bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila
Authors: Takakura Mai , Nakagawa Reiko , Ota Takeshi , Kimura Yoko , NG Man Yung , Alia Abdalla G. , Okuno Hiroyuki , Hirano Yukinori 
Published: January 2021

AbstractConsolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.
Murine liver repair via transient activation of regenerative pathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified mRNA
Authors: Rizvi Fatima , Everton Elissa , Smith Anna R. , Liu Hua , Osota Elizabeth , Beattie Mitchell , Tam Ying , Pardi Norbert , Weissman Drew , Gouon-Evans Valerie 
Published: January 2021

AbstractInduction of intrinsic liver regeneration is an unmet need that can be achieved by temporally activating key hepatocyte regenerative pathways. Here, we establish an efficient, safe, non-integrative method to transiently express hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF) in hepatocytes via nucleoside-modified, lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) delivery in mice. We confirm specific hepatotropism of mRNA-LNP via intravenous injection of firefly luciferase encoding mRNA-LNP, with protein expression lasting about 3 days. In the liver, virtually all hepatocytes are transfected along with a subpopulation of endothelial and Kupffer cells. In homeostasis, HGF mRNA-LNP efficiently induce hepatocyte proliferation. In a chronic liver injury mouse model recapitulating non-alcoholic fatty liver disease, injections of both HGF and EGF mRNA-LNP sharply reverse steatosis and accelerate restoration of liver function. Likewise, HGF and EGF mRNA-LNP accelerate liver regeneration after acetaminophen-induced acute liver injury with rapid return to baseline ALT levels. This study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness liver regeneration via controlled expression of endogenous mitogens in vivo.
Desynchronized liquid crystalline network actuators with deformation reversal capability
Authors: Xiao Yao-Yu , Jiang Zhi-Chao , Hou Jun-Bo , Zhao Yue 
Published: January 2021

AbstractLiquid crystalline network (LCN) actuator normally deforms upon thermally or optically induced order-disorder phase transition, switching once between two shapes (shape 1 in LC phase and shape 2 in isotropic state) for each stimulation on/off cycle. Herein, we report an LCN actuator that deforms from shape 1 to shape 2 and then reverses the deformation direction to form shape 3 on heating or under light only, thus completing the shape switch twice for one stimulation on/off cycle. The deformation reversal capability is obtained with a monolithic LCN actuator whose two sides are made to start deforming at different temperatures and exerting different reversible strains, by means of asymmetrical crosslinking and/or asymmetrical stretching. This desynchronized actuation strategy offers possibilities in developing light-fueled LCN soft robots. In particular, the multi-stage bidirectional shape change enables multimodal, light-driven locomotion from the same LCN actuator by simply varying the light on/off times.
Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass
Authors: Lovell John T. , MacQueen Alice H. , Mamidi Sujan , Bonnette Jason , Jenkins Jerry , Napier Joseph D. , Sreedasyam Avinash , Healey Adam , Session Adam , Shu Shengqiang , Barry Kerrie , Bonos Stacy , Boston LoriBeth , Daum Christopher , Deshpande Shweta , Ewing Aren , Grabowski Paul P. , Haque Taslima , Harrison Melanie , Jiang Jiming , Kudrna Dave , Lipzen Anna , Pendergast Thomas H. , Plott Chris , Qi Peng , Saski Christopher A. , Shakirov Eugene V. , Sims David , Sharma Manoj , Sharma Rita , Stewart Ada , Singan Vasanth R. , Tang Yuhong , Thibivillier Sandra , Webber Jenell , Weng Xiaoyu , Williams Melissa , Wu Guohong Albert , Yoshinaga Yuko , Zane Matthew , Zhang Li , Zhang Jiyi , Behrman Kathrine D. , Boe Arvid R. , Fay Philip A. , Fritschi Felix B. , Jastrow Julie D. , Lloyd-Reilley John , Martínez-Reyna Juan Manuel , Matamala Roser , Mitchell Robert B. , Rouquette Francis M. , Ronald Pamela , Saha Malay , Tobias Christian M. , Udvardi Michael , Wing Rod A. , Wu Yanqi , Bartley Laura E. , Casler Michael , Devos Katrien M. , Lowry David B. , Rokhsar Daniel S. , Grimwood Jane , Juenger Thomas E. , Schmutz Jeremy 
Published: January 2021

AbstractLong-term climate change and periodic environmental extremes threaten food and fuel security1and global crop productivity2–4. Although molecular and adaptive breeding strategies can buffer the effects of climatic stress and improve crop resilience5, these approaches require sufficient knowledge of the genes that underlie productivity and adaptation6—knowledge that has been limited to a small number of well-studied model systems. Here we present the assembly and annotation of the large and complex genome of the polyploid bioenergy crop switchgrass (Panicum virgatum). Analysis of biomass and survival among 732 resequenced genotypes, which were grown across 10 common gardens that span 1,800 km of latitude, jointly revealed extensive genomic evidence of climate adaptation. Climate–gene–biomass associations were abundant but varied considerably among deeply diverged gene pools. Furthermore, we found that gene flow accelerated climate adaptation during the postglacial colonization of northern habitats through introgression of alleles from a pre-adapted northern gene pool. The polyploid nature of switchgrass also enhanced adaptive potential through the fractionation of gene function, as there was an increased level of heritable genetic diversity on the nondominant subgenome. In addition to investigating patterns of climate adaptation, the genome resources and gene–trait associations developed here provide breeders with the necessary tools to increase switchgrass yield for the sustainable production of bioenergy.
Alarming coastal vulnerability of the deltaic and sandy beaches of North Africa
Authors: Hzami Abderraouf , Heggy Essam , Amrouni Oula , Mahé Gil , Maanan Mohamed , Abdeljaouad Saâdi 
Published: January 2021

AbstractThe arid coasts of North Africa, extending over 4633 km from the Gulf of Tunis to the Nile Delta, are undergoing pronounced shoreline retreats and coastal floodings that are reported as a consequence of the ongoing sea level rise resulting from global warming. Of particular interest are the abnormal shoreline dynamics for deltaic and sandy beaches, which are severely impacted by abrupt decadal variabilities in both climatic and anthropogenic drivers resulting in their increased vulnerability to disturbances from coastal hazards. Unfortunately, the evolution, distribution and impacts of these drivers remain largely unquantified, let alone understood, for these extensive arid coasts that harbor the major portion of North Africa’s population as well as unique and fragile marine ecosystems. To address this deficiency, we use GIS-based multi-criteria approaches combined with analytic hierarchy process to map the Coastal Vulnerability Index and the Socioeconomic Vulnerability Index along these coasts to investigate the amplitude and extent of shoreline deterioration resulting from sudden fluctuations in sediment transport to the coastline. We use the western bay of the Gulf of Tunis, the coasts of Tripoli and the Nile Delta as three validation sites for our vulnerability assessment. The statistical Integrated Coastal Vulnerability Index map reveals that 47% of arid North African coasts are characterized by high to very high vulnerability. In particular, we observe that the densely populated deltaic coasts in both Tunisia and Egypt are 70% more vulnerable than any others coast in the eastern Mediterranean Basin. These abnormally high-vulnerability extensive areas are also correlated with significant deterioration of coastal aquifers and hence in crop production, compromising local food security and resulting in increasing outflow migration trends. Both Tunisia and Egypt observed dramatic increases in the net population outflow migration by respectively 62% and 248% between 2000 and 2016, mostly from coastal areas. Our source analysis of the amplitude and extent of these high coastal vulnerabilities suggests that they result from the anthropogenic drivers of damming and rapid urban growth over the last few decades rather than the effects of global warming.
Cyclophosphamide arrhythmogenicitytesting using human-induced pluripotent stem cell-derived cardiomyocytes
Authors: Podgurskaya A. D. , Slotvitsky M. M. , Tsvelaya V. A. , Frolova S. R. , Romanova S. G. , Balashov V. A. , Agladze K. I. 
Published: January 2021

AbstractCyclophosphamide (CP) is an anticancer drug, an alkylating agent. Cardiotoxicity of CP is associated with one of its metabolites, acrolein, and clinical cardiotoxicity manifestations are described for cases of taking CP in high doses. Nevertheless, modern arrhythmogenicity prediction assays in vitro include evaluation of beat rhythm and rate as well as suppression of cardiac late markers after acute exposure to CP, but not its metabolites. The mechanism of CP side effects when taken at low doses (i.e., < 100 mg/kg), especially at the cellular level, remains unclear. In this study conduction properties and cytoskeleton structure of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained from a healthy donor under CP were evaluated. Arrhythmogenicity testing including characterization of 3 values: conduction velocity, maximum capture rate (MCR) measurements and number of occasions of re-entry on a standard linear obstacle was conducted and revealed MCR decrease of 25% ± 7% under CP. Also, conductivity area reduced by 34 ± 15%. No effect of CP on voltage-gated ion channels was found. Conduction changes (MCR and conductivity area decrease) are caused by exposure time-dependent alpha-actinin disruption detected both in hiPSC-CMs and neonatal ventricular cardiomyocytes in vitro. Deviation from the external stimulus frequency and appearance of non-conductive areas in cardiac tissue under CP is potentially arrhythmogenic and could develop arrhythmic effects in vivo.
The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells
Authors: Weerasinghe Harshini , Bugeja Hayley E. , Andrianopoulos Alex 
Published: January 2021

AbstractMicrobial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.
Dendrons containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to silica-coated magnetite for the expeditious synthesis of Hantzsch esters
Authors: Sam Mahsa , Dekamin Mohammad G. , Alirezvani Zahra 
Published: January 2021

AbstractA new multifunctional dendritic nanocatalyst containing boric acid and 1,3,5-tris(2-hydroxyethyl)isocyanurate covalently attached to core–shell silica-coated magnetite (Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2) was designed and properly characterized by different spectroscopic or microscopic methods as well as analytical techniques used for mesoporous materials. It was found that the combination of both aromatic π–π stacking and boron–oxygen ligand interactions affords supramolecular arrays of dendrons. Furthermore, the use of boric acid makes this dendritic catalyst a good choice, from corrosion, recyclability and cost points of view. The catalytic activity of Fe3O4@SiO2@PTS-THEIC-(CH2)3OB(OH)2, as an efficient magnetically recoverable catalyst, was investigated for the synthesis of polyhydroacridines (PHAs) as well as polyhydroquinolines (PHQs) via one-pot multicomponent reactions of dimedone and/or ethyl acetoacetate, different aldehydes and ammonium acetate in EtOH under reflux conditions. Very low loading of the catalyst, high to quantitative yields of the desired PHAs or PHQs products, short reaction times, wide scope of the substrates, eliminating any toxic heavy metals or corrosive reagents for the modification of the catalyst, and simple work-up procedure are remarkable advantages of this green protocol. An additional advantage of this magnetic nanoparticles catalyst is its ability to be separated and recycled easily from the reaction mixture with minimal efforts in six subsequent runs without significant loss of its catalytic activity. This magnetic and dendritic catalyst can be extended to new two- and three-dimensional covalent organic frameworks with different applications.
Long-term tillage effect on with-in season variations in soil conditions and respiration from dryland winter wheat and soybean cropping systems
Authors: Zapata Diana , Rajan Nithya , Mowrer Jake , Casey Kenneth , Schnell Ronnie , Hons Frank 
Published: January 2021

AbstractSoil respiration from agricultural soils is a major anthropogenic source of CO2to the atmosphere. With-in season emission of soil CO2from croplands are affected by changes in weather, tillage, plant row spacing, and plant growth stage. Tillage involves physical turning of soils which accelerate residue decomposition and CO2emission. No-tillage lacks soil disturbance and residues undergo slower decomposition at the surface. In this study, we compared with-in season soil conditions (temperature and moisture) and soil respiration from two major crops (soybean and winter wheat) by making high temporal frequency measurements using automated chambers at half-hourly intervals. The experiment lasted for 179 days. Total number of measurements made from conventional and no-tillage soybean and winter wheat plots were 6480 and 4456, respectively. Average flux after the winter-dormancy period of wheat was 37% higher in tilled soil compared to no-till soil. However, average flux during the soybean growing season was 8% lower in conventional till compared to no-till soil. This differential response of soil respiration in wheat and soybean was primarily due to tillage-induced changes in surface characteristics (residue cover) and soil environmental conditions (soil temperature and soil moisture). Results from this study can help elucidate relationships for modeling and assessment of field-scale soil CO2emissions from dryland wheat and soybean crops grown in sub-tropics.
Classification of colorectal tissue images from high throughput tissue microarrays by ensemble deep learning methods
Authors: Nguyen Huu-Giao , Blank Annika , Dawson Heather E. , Lugli Alessandro , Zlobec Inti 
Published: January 2021

AbstractTissue microarray (TMA) core images are a treasure trove for artificial intelligence applications. However, a common problem of TMAs is multiple sectioning, which can change the content of the intended tissue core and requires re-labelling. Here, we investigate different ensemble methods for colorectal tissue classification using high-throughput TMAs. Hematoxylin and Eosin (H&E) core images of 0.6 mm or 1.0 mm diameter from three international cohorts were extracted from 54 digital slides (n = 15,150 cores). After TMA core extraction and color enhancement, five different flows of independent and ensemble deep learning were applied. Training and testing data with 2144 and 13,006 cores included three classes: tumor, normal or “other” tissue. Ground-truth data were collected from 30 ngTMA slides (n = 8689 cores). A test augmentation is applied to reduce the uncertain prediction. Predictive accuracy of the best method, namely Soft Voting Ensemble of one VGG and one CapsNet models was 0.982, 0.947 and 0.939 for normal, “other” and tumor, which outperformed to independent or ensemble learning with one base-estimator. Our high-accuracy algorithm for colorectal tissue classification in high-throughput TMAs is amenable to images from different institutions, core sizes and stain intensity. It helps to reduce error in TMA core evaluations with previously given labels.
Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death
Authors: Hoffiz Yarely C. , Castillo-Ruiz Alexandra , Hall Megan A. L. , Hite Taylor A. , Gray Jennifer M. , Cisternas Carla D. , Cortes Laura R. , Jacobs Andrew J. , Forger Nancy G. 
Published: January 2021

AbstractLong-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2–3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.
The inflammatory response induced by Pseudomonas aeruginosa in macrophages enhances apoptotic cell removal
Authors: Jäger Adriana Valeria , Arias Paula , Tribulatti Maria Virginia , Brocco Marcela Adriana , Pepe Maria Victoria , Kierbel Arlinet 
Published: January 2021

AbstractPathogens phagocytosis and the uptake of apoptotic cells (efferocytosis) are essential macrophages tasks, classically considered as mutually exclusive. Macrophages have been observed to polarize into either pro-inflammatory/microbicidal or anti-inflammatory/efferocytic phenotypes. However, macrophage functions have shown to be more complex. Furthermore, little is known about the regulation of efferocytosis under inflammatory conditions. In this study, we elucidate the modulation of the macrophage efferocytic function during an inflammatory stimulus. We find that bone marrow-derived macrophages (BMDM) are very efficient in engulfing both the bacterial pathogen Pseudomonas aeruginosa and apoptotic cells. BMDM showed a high bactericidal capacity unaffected by the concomitant presence of apoptotic material. Plasticity in macrophage programming, in response to changing environmental cues, may modulate efferocytic capability. In this work, we further show that, after phagocyting and processing Pseudomonas aeruginosa, macrophages highly increase their efferocytic capacity without affecting their phagocytic function. Moreover, we demonstrate that Pseudomonas aeruginosa enhances efferocytosis of these phagocytes through the IL-6 signaling pathway. Our results show that the inflammatory response generated by the bacterial processing enhances these macrophages’ capacity to control inflammation through an increased efferocytosis.
Epithelial and stromal remodelling following femtosecond laser–assisted stromal lenticule addition keratoplasty (SLAK) for keratoconus
Authors: Nubile Mario , Salgari Niccolò , Mehta Jodhbir S. , Calienno Roberta , Erroi Emanuele , Bondì Jessica , Lanzini Manuela , Liu Yu-Chi , Mastropasqua Leonardo 
Published: January 2021

AbstractThe purpose of this study was to evaluate corneal epithelium and stromal remodelling with anterior segment optical coherence tomography in patients who have undergone stromal lenticule addition keratoplasty (SLAK) for advanced keratoconus. This was a prospective non-comparative observational study. Fifteen eyes of 15 patients with advanced keratoconus underwent implantation with a cadaveric, donor negative meniscus-shaped intrastromal lenticule, produced with a femtosecond laser, into a stromal pocket dissected in the recipient cornea at a depth of 120 μm. Simulated keratometry, central corneal thickness (CTT), corneal thinnest point (CTP), central epithelial thickness (CET), central and peripheral lenticule thickness, anterior and posterior stromal thickness were measured. Regional central corneal epithelial thickness (CET) and variations in the inner annular area (IAT) and outer annular area (OAT) were also analysed. All parameters were measured preoperatively and 1, 3, and 6 months postoperatively. The average anterior Sim-k decreased from 59.63 ± 7.58 preoperatively to 57.19 ± 6.33 D 6 months postoperatively. CCT, CTP, CET, and OAT increased and IAT decreased significantly after 1 month. All parameters appeared unchanged at 6-months except that of OAT that further increased. Lenticule thickness was stable. In conclusion we observed that SLAK reshapes the cornea by central flattening with stromal thickening and epithelial thickness restoration.