extramedullary hematopoiesis linked to splenomegaly, megakaryocyte hyperplasia and the presence of reticulin fibers. Overall, modeling del52 and ins5 mutations in mice successfully recapitulates the differences in phenotypes observed in patients.
Interleukin-8 as a candidate for thymoma identification and recurrence surveillance
Authors: Gao Shilin , Jiang Jiahao , Jin Chun , Gao Jian , Xiong Dian , Yang Pengjie , Cui Shuzhong , Yang Wenhao , Leng Qibin , Dong Jihong , Chen Gang , Liu Junzhen , Wang Li , Ke Aiwu , Wang Haikun , Ding Jianyong 
Published: September 2020

AbstractThymoma is the most common tumor of the anterior mediastinum. Routine imaging methods such as computed tomography or magnetic resonance imaging often lead to misdiagnosis between thymoma and other thymic abnormalities. Therefore, urgently needed is to develop a new diagnostic strategy. Here we identify interleukin-8 (IL-8) as a biomarker for auxiliary diagnosis of thymoma. We find that IL-8 levels in naïve T cells are markedly elevated in patients with thymoma compared to those with other thymic tumors. IL-8 levels in naive T cells are significantly decreased after surgical resection in thymoma patients, and rise again when thymoma recurs. A receiver operating characteristic curve analysis shows that IL-8 evaluation performs well in thymoma identification, with high specificities and sensitivities. We also observe significant clinical relevance between IL-8 levels in naïve T cells and clinicopathological features. In conclusion, our study suggests that IL-8 is a biomarker for thymoma identification and recurrence surveillance.
Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma
Authors: Yang Zhenlin , Xu Jiachen , Li Lin , Li Renda , Wang Yalong , Tian Yanhua , Guo Wei , Wang Zhijie , Tan Fengwei , Ying Jianming , Jiao Yuchen , Gao Shugeng , Wang Jie , Gao Yibo , He Jie 
Published: September 2020

AbstractPulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.
SV-HotSpot: detection and visualization of hotspots targeted by structural variants associated with gene expression
Authors: Eteleeb Abdallah M. , Quigley David A. , Zhao Shuang G. , Pham Duy , Yang Rendong , Dehm Scott M. , Luo Jingqin , Feng Felix Y. , Dang Ha X. , Maher Christopher A. 
Published: September 2020

AbstractWhole genome sequencing (WGS) has enabled the discovery of genomic structural variants (SVs), including those targeting intergenic and intronic non-coding regions that eluded previous exome focused strategies. However, the field currently lacks an automated tool that analyzes SV candidates to identify recurrent SVs and their targeted sites (hotspot regions), visualizes these genomic events within the context of various functional elements, and evaluates their potential effect on gene expression. To address this, we developed SV-HotSpot, an automated tool that integrates SV candidates, copy number alterations, gene expression, and genome annotations (e.g. gene and regulatory elements) to discover, annotate, and visualize recurrent SVs and their targeted hotspot regions that may affect gene expression. We applied SV-HotSpot to WGS and matched transcriptome data from metastatic castration resistant prostate cancer patients and rediscovered recurrent SVs targeting coding and non-coding functional elements known to promote prostate cancer progression and metastasis. SV-HotSpot provides a valuable resource to integrate SVs, gene expression, and genome annotations for discovering biologically relevant SVs altering coding and non-coding genome. SV-HotSpot is available athttps://github.com/ChrisMaherLab/SV-HotSpot.
Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection
Authors: Connell Bridgette J. , Hermans Lucas E. , Wensing Annemarie M. J. , Schellens Ingrid , Schipper Pauline J. , van Ham Petra M. , de Jong Dorien T. C. M. , Otto Sigrid , Mathe Tholakele , Moraba Robert , Borghans José A. M. , Papathanasopoulos Maria A. , Kruize Zita , Venter Francois W. D. , Kootstra Neeltje A. , Tempelman Hugo , Tesselaar Kiki , Nijhuis Monique 
Published: September 2020

AbstractHIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003–1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065–1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies.
FADS genetic and metabolomic analyses identify the ∆5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids
Authors: Reynolds Lindsay M. , Dutta Rahul , Seeds Michael C. , Lake Kirsten N. , Hallmark Brian , Mathias Rasika A. , Howard Timothy D. , Chilton Floyd H. 
Published: September 2020

AbstractHumans have undergone intense evolutionary selection to optimize their capacity to generate necessary quantities of long chain (LC-) polyunsaturated fatty acid (PUFA)-containing lipids. To better understand the impact of genetic variation within a locus of three FADS genes (FADS1, FADS2, and FADS3) on a diverse family of lipids, we examined the associations of 247 lipid metabolites (including four major classes of LC-PUFA-containing molecules and signaling molecules) with common and low-frequency genetic variants located within the FADS locus. Genetic variation in the FADS locus was strongly associated (p < 1.2 × 10–8) with 52 LC-PUFA-containing lipids and signaling molecules, including free fatty acids, phospholipids, lyso-phospholipids, and an endocannabinoid. Notably, the majority (80%) of FADS-associated lipids were not significantly associated with genetic variants outside of this FADS locus. These findings highlight the central role genetic variation at the FADS locus plays in regulating levels of physiologically critical LC-PUFA-containing lipids that participate in innate immunity, energy homeostasis, and brain development/function.
Interplay of social distancing and border restrictions for pandemics via the epidemic renormalisation group framework
Authors: Cacciapaglia Giacomo , Sannino Francesco 
Published: September 2020

AbstractOne of the biggest threats to humanity are pandemics. In our global society they can rage around the world with an immense toll in terms of human, economic and social impact. Forecasting the spreading of a pandemic is, therefore, paramount in helping governments to enforce a number of social and economic measures, apt at curbing the pandemic and dealing with its aftermath. We demonstrate that the epidemic renormalisation group approach to pandemics provides an effective and simple way to investigate the dynamics of disease transmission and spreading across different regions of the world. The framework also allows for reliable projections on the impact of travel limitations and social distancing measures on global epidemic spread. We test and calibrate it on reported COVID-19 cases while unveiling the mechanism that governs the delay in the relative peaks of newly infected cases among different regions of the globe. We discover that social distancing measures are more effective than travel limitations across borders in delaying the epidemic peak. We further provide the link to compartmental models such as the time-honoured SIR-like models. We also show how to generalise the framework to account for the interactions across several regions of the world, replacing or complementing large scale simulations.
Two coupled chains are simpler than one: field-induced chirality in a frustrated spin ladder
Authors: Pikulski Marek , Shiroka Toni , Casola Francesco , Reyes Arneil P. , Kuhns Philip L. , Wang Shuang , Ott Hans-Rudolf , Mesot Joël 
Published: September 2020

AbstractAlthough the frustrated (zigzag) spin chain is the Drosophila of frustrated magnetism, our understanding of a pair of coupled zigzag chains (frustrated spin ladder) in a magnetic field is still lacking. We address this problem through nuclear magnetic resonance (NMR) experiments on BiCu$$_2$$

2

PO$$_6$$

6

in magnetic fields up to 45 T, revealing a field-induced spiral magnetic structure. Conjointly, we present advanced numerical calculations showing that even a moderate rung coupling dramatically simplifies the phase diagram below half-saturation magnetization by stabilizing a field-induced chiral phase. Surprisingly for a one-dimensional model, this phase and its response to Dzyaloshinskii-Moriya (DM) interactions adhere to classical expectations. While explaining the behavior at the highest accessible magnetic fields, our results imply a different origin for the solitonic phases occurring at lower fields in BiCu$$_2$$

2

PO$$_6$$

6

. An exciting possibility is that the known, DM-mediated coupling between chirality and crystal lattice may give rise to a new kind of spin-Peierls instability.
Revealing soil legacy phosphorus to promote sustainable agriculture in Brazil
Authors: Pavinato Paulo S. , Cherubin Maurício R. , Soltangheisi Amin , Rocha Gustavo C. , Chadwick Dave R. , Jones Davey L. 
Published: September 2020

AbstractExploiting native soil phosphorus (P) and the large reservoirs of residual P accumulated over decades of cultivation, namely “legacy P”, has great potential to overcome the high demand of P fertilisers in Brazilian cropping systems. Long-term field experiments have shown that a large proportion (> 70%) of the surplus P added via fertilisers remains in the soil, mainly in forms not readily available to crops. An important issue is if the amount of legacy P mobilized from soil is sufficient for the crop nutritional demand and over how long this stored soil P can be effectively ‘mined’ by crops in a profitable way. Here we mapped the spatial–temporal distribution of legacy P over the past 50 years, and discussed possible agricultural practices that could increase soil legacy P usage by plants in Brazil. Mineral fertiliser and manure applications have resulted in ~ 33.4 Tg of legacy P accumulated in the agricultural soils from 1967 to 2016, with a current annual surplus rate of 1.6 Tg. Following this same rate, soil legacy P may reach up to 106.5 Tg by 2050. Agricultural management practices to enhance soil legacy P usage by crops includes increasing soil pH by liming, crop rotation, double-cropping, inter-season cover crops, no-tillage system and use of modern fertilisers, in addition to more efficient crop varieties and inoculation with P solubilising microorganisms. The adoption of these practices could increase the use efficiency of P, substantially reducing the new input of fertilisers and thus save up to 31.8 Tg of P fertiliser use (US$ 20.8 billion) in the coming decades. Therefore, exploring soil legacy P is imperative to reduce the demand for mineral fertilisers while promoting long-term P sustainability in Brazil.
Distinct chemotactic behavior in the original Escherichia coli K-12 depending on forward-and-backward swimming, not on run-tumble movements
Authors: Kinosita Yoshiaki , Ishida Tsubasa , Yoshida Myu , Ito Rie , Morimoto Yusuke V. , Goto Kazuki , Berry Richard M. , Nishizaka Takayuki , Sowa Yoshiyuki 
Published: September 2020

AbstractMost motile bacteria are propelled by rigid, helical, flagellar filaments and display distinct swimming patterns to explore their favorable environments. Escherichia coli cells have a reversible rotary motor at the base of each filament. They exhibit a run-tumble swimming pattern, driven by switching of the rotational direction, which causes polymorphic flagellar transformation. Here we report a novel swimming mode in E. coli ATCC10798, which is one of the original K-12 clones. High-speed tracking of single ATCC10798 cells showed forward and backward swimming with an average turning angle of 150°. The flagellar helicity remained right-handed with a 1.3 μm pitch and 0.14 μm helix radius, which is consistent with the feature of a curly type, regardless of motor switching; the flagella of ATCC10798 did not show polymorphic transformation. The torque and rotational switching of the motor was almost identical to the E. coli W3110 strain, which is a derivative of K-12 and a wild-type for chemotaxis. The single point mutation of N87K in FliC, one of the filament subunits, is critical to the change in flagellar morphology and swimming pattern, and lack of flagellar polymorphism. E. coli cells expressing FliC(N87K) sensed ascending a chemotactic gradient in liquid but did not spread on a semi-solid surface. Based on these results, we concluded that a flagellar polymorphism is essential for spreading in structured environments.
Identifying volatile organic compounds used for olfactory navigation by homing pigeons
Authors: Zannoni Nora , Wikelski Martin , Gagliardo Anna , Raza Atif , Kramer Stefan , Seghetti Chiara , Wang Nijing , Edtbauer Achim , Williams Jonathan 
Published: September 2020

AbstractMany bird species have the ability to navigate home after being brought to a remote, even unfamiliar location. Environmental odours have been demonstrated to be critical to homeward navigation in over 40 years of experiments, yet the chemical identity of the odours has remained unknown. In this study, we investigate potential chemical navigational cues by measuring volatile organic compounds (VOCs): at the birds’ home-loft; in selected regional forest environments; and from an aircraft at 180 m. The measurements showed clear regional, horizontal and vertical spatial gradients that can form the basis of an olfactory map for marine emissions (dimethyl sulphide, DMS), biogenic compounds (terpenoids) and anthropogenic mixed air (aromatic compounds), and temporal changes consistent with a sea-breeze system. Air masses trajectories are used to examine GPS tracks from released birds, suggesting that local DMS concentrations alter their flight directions in predictable ways. This dataset reveals multiple regional-scale real-world chemical gradients that can form the basis of an olfactory map suitable for homing pigeons.
Structural and functional modelling of SARS-CoV-2 entry in animal models
Authors: Brooke Greg N. , Prischi Filippo 
Published: September 2020

AbstractSARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
NMR resonance assignment and dynamics of profilin from Heimdallarchaeota
Authors: Haq Syed Razaul , Survery Sabeen , Hurtig Fredrik , Lindås Ann-Christin , Chi Celestine N. 
Published: September 2020

AbstractThe origin of the eukaryotic cell is an unsettled scientific question. The Asgard superphylum has emerged as a compelling target for studying eukaryogenesis due to the previously unseen diversity of eukaryotic signature proteins. However, our knowledge about these proteins is still relegated to metagenomic data and very little is known about their structural properties. Additionally, it is still unclear if these proteins are functionally homologous to their eukaryotic counterparts. Here, we expressed, purified and structurally characterized profilin from Heimdallarchaeota in the Asgard superphylum. The structural analysis shows that while this profilin possesses similar secondary structural elements as eukaryotic profilin, it contains additional secondary structural elements that could be critical for its function and an indication of divergent evolution.
Modeling root system growth around obstacles
Authors: Jin Wencheng , Aufrecht Jayde , Patino-Ramirez Fernando , Cabral Heidy , Arson Chloé , Retterer Scott T. 
Published: September 2020

AbstractState-of-the-Art models of Root System Architecture (RSA) do not allow simulating root growth around rigid obstacles. Yet, the presence of obstacles can be highly disruptive to the root system. We grew wheat seedlings in sealed petri dishes without obstacle and in custom 3D-printed rhizoboxes containing obstacles. Time-lapse photography was used to reconstruct the wheat root morphology network. We used the reconstructed wheat root network without obstacle to calibrate an RSA model implemented in the R-SWMS software. The root network with obstacles allowed calibrating the parameters of a new function that models the influence of rigid obstacles on wheat root growth. Experimental results show that the presence of a rigid obstacle does not affect the growth rate of the wheat root axes, but that it does influence the root trajectory after the main axis has passed the obstacle. The growth recovery time, i.e. the time for the main root axis to recover its geotropism-driven growth, is proportional to the time during which the main axis grows along the obstacle. Qualitative and quantitative comparisons between experimental and numerical results show that the proposed model successfully simulates wheat RSA growth around obstacles. Our results suggest that wheat roots follow patterns that could inspire the design of adaptive engineering flow networks.
Functional validation of DvABCB1 as a receptor of Cry3 toxins in western corn rootworm, Diabrotica virgifera virgifera
Authors: Niu Xiping , Kassa Adane , Hasler James , Griffin Samantha , Perez-Ortega Claudia , Procyk Lisa , Zhang Jun , Kapka-Kitzman Deirdre M. , Nelson Mark E. , Lu Albert 
Published: September 2020

AbstractWestern corn rootworm (WCR), Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is a serious insect pest in the major corn growing areas of North America and in parts of Europe. WCR populations with resistance to Bacillus thuringiensis (Bt) toxins utilized in commercial transgenic traits have been reported, raising concerns over their continued efficacy in WCR management. Understanding the modes of action of Bt toxins is important for WCR control and resistance management. Although different classes of proteins have been identified as Bt receptors for lepidopteran insects, identification of receptors in WCR has been limited with no reports of functional validation. Our results demonstrate that heterologous expression of DvABCB1 in Sf9 and HEK293 cells conferred sensitivity to the cytotoxic effects of Cry3A toxins. The result was further validated using knockdown of DvABCB1 by RNAi which rendered WCR larvae insensitive to a Cry3A toxin. However, silencing of DvABCB2 which is highly homologous to DvABCB1 at the amino acid level, did not reduce the sensitivity of WCR larvae to a Cry3A toxin. Furthermore, our functional studies corroborate different mode-of-actions for other insecticidal proteins including Cry34Ab1/35Ab1, Cry6Aa1, and IPD072Aa against WCR. Finally, reduced expression and alternatively spliced transcripts of DvABCB1 were identified in a mCry3A-resistant strain of WCR. Our results provide the first clear demonstration of a functional receptor in the molecular mechanism of Cry3A toxicity in WCR and confirmed its role in the mechanism of resistance in a mCry3A resistant strain of WCR.