bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative model of plant gravitropism linking statoliths position and auxin transport
Authors: Levernier Nicolas , Pouliquen Olivier , Forterre Yoël 
Published: January 2021

ABSTRACTGravity is a major cue for the proper growth and development of plants. The response of plants to gravity implies starch-filled plastids, the statoliths, which sediments at the bottom of the gravisensing cells, the statocytes. Statoliths are assumed to modify the transport of the growth hormone, auxin, by acting on specific auxin transporters, PIN proteins. However, the complete gravitropic signaling pathway from the intracellular signal associated to statoliths to the plant bending is still not well understood. In this article, we build on recent experimental results showing that statoliths do not act as gravitational force sensor, but as position sensor, to develop a bottom-up theory of plant gravitropism. The main hypothesis of the model is that the presence of statoliths modifies PIN trafficking close to the cell membrane. This basic assumption, coupled with auxin transport and growth in an idealized tissue made of a one-dimensional array of cells, recovers several major features of the gravitropic response of plants. First, the model provides a new interpretation for the response of a plant to a steady stimulus, the so-called sine-law of plant gravitropism. Second, it predicts the existence of a gravity-independent memory process as observed recently in experiments studying the response to transient stimulus. The model suggests that the timescale of this process is associated to PIN turnover, calling for new experimental studies.
Degradation of Photoreceptor Outer Segments by the Retinal Pigment Epithelium Requires Pigment Epithelium-derived Factor Receptor (PEDF-R)
Authors: Bullock Jeanee , Polato Federica , Abu-Asab Mones , Bernardo-Colón Alexandra , Aflaki Elma , Agbaga Martin-Paul , Becerra S. Patricia 
Published: January 2021

AbstractPurposeTo examine the contribution of PEDF-R to the phagocytosis process. Previously, we identified PEDF-R, the protein encoded by thePNPLA2gene, as a phospholipase A2 in the retinal pigment epithelium (RPE). During phagocytosis, RPE cells ingest abundant phospholipids and protein in the form of photoreceptor outer segment (POS) tips, which are then hydrolyzed. The role of PEDF-R in RPE phagocytosis is not known.MethodsMice in whichPNPLA2was conditionally knocked out in the RPE were generated (cKO). Mouse RPE/choroid explants were cultured. Human ARPE-19 cells were transfected with siPNPLA2silencing duplexes. POS were isolated from bovine retinas. The phospholipase A2 inhibitor bromoenol lactone was used. Transmission electron microscopy, immunofluorescence, lipid labeling, pulse-chase experiments, western blots, and free fatty acid and β-hydroxybutyrate assays were performed.ResultsThe RPE of the cKO mice accumulated lipids as well as more abundant and larger rhodopsin particles compared to littermate controls. Upon POS exposure, RPE explants from cKO mice released less β-hydroxybutyrate compared to controls. After POS ingestion during phagocytosis, rhodopsin degradation was stalled both in cells treated with bromoenol lactone and inPNPLA2-knocked-down cells relative to their corresponding controls. Phospholipase A2 inhibition lowered β-hydroxybutyrate release from phagocytic RPE cells.PNPLA2knock down also resulted in a decline in fatty acids and β-hydroxybutyrate release from phagocytic RPE cells.ConclusionsPEDF-R downregulation delayed POS digestion during phagocytosis. The findings imply that efficiency of RPE phagocytosis depends on PEDF-R, thus identifying a novel contribution of this protein to POS degradation in the RPE.
Long term consumption of green tea EGCG enhances healthspan and lifespan in mice by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis and immunosenescence
Authors: Sharma Rohit , Kumar Ravi , Sharma Anamika , Goel Abhishek , Padwad Yogendra 
Published: January 2021

AbstractCellular senescence is emerging as the causal nexus of aging, and its potential modulators present an effective strategy to counter age-related morbidity. The current study profiled the extent of cellular senescence in different organs of mice at four different time-points of lifespan, and explored the influence of epigallocatechin gallate (EGCG) consumption in impacting multiple aspects of aging biology. We report that adipose and intestinal tissues are highly vulnerable to cellular senescence as evident by age-associated increase in DNA damage response, activation of cell cycle inhibitors (p53/p21) and induction of SASP (p38MAPK/NF-κB/Cox-2). Further, a distinct modulation of nutrient signaling pathway mediators (AMPK/Akt/SIRT3 and 5), and a decrease in autophagy effectors was also observed in aging animals. Systemic inflamm-aging markers (TNF-α/IL-lβ) and splenic CD4/CD8 ratio increased with age, while NK cell population decreased. Metagenomic analyses revealed age-related decrease in the diversity of microbial species while an increase in the abundance of various pathogenic bacterial genera was also observed. Long term EGCG consumption enhanced lifespan of animals by attenuating markers of DNA damage, cell cycle inhibitors and SASP in adipose, intestine and liver tissue. Mechanistically, EGCG inhibited the activation of AMPK and Akt and enhanced mitochondrial SIRT3 and SIRT5 expression, as well as autophagic response in adipose and intestinal tissues. Systemic presence of inflamm-aging markers decreased while expression of T cell immune response regulator CD69 increased in EGCG fed animals. EGCG also improved age-related decrease in the diversity of microbial species and suppressed the growth of pathogenic microbes. In short, our results provide compelling evidence that post-mitotic adipose tissue is a major site of cellular senescence and SASP activation, and that chronic EGCG consumption can influence several aspects of aging and senescence resulting in improved organismal healthspan and lifespan.
12-Lipoxygenase Governs the Innate Immune Pathogenesis of Islet Inflammation and Autoimmune Diabetes
Authors: Kulkarni Abhishek , Pineros Annie R. , Ibrahim Sara , Hernandez-Perez Marimar , Orr Kara S. , Glenn Lindsey , Walsh Melissa , Nadler Jerry L. , Morris Margaret A. , Tersey Sarah A. , Mirmira Raghavendra G. , Anderson Ryan M. 
Published: January 2021

ABSTRACTMacrophages and related myeloid cells are innate immune cells that participate in the early islet inflammation of type 1 diabetes (T1D). The inflammatory signals and antigen presentation by these cells may be inducers of the adaptive immune response that is the hallmark of T1D. The enzyme 12-lipoxygenase (12-LOX) catalyzes the formation of pro-inflammatory eicosanoids from membrane-derived phospholipids, but its role and mechanisms in the pathogenesis of islet inflammation have not been elucidated. Leveraging a model of T1D-like islet inflammation in zebrafish, we show here that macrophages contribute significantly to the loss of β-cells and the subsequent development of hyperglycemia. Depletion or inhibition of 12-LOX in this model resulted in significantly reduced macrophage infiltration into islets with preservation of β-cell mass. In mice, we deleted the gene encoding 12-LOX (Alox15) in the myeloid lineage in the non-obese diabetic (NOD) model of T1D. Myeloid cell-specificAlox15knockout NOD mice demonstrated reduced insulitis and T-cell responses, preserved β cell mass, and almost complete protection from the development of T1D. A critical effect of 12-LOX depletion appeared secondary to a defect in myeloid cell migration, a function required for immune surveillance and tissue injury responses. This effect on migration appeared to be secondary to the loss of the chemokine receptor CXCR3. Transgenic expression of the gene encoding CXCR3 rescued the migrator defect in zebrafish 12-LOX morphants. Taken together, our results reveal a formative role for innate immune myeloid cells in the early pathogenesis of T1D and identify 12-LOX as a necessary enzyme to promote their pro-diabetogenic phenotype in the context of autoimmunity.
Transcriptomic profiling uncovers novel players in innate immunity inArabidopsis thaliana
Authors: Safaeizadeh Mehdi , Boller Thomas , Becker Claude 
Published: January 2021

AbstractIn this research a high-throughput RNA sequencing based transcriptome analysis technique (RNA-Seq) was used to evaluate differentially expressed genes (DEGs) in the wild type Arabidopsis seedling in response to flg22, a well-known microbe-associated molecular pattern (MAMP), andAtPep1, a well-known peptide representing an endogenous damage-associated molecular patterns (DAMP). The results of our study revealed that 1895 (1634 up-regulated and 261 down-regulated) and 2271 (1706 up-regulated and 565 down-regulated) significant differentially expressed genes in response to flg22 andAtPep1 treatment, respectively. Among significant DEGs, we observed that a number of hitherto overlooked genes have been found to be induced upon treatment with either flg22 or withAtPep1, indicating their possible involvement in innate immunity. Here, we characterized two of them, namely PP2-B13 and ACLP1.pp2-b13andaclp1mutants showed an increased susceptibility to infection by the virulent pathogenPseudomomas syringae pv tomato mutant hrcC-, as evidenced by an increased growth of the pathogen in planta. Further we present evidence that theaclp1mutant was deficient in ethylene production upon flg22 treatment, while thepp2-b13mutant, was deficient in ROS production. The results from this research provide new information to a better understanding of the immune system in Arabidopsis.
The steroid-inducible pOp6/LhGR gene expression system is fast, sensitive and does NOT cause plant growth defects in rice (Oryza sativa)
Authors: Samalova Marketa , Moore Ian 
Published: January 2021

SummaryInducible systems for transgene expression activated by a chemical inducer or an inducer of non-plant origin are desirable tools for both basic plant research and biotechnology. Although, the technology has been widely exploited in model plants, it has not been optimised for use with the major monocotyledonous crop species, namely rice. We have adapted the dexamethasone-inducible pOp6/LhGR system for rice and shown that it is fast, sensitive and tightly regulated, with high levels of induction that remain stable over several generations. Most importantly, we have shown that the system does not cause negative growth defectsin vitroor in soil grown plants. Interestingly in the process of testing, we found that another steroid, triamcinolone acetonide, is a more potent inducer in rice than dexamethasone. We present serious considerations for the construct design to avoid undesirable effects caused by the system in plants, leakiness and possible silencing, as well as simple steps how to maximize translation efficiency of a gene of interest. Finally, we compare the performance of the pOp6/LhGR system with other chemically inducible systems tested in rice in terms of the properties of an ideal inducible system.Significance statementThe non-monocot codon-optimized version of the dexamethasone inducible pOp6/LhGR system does not cause severe developmental perturbations in rice plants.
Mapping the temporal and spatial dynamics of the human endometriumin vivoandin vitro
Authors: Garcia-Alonso Luz , Handfield Louis-François , Roberts Kenny , Nikolakopoulou Konstantina , Fernando Ridma C. , Gardner Lucy , Woodhams Ben , Arutyunyan Anna , Polanski Krzysztof , Hoo Regina , Sancho-Serra Carmen , Li Tong , Kwakwa Kwasi , Tuck Elizabeth , Kleshchevnikov Vitalii , Tarkowska Aleksandra , Porter Tarryn , Mazzeo Cecilia Icoresi , van Dongen Stijn , Dabrowska Monika , Vaskivskyi Vasyl , Mahbubani Krishna T. , Park Jong-eun , Jimenez-Linan Mercedes , Campos Lia , Kiselev Vladimir , Lindskog Cecilia , Ayuk Paul , Prigmore Elena , Stratton Michael R , Saeb-Parsy Kourosh , Moffett Ashley , Moore Luiza , Bayraktar Omer A. , Teichmann Sarah A. , Turco Margherita Y. , Vento-Tormo Roser 
Published: January 2021

AbstractThe endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineagein vivoandin vitro. We showin vitrothat downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.
Measurement of curvature and twist of microtubule bundles in the mitotic spindle
Authors: Ivec Arian , Trupinić Monika , Tolić Iva M. , Pavin Nenad 
Published: January 2021

AbstractThe highly ordered spatial organization of microtubule bundles in the mitotic spindle is crucial for its proper functioning. The recent discovery of twisted shapes of microtubule bundles and spindle chirality suggests that the bundles extend along curved paths in three dimensions, rather than being confined to a plane. This in turn implies that rotational forces exist in the spindle in addition to the widely studied linear forces. However, studies of spindle architecture and forces are impeded by a lack of a robust method for the geometric quantification of microtubule bundles in the spindle. In this paper, we describe a simple method for measuring and evaluating the shapes of microtubule bundles, by characterizing them in terms of their curvature and twist. By using confocal microscopy, we obtain three-dimensional images of spindles, which allow us to trace the entire microtubule bundles. For each traced bundle, we first fit a plane, and then fit a circle lying in that plane. With this easily reproducible method, we extract the curvature and twist, which represent the geometric information characteristic for each bundle. As the bundle shapes reflect the forces within them, this method is valuable for the understanding of forces that act on chromosomes during mitosis.
Massively parallel characterization of engineered transcript isoforms using direct RNA sequencing
Authors: Tarnowski Matthew J. , Gorochowski Thomas E. 
Published: January 2021

AbstractTranscriptional terminators signal where transcribing RNA polymerases (RNAPs) should halt and disassociate from DNA. However, because termination is stochastic, two different forms of transcript could be produced: one ending at the terminator and the other reading through. An ability to control the abundance of these transcript isoforms would offer bioengineers a mechanism to regulate multi-gene constructs at the level of transcription. Here, we explore this possibility by repurposing terminators as ‘transcriptional valves’ which can tune the proportion of RNAP read-through. Using one-pot combinatorial DNA assembly we construct 1183 transcriptional valves for T7 RNAP and show how nanopore-based direct RNA sequencing (dRNA-seq) can be used to simultaneously characterize the entire pool at a nucleotide resolutionin vitroand unravel genetic design principles to tune and insulate their function using nearby sequence context. This work provides new avenues for controlling transcription and demonstrates the value of long-read sequencing for exploring complex sequence-function landscapes.
The Dorsolateral Prefrontal Cortex Presents Structural Variations Associated with Empathic Capacity in Psychotherapists
Authors: Domínguez-Arriola Marcos E. , Olalde-Mathieu Víctor E. , Garza-Villareal Eduardo A. , Barrios Fernando A. 
Published: January 2021

AbstractEmpathic capacity has been shown to be correlated with brain structural variations, such as cortical thickness. Since psychotherapists have a constant demand to modulate their empathic response, in this study we compared cortical thickness between a group of psychotherapists and a control group at prefrontal and cingulate brain regions, and investigated how this is correlated with their empathic skills. Eighteen psychotherapists and eighteen healthy controls underwent 3-Tesla MRI scanning and completed empathy-related psychometric assessments. Cortical thickness (CT) measures were estimated for each participant. We evaluated how these measures differed between groups, and if they were associated with individual empathy-related scores in a series of regions of interest. Our analysis shows that psychotherapists display a significantly greater CT at a region in the left dorsolateral prefrontal cortex (dlPFC; p < 0.05, FDR corrected). Moreover, psychotherapists’ CT in this region is correlated with the tendency to feel empathically concerned for others (p < 0.01, FDR corrected). This finding is relevant because the dlPFC region participates strongly in the cognitive components of the empathic response, such as emotion regulation and perspective-taking processes. Thus, our findings support the idea that empathic capacity is reflected by brain structural variations while also studying for the first time a sample of subjects for whom empathic responding is crucial in their profession.
Deep learning driven quantification of interstitial fibrosis in kidney biopsies
Authors: Zheng Yi , Cassol Clarissa A. , Jung Saemi , Veerapaneni Divya , Chitalia Vipul C. , Ren Kevin , Bellur Shubha S. , Boor Peter , Barisoni Laura M. , Waikar Sushrut S. , Betke Margrit , Kolachalama Vijaya B. 
Published: January 2021

AbstractInterstitial fibrosis and tubular atrophy (IFTA) on a renal biopsy are strong indicators of disease chronicity and prognosis. Techniques that are typically used for IFTA grading remain manual, leading to variability among pathologists. Accurate IFTA estimation using computational techniques can reduce this variability and provide quantitative assessment by capturing the pathologic features. Using trichrome-stained whole slide images (WSIs) processed from human renal biopsies, we developed a deep learning (DL) framework that captured finer pathological structures at high resolution and overall context at the WSI-level to predict IFTA grade. WSIs (n=67) were obtained from The Ohio State University Wexner Medical Center (OSUWMC). Five nephropathologists independently reviewed them and provided fibrosis scores that were converted to IFTA grades: <=10% (None or minimal), 11-25% (Mild), 26-50% (Moderate), and >50% (Severe). The model was developed by associating the WSIs with the IFTA grade determined by majority voting (reference estimate). Model performance was evaluated on WSIs (n=28) obtained from the Kidney Precision Medicine Project (KPMP). There was good agreement on the IFTA grading between the pathologists and the reference estimate (Kappa=0.622±0.071). The accuracy of the DL model was 71.8±5.3% on OSUWMC and 65.0±4.2% on KPMP datasets, respectively. Identification of salient image regions by combining microscopic and WSI-level pathological features yielded visual representations that were consistent with the pathologist-based IFTA grading. Our approach to analyzing microscopic- and WSI-level changes in renal biopsies attempts to mimic the pathologist and provides a regional and contextual estimation of IFTA. Such methods can assist clinicopathologic diagnosis.Translational statementPathologists rely on interstitial fibrosis and tubular atrophy (IFTA) to indicate chronicity in kidney biopsies and provide a prognostic indicator of renal survival. Although guidelines for evaluation of IFTA exist, there is variability in IFTA estimation among pathologists. In this work, digitized kidney biopsies were independently reviewed by five nephropathologists and majority voting on their ratings was used to determine the IFTA grade. Using this information, a deep learning model was developed that captured microscopic and holistic features on the digitized biopsies and accurately predicted the IFTA grade. The study illustrates that deep learning can be utilized effectively to perform IFTA grading, thus enhancing conventional clinicopathologic diagnosis.
The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children
Authors: Hachim Asmaa , Gu Haogao , Kavian Otared , Kwan Mike YW , Chan Wai-hung , Yau Yat Sun , Chiu Susan S , Tsang Owen TY , Hui David SC , Ma Fionn , Lau Eric HY , Cheng Samuel MS , Poon Leo LM , Peiris JS Malik , Valkenburg Sophie A , Kavian Niloufar 
Published: January 2021

AbstractBackgroundChildren are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.MethodsWe tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).FindingsChildren have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.