bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt tolerance-based niche differentiation of soil ammonia oxidizers
Authors: Sun Xiangxin , Zhao Jun , Zhou Xue , Bei Qicheng , Xia Weiwei , Zhao Bingzi , Zhang Jiabao , Jia Zhongjun 
Published: August 2021

Abstract
Ammonia oxidizers are key players in the global nitrogen cycle, yet little is known about their ecological performances and adaptation strategies for growth in saline terrestrial ecosystems. This study combined 13C-DNA stable-isotope probing (SIP) microcosms with amplicon and shotgun sequencing to reveal the composition and genomic adaptations of active ammonia oxidizers in a saline-sodic (solonetz) soil with high salinity and pH (20.9 cmolc exchangeable Na+ kg−1 soil and pH 9.64). Both ammonia-oxidizing archaea (AOA) and bacteria (AOB) exhibited strong nitrification activities, although AOB performed most of the ammonia oxidation observed in the solonetz soil and in the farmland soil converted from solonetz soil. Members of the Nitrosococcus, which are more often associated with aquatic habitats, were identified as the dominant ammonia oxidizers in the solonetz soil with the first direct labeling evidence, while members of the Nitrosospira were the dominant ammonia oxidizers in the farmland soil, which had much lower salinity and pH. Metagenomic analysis of “Candidatus Nitrosococcus sp. Sol14”, a new species within the Nitrosococcus lineage, revealed multiple genomic adaptations predicted to facilitate osmotic and pH homeostasis in this extreme habitat, including direct Na+ extrusion/H+ import and the ability to increase intracellular osmotic pressure by accumulating compatible solutes. Comparative genomic analysis revealed that variation in salt-tolerance mechanisms was the primary driver for the niche differentiation of ammonia oxidizers in saline-sodic soils. These results demonstrate how ammonia oxidizers can adapt to saline-sodic soil with excessive Na+ content and provide new insights on the nitrogen cycle in extreme terrestrial ecosystems.
Analysis of genetic differences between psychiatric disorders: exploring pathways and cell types/tissues involved and ability to differentiate the disorders by polygenic scores
Authors: Rao Shitao , Yin Liangying , Xiang Yong , So Hon-Cheong 
Published: August 2021

AbstractAlthough displaying genetic correlations, psychiatric disorders are clinically defined as categorical entities as they each have distinguishing clinical features and may involve different treatments. Identifying differential genetic variations between these disorders may reveal how the disorders differ biologically and help to guide more personalized treatment. Here we presented a statistical framework and comprehensive analysis to identify genetic markers differentially associated with various psychiatric disorders/traits based on GWAS summary statistics, covering 18 psychiatric traits/disorders and 26 comparisons. We also conducted comprehensive analysis to unravel the genes, pathways and SNP functional categories involved, and the cell types and tissues implicated. We also assessed how well one could distinguish between psychiatric disorders by polygenic risk scores (PRS). SNP-based heritabilities (h2snp) were significantly larger than zero for most comparisons. Based on current GWAS data, PRS have mostly modest power to distinguish between psychiatric disorders. For example, we estimated that AUC for distinguishing schizophrenia from major depressive disorder (MDD), bipolar disorder (BPD) from MDD and schizophrenia from BPD were 0.694, 0.602 and 0.618, respectively, while the maximum AUC (based on h2snp) were 0.763, 0.749 and 0.726, respectively. We also uncovered differences in each pair of studied traits in terms of their differences in genetic correlation with comorbid traits. For example, clinically defined MDD appeared to more strongly genetically correlated with other psychiatric disorders and heart disease, when compared to non-clinically defined depression in UK Biobank. Our findings highlight genetic differences between psychiatric disorders and the mechanisms involved. PRS may help differential diagnosis of selected psychiatric disorders in the future with larger GWAS samples.
Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England
Authors: Smith Matthew J. , Fernandez Miguel Angel Luque , Belot Aurélien , Quartagno Matteo , Bonaventure Audrey , Majano Sara Benitez , Rachet Bernard , Njagi Edmund Njeru 
Published: August 2021

AbstractIntroductionDiagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005–2013.MethodsMultivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables.ResultsWe included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40–1.73; FL: odds ratio 1.80, CI 1.45–2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities.ConclusionsUnderlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.
Monolithic polymeric porous superhydrophobic material with pneumatic plastron stabilization for functionally durable drag reduction in blood-contacting biomedical applications
Authors: Marlena Jennifer , Tan Justin Kok Soon , Lin Zenggan , Li David Xinzheyang , Zhao Boxin , Leo Hwa Liang , Kim Sangho , Yap Choon Hwai 
Published: August 2021

AbstractSuperhydrophobic (SHP) surfaces can provide substantial reductions in flow drag forces and reduce blood damage in cardiovascular medical devices. However, strategies for functional durability are necessary, as many SHP surfaces have low durability under abrasion or strong fluid jetting or eventually lose their air plastron and slip-flow capabilities due to plastron gas dissolution, high fluid pressure, or fouling. Here, we present a functional material that extends the functional durability of superhydrophobic slip flow. Facile modification of a porous superhydrophobic polytetrafluoroethylene (PTFE, Teflon) foam produced suitable surface structures to enable fluid slip flow and resist protein fouling. Its monolithic nature offered abrasion durability, while its porosity allowed pressurized air to be supplied to resist fluid impalement and to replenish the air plastron lost to the fluid through dissolution. Active pore pressure control could resist high fluid pressures and turbulent flow conditions across a wide range of applied pressures. The pneumatically stabilized material yielded large drag reductions (up to 50%) even with protein fouling, as demonstrated from high-speed water jetting and closed loop pressure drop tests. Coupled with its high hemocompatibility and impaired protein adsorption, this easily fabricated material can be viable for incorporation into blood-contacting medical devices.
Structures of tmRNA and SmpB as they transit through the ribosome
Authors: Guyomar Charlotte , D’Urso Gaetano , Chat Sophie , Giudice Emmanuel , Gillet Reynald 
Published: August 2021

AbstractIn bacteria, trans-translation is the main rescue system, freeing ribosomes stalled on defective messenger RNAs. This mechanism is driven by small protein B (SmpB) and transfer-messenger RNA (tmRNA), a hybrid RNA known to have both a tRNA-like and an mRNA-like domain. Here we present four cryo-EM structures of the ribosome during trans-translation at resolutions from 3.0 to 3.4 Å. These include the high-resolution structure of the whole pre-accommodated state, as well as structures of the accommodated state, the translocated state, and a translocation intermediate. Together, they shed light on the movements of the tmRNA-SmpB complex in the ribosome, from its delivery by the elongation factor EF-Tu to its passage through the ribosomal A and P sites after the opening of the B1 bridges. Additionally, we describe the interactions between the tmRNA-SmpB complex and the ribosome. These explain why the process does not interfere with canonical translation.
A direct interareal feedback-to-feedforward circuit in primate visual cortex
Authors: Siu Caitlin , Balsor Justin , Merlin Sam , Federer Frederick , Angelucci Alessandra 
Published: August 2021

AbstractThe mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area-specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.
Nuclear export and translation of circular repeat-containing intronic RNA in C9ORF72-ALS/FTD
Authors: Wang Shaopeng , Latallo Malgorzata J. , Zhang Zhe , Huang Bo , Bobrovnikov Dmitriy G. , Dong Daoyuan , Livingston Nathan M. , Tjoeng Wilson , Hayes Lindsey R. , Rothstein Jeffrey D. , Ostrow Lyle W. , Wu Bin , Sun Shuying 
Published: August 2021

AbstractC9ORF72 hexanucleotide GGGGCC repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat-containing RNA mediates toxicity through nuclear granules and dipeptide repeat (DPR) proteins produced by repeat-associated non-AUG translation. However, it remains unclear how the intron-localized repeats are exported and translated in the cytoplasm. We use single molecule imaging approach to examine the molecular identity and spatiotemporal dynamics of the repeat RNA. We demonstrate that the spliced intron with G-rich repeats is stabilized in a circular form due to defective lariat debranching. The spliced circular intron, instead of pre-mRNA, serves as the translation template. The NXF1-NXT1 pathway plays an important role in the nuclear export of the circular intron and modulates toxic DPR production. This study reveals an uncharacterized disease-causing RNA species mediated by repeat expansion and demonstrates the importance of RNA spatial localization to understand disease etiology.
Wide range continuously tunable and fast thermal switching based on compressible graphene composite foams
Authors: Du Tingting , Xiong Zixin , Delgado Luis , Liao Weizhi , Peoples Joseph , Kantharaj Rajath , Chowdhury Prabudhya Roy , Marconnet Amy , Ruan Xiulin 
Published: August 2021

AbstractThermal switches have gained intense interest recently for enabling dynamic thermal management of electronic devices and batteries that need to function at dramatically varied ambient or operating conditions. However, current approaches have limitations such as the lack of continuous tunability, low switching ratio, low speed, and not being scalable. Here, a continuously tunable, wide-range, and fast thermal switching approach is proposed and demonstrated using compressible graphene composite foams. Large (~8x) continuous tuning of the thermal resistance is achieved from the uncompressed to the fully compressed state. Environmental chamber experiments show that our variable thermal resistor can precisely stabilize the operating temperature of a heat generating device while the ambient temperature varies continuously by ~10 °C or the heat generation rate varies by a factor of 2.7. This thermal device is promising for dynamic control of operating temperatures in battery thermal management, space conditioning, vehicle thermal comfort, and thermal energy storage.
Retention and deformation of the blue phases in liquid crystalline elastomers
Authors: Schlafmann Kyle R. , White Timothy J. 
Published: August 2021

AbstractThe blue phases are observed in highly chiral liquid crystalline compositions that nascently organize into a three-dimensional, crystalline nanostructure. The periodicity of the unit cell lattice spacing is on the order of the wavelength of visible light and accordingly, the blue phases exhibit a selective reflection as a photonic crystal. Here, we detail the synthesis of liquid crystalline elastomers that retain blue phase I, blue phase II, and blue phase III. The mechanical properties and optical reconfiguration via deformation of retained blue phases are contrasted to the cholesteric phase in fully solid elastomers with glass transition temperatures below room temperature. Mechanical deformation and chemical swelling of the lightly crosslinked polymer networks induces lattice asymmetry in the blue phase evident in the tuning of the selective reflection. The lattice periodicity of the blue phase elastomer is minimally affected by temperature. The oblique lattice planes of the blue phase tilt and red-shift in response to mechanical deformation. The retention of the blue phases in fully solid, elastomeric films could enable functional implementations in photonics, sensing, and energy applications.
RSPO3 is important for trabecular bone and fracture risk in mice and humans
Authors: Nilsson Karin H. , Henning Petra , El Shahawy Maha , Nethander Maria , Andersen Thomas Levin , Ejersted Charlotte , Wu Jianyao , Gustafsson Karin L. , Koskela Antti , Tuukkanen Juha , Souza Pedro P. C. , Tuckermann Jan , Lorentzon Mattias , Ruud Linda Engström , Lehtimäki Terho , Tobias Jon H. , Zhou Sirui , Lerner Ulf H. , Richards J. Brent , Movérare-Skrtic Sofia , Ohlsson Claes 
Published: August 2021

AbstractWith increasing age of the population, countries across the globe are facing a substantial increase in osteoporotic fractures. Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here we show that the fracture reducing allele at the RSPO3 locus associate with increased RSPO3 expression both at the mRNA and protein levels, increased trabecular bone mineral density and reduced risk mainly of distal forearm fractures in humans. We also demonstrate that RSPO3 is expressed in osteoprogenitor cells and osteoblasts and that osteoblast-derived RSPO3 is the principal source of RSPO3 in bone and an important regulator of vertebral trabecular bone mass and bone strength in adult mice. Mechanistic studies revealed that RSPO3 in a cell-autonomous manner increases osteoblast proliferation and differentiation. In conclusion, RSPO3 regulates vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.
Frustrated self-assembly of non-Euclidean crystals of nanoparticles
Authors: Serafin Francesco , Lu Jun , Kotov Nicholas , Sun Kai , Mao Xiaoming 
Published: August 2021

AbstractSelf-organized complex structures in nature, e.g., viral capsids, hierarchical biopolymers, and bacterial flagella, offer efficiency, adaptability, robustness, and multi-functionality. Can we program the self-assembly of three-dimensional (3D) complex structures using simple building blocks, and reach similar or higher level of sophistication in engineered materials? Here we present an analytic theory for the self-assembly of polyhedral nanoparticles (NPs) based on their crystal structures in non-Euclidean space. We show that the unavoidable geometrical frustration of these particle shapes, combined with competing attractive and repulsive interparticle interactions, lead to controllable self-assembly of structures of complex order. Applying this theory to tetrahedral NPs, we find high-yield and enantiopure self-assembly of helicoidal ribbons, exhibiting qualitative agreement with experimental observations. We expect that this theory will offer a general framework for the self-assembly of simple polyhedral building blocks into rich complex morphologies with new material capabilities such as tunable optical activity, essential for multiple emerging technologies.
The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis
Authors: Yuan Ting , Annamalai Karthika , Naik Shruti , Lupse Blaz , Geravandi Shirin , Pal Anasua , Dobrowolski Aleksandra , Ghawali Jaee , Ruhlandt Marina , Gorrepati Kanaka Durga Devi , Azizi Zahra , Lim Dae-Sik , Maedler Kathrin , Ardestani Amin 
Published: August 2021

AbstractDiabetes results from a decline in functional pancreatic β-cells, but the molecular mechanisms underlying the pathological β-cell failure are poorly understood. Here we report that large-tumor suppressor 2 (LATS2), a core component of the Hippo signaling pathway, is activated under diabetic conditions and induces β-cell apoptosis and impaired function. LATS2 deficiency in β-cells and primary isolated human islets as well as β-cell specific LATS2 ablation in mice improves β-cell viability, insulin secretion and β-cell mass and ameliorates diabetes development. LATS2 activates mechanistic target of rapamycin complex 1 (mTORC1), a physiological suppressor of autophagy, in β-cells and genetic and pharmacological inhibition of mTORC1 counteracts the pro-apoptotic action of activated LATS2. We further show a direct interplay between Hippo and autophagy, in which LATS2 is an autophagy substrate. On the other hand, LATS2 regulates β-cell apoptosis triggered by impaired autophagy suggesting an existence of a stress-sensitive multicomponent cellular loop coordinating β-cell compensation and survival. Our data reveal an important role for LATS2 in pancreatic β-cell turnover and suggest LATS2 as a potential therapeutic target to improve pancreatic β-cell survival and function in diabetes.
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Authors: Skead Kimberly , Ang Houle Armande , Abelson Sagi , Agbessi Mawusse , Bruat Vanessa , Lin Boxi , Soave David , Shlush Liran , Wright Stephen , Dick John , Morris Quaid , Awadalla Philip 
Published: August 2021

AbstractAge-related clonal hematopoiesis (ARCH) is characterized by age-associated accumulation of somatic mutations in hematopoietic stem cells (HSCs) or their pluripotent descendants. HSCs harboring driver mutations will be positively selected and cells carrying these mutations will rise in frequency. While ARCH is a known risk factor for blood malignancies, such as Acute Myeloid Leukemia (AML), why some people who harbor ARCH driver mutations do not progress to AML remains unclear. Here, we model the interaction of positive and negative selection in deeply sequenced blood samples from individuals who subsequently progressed to AML, compared to healthy controls, using deep learning and population genetics. Our modeling allows us to discriminate amongst evolutionary classes with high accuracy and captures signatures of purifying selection in most individuals. Purifying selection, acting on benign or mildly damaging passenger mutations, appears to play a critical role in preventing disease-predisposing clones from rising to dominance and is associated with longer disease-free survival. Through exploring a range of evolutionary models, we show how different classes of selection shape clonal dynamics and health outcomes thus enabling us to better identify individuals at a high risk of malignancy.
The pathogenesis of mesothelioma is driven by a dysregulated translatome
Authors: Grosso Stefano , Marini Alberto , Gyuraszova Katarina , Voorde Johan Vande , Sfakianos Aristeidis , Garland Gavin D. , Tenor Angela Rubio , Mordue Ryan , Chernova Tanya , Morone Nobu , Sereno Marco , Smith Claire P. , Officer Leah , Farahmand Pooyeh , Rooney Claire , Sumpton David , Das Madhumita , Teodósio Ana , Ficken Catherine , Martin Maria Guerra , Spriggs Ruth V. , Sun Xiao-Ming , Bushell Martin , Sansom Owen J. , Murphy Daniel , MacFarlane Marion , Le Quesne John P. C. , Willis Anne E. 
Published: August 2021

AbstractMalignant mesothelioma (MpM) is an aggressive, invariably fatal tumour that is causally linked with asbestos exposure. The disease primarily results from loss of tumour suppressor gene function and there are no ‘druggable’ driver oncogenes associated with MpM. To identify opportunities for management of this disease we have carried out polysome profiling to define the MpM translatome. We show that in MpM there is a selective increase in the translation of mRNAs encoding proteins required for ribosome assembly and mitochondrial biogenesis. This results in an enhanced rate of mRNA translation, abnormal mitochondrial morphology and oxygen consumption, and a reprogramming of metabolic outputs. These alterations delimit the cellular capacity for protein biosynthesis, accelerate growth and drive disease progression. Importantly, we show that inhibition of mRNA translation, particularly through combined pharmacological targeting of mTORC1 and 2, reverses these changes and inhibits malignant cell growth in vitro and in ex-vivo tumour tissue from patients with end-stage disease. Critically, we show that these pharmacological interventions prolong survival in animal models of asbestos-induced mesothelioma, providing the basis for a targeted, viable therapeutic option for patients with this incurable disease.
CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells
Authors: Boutin J. , Rosier J. , Cappellen D. , Prat F. , Toutain J. , Pennamen P. , Bouron J. , Rooryck C. , Merlio J. P. , Lamrissi-Garcia I. , Cullot G. , Amintas S. , Guyonnet-Duperat V. , Ged C. , Blouin J. M. , Richard E. , Dabernat S. , Moreau-Gaudry F. , Bedel A. 
Published: August 2021

AbstractCRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers.