scholarly journals Lyl-1 marks and regulates primitive macrophages and microglia development

2020 ◽  
Author(s):  
Shoutang Wang ◽  
Deshan Ren ◽  
Anna-Lila Kaushik ◽  
Gabriel Matherat ◽  
Yann Lécluse ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Yolk Sac ◽  
Haematopoietic Stem Cell ◽  
Bhlh Transcription Factor ◽  
List Type ◽  
Embryonic Patterning ◽  
Embryo Patterning ◽  
Expression Of Genes ◽  
Key Points ◽  
Brain Macrophage

AbstractDuring ontogeny, resident macrophages (MΦs) of the nervous system emerge from haematopoietic stem cell-independent progenitors originating in the Yolk Sac (YS), so that factors impairing YS MΦ development may lead to neurodevelopmental disorders resulting from defective brain resident MΦ.Here we show that Lyl-1, a bHLH transcription factor related to Scl/Tal-1, marks primitive macrophage (MΦPrim) progenitors in the YS. Transcriptomic analysis of YS MΦ progenitors indicated that MΦPrim progenitors present at embryonic day (E) 9 are clearly distinct from those present at E10. Lyl-1 bHLH disruption led to an increased production and a defective differentiation of MΦPrim progenitors. These differentiation defects were associated with profound modifications of the expression of genes involved in embryonic patterning and neurodevelopment. They also induced a reduced production of mature MΦ/microglia in the early brain, as well as a transient reduction of the microglia pool at midgestation and in the new-born.We thus identify Lyl-1 as a critical regulator of MΦPrim and microglia development, which disruption may impair organogenesis, including neurodevelopment processes.Key pointsLyl-1 expression marks yolk sac macrophages and brain macrophage/microglia/BAM.Lyl-1 deficiency impairs primitive macrophage development and leads to the up-regulation of genes involved in embryo patterning.Lyl-1-expressing primitive macrophages have an immuno-modulatory phenotype.Lyl-1 deficiency impairs microglia development and the expression of genes involved in neuro-development.

scholarly journals Transcriptomic Analysis of Short-Term Salt-Stress Response in Mega Hybrid Rice Seedlings

Agronomy ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1328
Author(s):  
Noushin Jahan ◽  
Yang Lv ◽  
Mengqiu Song ◽  
Yu Zhang ◽  
Liangguang Shang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Molecular Mechanisms ◽  
Oryza Sativa L ◽  
Transcriptome Profiling ◽  
Bhlh Transcription Factor ◽  
F1 Hybrid ◽  
Salt Stress Response ◽  
Productivity Losses ◽  
Expression Of Genes ◽  
Trait Locus

Salinity is a major abiotic stressor that leads to productivity losses in rice (Oryza sativa L.). In this study, transcriptome profiling and heterosis-related genes were analyzed by ribonucleic acid sequencing (RNA-Seq) in seedlings of a mega rice hybrid, Liang-You-Pei-Jiu (LYP9), and its two parents 93–11 and Pei-ai64s (PA64s), under control and two different salinity levels, where we found 8292, 8037, and 631 salt-induced differentially expressed genes (DEGs), respectively. Heterosis-related DEGs were obtained higher after 14 days of salt treatment than after 7 days. There were 631 and 4237 salt-induced DEGs related to heterosis under 7-day and 14-day salt stresses, respectively. Gene functional classification showed the expression of genes involved in photosynthesis activity after 7-day stress treatment, and in metabolic and catabolic activity after 14 days. In addition, we correlated the concurrence of an expression of DEGs for the bHLH transcription factor and a shoot length/salinity-related quantitative trait locus qSL7 that we fine-mapped previously, providing a confirmed case of heterosis-related genes. This experiment reveals the transcriptomic divergence of the rice F1 hybrid and its parental lines under control and salt stress state, and enlightens about the significant molecular mechanisms developed over time in response to salt stress.

scholarly journals Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 2902-2913 ◽  
Author(s):  
Athina Mylona ◽  
Charlotte Andrieu-Soler ◽  
Supat Thongjuea ◽  
Andrea Martella ◽  
Eric Soler ◽  
...  
Keyword(s):  
Early Development ◽  
Yolk Sac ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Key Points ◽  
Differentiation Block ◽  
Early Developmental

Key Points Lack of yolk-sac hematopoiesis in the Ldb1−/− mouse results from a decreased number of hemangioblasts and a differentiation block. Identification of genes and pathways regulated by Ldb1 in the hemangioblast reveals potential targets for early developmental manipulation.

scholarly journals Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study

2021 ◽  
Author(s):  
Florence Canouï-Poitrine ◽  
Antoine Rachas ◽  
Martine Thomas ◽  
Laure Carcaillon-Bentata ◽  
Roméo Fontaine ◽  
...  
Keyword(s):  
Nursing Home ◽  
General Population ◽  
Excess Mortality ◽  
Nursing Home Residents ◽  
Primary Objective ◽  
List Type ◽  
Key Points ◽  
Standardized Mortality Ratios ◽  
Using Data ◽  
Excess Deaths

AbstractImportanceNursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented.ObjectivesThe primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present.DesignWe studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System).Main outcome and measuresThe main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated.ResultThere were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563).ConclusionNH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.Key pointsDuring the first wave of the COVID-19 pandemic in France, the mortality among nursing home residents increased by 43%.Nursing home residents accounted for 51% of the total excess deaths in France.The excess mortality was higher among younger residents than among older residents.The excess mortality was higher among males than among females.We did not observe a harvesting effect during the study period (ending on August 30th, 2020, i.e., three months after the end of the first wave).

scholarly journals Mapping densely distributed membrane receptors in blood platelets with expansion microscopy

2021 ◽  
Author(s):  
Hannah S. Heil ◽  
Max Aigner ◽  
Sophia Maier ◽  
Vanessa Göb ◽  
Charly Kusch ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Super Resolution ◽  
Membrane Receptors ◽  
List Type ◽  
Platelet Receptor ◽  
Key Points ◽  
Major Vessel ◽  
Integrin Clustering ◽  
Receptor Interactions ◽  
3D Scenarios

AbstractInterrogating small platelets and their densely packed, highly abundant receptor landscape is key to understand platelet clotting. Blot clots can save lives when stopping blood loss after an injury, but also kill when blocking a major vessel. The highly abundant and densely distributed GPIIb/IIIa receptors are one reason why the underlying key distributions and interactions, in particular the relevance of integrin clustering, are not fully understood. Such dense receptor scenarios are difficult to assess even by super-resolution fluorescence microscopy. Here, we quantify various receptor interactions, and demonstrate that expansion microscopy can pinpoint such challenging interactions where conventional methods fail in such dense 3D scenarios with highly abundant receptors. We successfully combine dual-color expansion and confocal microscopy with colocalization analysis and assess platelet receptor organization without the need of a super-resolution microscope. We reveal that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets – a pattern that orchestrates platelet clotting. We show that 4x expansion is most straight-forward for platelet imaging, while 10x expansion provides highest precision which turned out to be absolutely necessary for the most difficult of the scenarios described here.Graphical AbstractNonstandard Abbreviations and AcronymsGPIX: glycoprotein IXExM: expansion microscopyKey PointsMapping of the very dense, highly abundant platelet receptor landscape requires 10x Expansion MicroscopyExM reveals that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets.

scholarly journals Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function

Blood ◽  
2013 ◽  
Vol 121 (25) ◽  
pp. 5015-5024 ◽  
Author(s):  
Sarah J. Stein ◽  
Albert S. Baldwin
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Lineage Commitment ◽  
Key Factors ◽  
Cell Homeostasis ◽  
Hematopoietic Stem ◽  
Expression Of Genes ◽  
Key Points ◽  
Genes Encoding

Key Points p65 is an important factor in hematopoiesis through the regulation of hematopoietic stem cell function and lineage commitment. p65 controls the expression of genes encoding key factors that promote hematopoietic stem cell homeostasis.

scholarly journals Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

Breathe ◽  
2016 ◽  
Vol 12 (2) ◽  
pp. 120-129 ◽  
Author(s):  
Julie Depiazzi ◽  
Mark L. Everard
Keyword(s):  
Drug Therapy ◽  
Cardiopulmonary Exercise Testing ◽  
Cost Effective ◽  
List Type ◽  
Accurate Assessment ◽  
Key Points ◽  
Physiological Limit ◽  
Young Subjects ◽  
Dysfunctional Breathing ◽  
Exercise Induced

Key pointsExcessive exercise-induced shortness of breath is a common complaint. For some, exercise-induced bronchoconstriction is the primary cause and for a small minority there may be an alternative organic pathology. However for many, the cause will be simply reaching their physiological limit or be due to a functional form of dysfunctional breathing, neither of which require drug therapy.The physiological limit category includes deconditioned individuals, such as those who have been through intensive care and require rehabilitation, as well as the unfit and the fit competitive athlete who has reached their limit with both of these latter groups requiring explanation and advice.Dysfunctional breathing is an umbrella term for an alteration in the normal biomechanical patterns of breathing that result in intermittent or chronic symptoms, which may be respiratory and/or nonrespiratory. This alteration may be due to structural causes or, much more commonly, be functional as exemplified by thoracic pattern disordered breathing (PDB) and extrathoracic paradoxical vocal fold motion disorder (pVFMD).Careful history and examination together with spirometry may identify those likely to have PDB and/or pVFMD. Where there is doubt about aetiology, cardiopulmonary exercise testing may be required to identify the deconditioned, unfit or fit individual reaching their physiological limit and PDB, while continuous laryngoscopy during exercise is increasingly becoming the benchmark for assessing extrathoracic causes.Accurate assessment and diagnosis can prevent excessive use of drug therapy and result in effective management of the cause of the individual’s complaint through cost-effective approaches such as reassurance, advice, breathing retraining and vocal exercises.This review provides an overview of the spectrum of conditions that can present as exercise-­induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual’s symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists.

scholarly journals neoepiscopeimproves neoepitope prediction with multi-variant phasing

2018 ◽  
Author(s):  
Mary A. Wood ◽  
Austin Nguyen ◽  
Adam Struck ◽  
Kyle Ellrott ◽  
Abhinav Nellore ◽  
...  
Keyword(s):  
False Negative ◽  
List Type ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Somatic Variant ◽  
Prediction Tools ◽  
Negative Results ◽  
Multiple Datasets ◽  
False Negative Results ◽  
Key Points

ABSTRACTThe vast majority of tools for neoepitope prediction from DNA sequencing of complementary tumor and normal patient samples do not consider germline context or the potential for co-occurrence of two or more somatic variants on the same mRNA transcript. Without consideration of these phenomena, existing approaches are likely to produce both false positive and false negative results, resulting in an inaccurate and incomplete picture of the cancer neoepitope landscape. We developedneoepiscopechiefly to address this issue for single nucleotide variants (SNVs) and insertions/deletions (indels), and herein illustrate how germline and somatic variant phasing affects neoepitope prediction across multiple datasets. We estimate that up to ∼5% of neoepitopes arising from SNVs and indels may require variant phasing for their accurate assessment.neoepiscopeis performant, flexible, and supports several major histocompatibility complex binding affinity prediction tools. We have releasedneoepiscopeas open-source software (MIT license,https://github.com/pdxgx/neoepiscope) for broad use.KEY POINTSGermline context and somatic variant phasing are important for neoepitope predictionMany popular neoepitope prediction tools have issues of performance and reproducibilityWe describe and provide performant software for accurate neoepitope prediction from DNA-seq data

scholarly journals Characterizing the zebrafish organizer: microsurgical analysis at the early-shield stage

Development ◽  
1996 ◽  
Vol 122 (4) ◽  
pp. 1313-1322 ◽  
Author(s):  
J. Shih ◽  
S.E. Fraser
Keyword(s):  
Neural Development ◽  
Neural Induction ◽  
Leading Edge ◽  
Axis Formation ◽  
Embryonic Patterning ◽  
Fish Embryo ◽  
Embryo Patterning ◽  
Embryonic Shield ◽  
Microsurgical Techniques ◽  
Notochord Cells

The appearance of the embryonic shield, a slight thickening at the leading edge of the blastoderm during the formation of the germ ring, is one of the first signs of dorsoventral polarity in the zebrafish embryo. It has been proposed that the shield plays a role in fish embryo patterning similar to that attributed to the amphibian dorsal lip. In a recent study, we fate mapped many of the cells in the region of the forming embryonic shield, and found that neural and mesodermal progenitors are intermingled (Shih, J. and Fraser, S.E. (1995) Development 121, 2755–2765), in contrast to the coherent region of mesodermal progenitors found at the amphibian dorsal lip. Here, we examine the fate and the inductive potential of the embryonic shield to determine if the intermingling reflects a different mode of embryonic patterning than that found in amphibians. Using the microsurgical techniques commonly used in amphibian and avian experimental embryology, we either grafted or deleted the region of the embryonic shield. Homotopic grafting experiments confirmed the fates of cells within the embryonic shield region, showing descendants in the hatching gland, head mesoderm, notochord, somitic mesoderm, endoderm and ventral aspect of the neuraxis. Heterotopic grafting experiments demonstrated that the embryonic shield can organize a second embryonic axis; however, contrary to our expectations based on amphibian research, the graft contributes extensively to the ectopic neuraxis. Microsurgical deletion of the embryonic shield region at the onset of germ ring formation has little effect on neural development: embryos with a well-formed and well-patterned neuraxis develop in the complete absence of notochord cells. While these results show that the embryonic shield is sufficient for ectopic axis formation, they also raise questions concerning the necessity of the shield region for neural induction and embryonic patterning after the formation of the germ ring.

scholarly journals CyTOF reveals phenotypically-distinct human blood neutrophil populations differentially correlated with melanoma stage

2019 ◽  
Author(s):  
Yanfang Peipei Zhu ◽  
Tobias Eggert ◽  
Daniel J. Araujo ◽  
Pandurangan Vijayanand ◽  
Christian H. Ottensmeier ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Disease Stage ◽  
Positive Trend ◽  
List Type ◽  
Functional Evaluation ◽  
Blood Neutrophil ◽  
Key Points ◽  
Treatment Naïve ◽  
Melanoma Patients

ABSTRACTUnderstanding neutrophil heterogeneity and its relationship to disease progression has become a recent focus of cancer research. Indeed, several studies have identified neutrophil subpopulations associated with pro- or anti-tumoral functions. However, this work has been hindered by the lack of widely-accepted markers with which to define neutrophil subpopulations. To identify markers of neutrophil heterogeneity in cancer, we utilized single-cell cytometry by time-of-flight (CyTOF) coupled with high-dimensional analysis on blood samples from treatment-naïve, melanoma patients. Our efforts allowed us to identify 7 blood-neutrophil clusters, including 2 previously identified individual populations. Interrogation of these neutrophil subpopulations revealed a positive trend between specific clusters and disease stage. Finally, we recapitulated these 7 blood-neutrophil populations via flow cytometry and found that they exhibit diverse capacities for phagocytosis and reactive oxygen species (ROS) production in vitro. In summary, our data provide a refined consensus on neutrophil-heterogeneity markers, enabling a prospective functional evaluation in patients with solid tumors.KEY POINTSCyTOF analysis reveals 7 blood neutrophil clusters correlating with melanoma stage in treatment-naïve patients.Neutrophil clusters by unbiased-calling are recapitulated by flow cytometry and harbor diverse phagocytic and ROS-producing capacities.

scholarly journals Re-assembly, quality evaluation, and annotation of 678 microbial eukaryotic reference transcriptomes

2018 ◽  
Author(s):  
Lisa K. Johnson ◽  
Harriet Alexander ◽  
C. Titus Brown
Keyword(s):  
De Novo ◽  
Open Reading Frames ◽  
List Type ◽  
Accurate Identification ◽  
Sequencing Project ◽  
Large Sets ◽  
Rnaseq Data ◽  
Key Points ◽  
Computationally Intensive ◽  
Reading Frames

AbstractBackgroundDe novo transcriptome assemblies are required prior to analyzing RNAseq data from a species without an existing reference genome or transcriptome. Despite the prevalence of transcriptomic studies, the effects of using different workflows, or “pipelines”, on the resulting assemblies are poorly understood. Here, a pipeline was programmatically automated and used to assemble and annotate raw transcriptomic short read data collected by the Marine Microbial Eukaryotic Transcriptome Sequencing Project (MMETSP). The resulting transcriptome assemblies were evaluated and compared against assemblies that were previously generated with a different pipeline developed by the National Center for Genome Research (NCGR).ResultsNew transcriptome assemblies contained the majority of previous contigs as well as new content. On average, 7.8% of the annotated contigs in the new assemblies were novel gene names not found in the previous assemblies. Taxonomic trends were observed in the assembly metrics, with assemblies from the Dinoflagellata and Ciliophora phyla showing a higher percentage of open reading frames and number of contigs than transcriptomes from other phyla.ConclusionsGiven current bioinformatics approaches, there is no single ‘best’ reference transcriptome for a particular set of raw data. As the optimum transcriptome is a moving target, improving (or not) with new tools and approaches, automated and programmable pipelines are invaluable for managing the computationally-intensive tasks required for re-processing large sets of samples with revised pipelines and ensuring a common evaluation workflow is applied to all samples. Thus, re-assembling existing data with new tools using automated and programmable pipelines may yield more accurate identification of taxon-specific trends across samples in addition to novel and useful products for the community.Key PointsRe-assembly with new tools can yield new resultsAutomated and programmable pipelines can be used to process arbitrarily many samples.Analyzing many samples using a common pipeline identifies taxon-specific trends.

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