scholarly journals Functional innovations of PIN auxin transporters mark crucial evolutionary transitions during rise of flowering plants

2020 ◽  
Vol 6 (50) ◽  
pp. eabc8895
Author(s):  
Yuzhou Zhang ◽  
Lesia Rodriguez ◽  
Lanxin Li ◽  
Xixi Zhang ◽  
Jiří Friml
Keyword(s):  
Critical Role ◽  
Cell Types ◽  
Floral Organ ◽  
Flowering Plants ◽  
Flowering Plant ◽  
Evolutionary Transitions ◽  
Coding Regions ◽  
Essential Components ◽  
Complex Architecture

Flowering plants display the highest diversity among plant species and have notably shaped terrestrial landscapes. Nonetheless, the evolutionary origin of their unprecedented morphological complexity remains largely an enigma. Here, we show that the coevolution of cis-regulatory and coding regions of PIN-FORMED (PIN) auxin transporters confined their expression to certain cell types and directed their subcellular localization to particular cell sides, which together enabled dynamic auxin gradients across tissues critical to the complex architecture of flowering plants. Extensive intraspecies and interspecies genetic complementation experiments with PINs from green alga up to flowering plant lineages showed that PIN genes underwent three subsequent, critical evolutionary innovations and thus acquired a triple function to regulate the development of three essential components of the flowering plant Arabidopsis: shoot/root, inflorescence, and floral organ. Our work highlights the critical role of functional innovations within the PIN gene family as essential prerequisites for the origin of flowering plants.

scholarly journals Rapid and sustained hematopoietic recovery in lethally irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ hematopoietic stem cells

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3758-3779 ◽  
Author(s):  
N Uchida ◽  
HL Aguila ◽  
WH Fleming ◽  
L Jerabek ◽  
IL Weissman
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Blood Cells ◽  
Critical Role ◽  
White Blood Cells ◽  
Cell Types ◽  
Dose Dependence ◽  
Hematopoietic Stem ◽  
Hematopoietic Recovery

Abstract Hematopoietic stem cells (HSCs) are believed to play a critical role in the sustained repopulation of all blood cells after bone marrow transplantation (BMT). However, understanding the role of HSCs versus other hematopoietic cells in the quantitative reconstitution of various blood cell types has awaited methods to isolate HSCs. A candidate population of mouse HSCs, Thy-1.1lo Lin-Sca-1+ cells, was isolated several years ago and, recently, this population has been shown to be the only population of BM cells that contains HSCs in C57BL/Ka-Thy-1.1 mice. As few as 100 of these cells can radioprotect 95% to 100% of irradiated mice, resulting long-term multilineage reconstitution. In this study, we examined the reconstitution potential of irradiated mice transplanted with purified Thy-1.1lo Lin-Sca-1+ BM cells. Donor-derived peripheral blood (PB) white blood cells were detected as early as day 9 or 10 when 100 to 1,000 Thy-1.1lo Lin-Sca-1+ cells were used, with minor dose-dependent differences. The reappearance of platelets by day 14 and thereafter was also seen at all HSC doses (100 to 1,000 cells), with a slight dose-dependence. All studied HSC doses also allowed RBC levels to recover, although at the 100 cell dose a delay in hematocrit recovery was observed at day 14. When irradiated mice were transplanted with 500 Thy-1.1lo Lin-Sca-1+ cells compared with 1 x 10(6) BM cells (the equivalent amount of cells that contain 500 Thy-1.1lo Lin-Sca-1+ cells as well as progenitor and mature cells), very little difference in the kinetics of recovery of PB, white blood cells, platelets, and hematocrit was observed. Surprisingly, even when 200 Thy1.1lo Lin-Sca- 1+ cells were mixed with 4 x 10(5) Sca-1- BM cells in a competitive repopulation assay, most of the early (days 11 and 14) PB myeloid cells were derived from the HSC genotype, indicating the superiority of the Thy-1.1lo Lin-Sca-1+ cells over Sca-1- cells even in the early phases of myeloid reconstitution. Within the Thy-1.1lo Lin-Sca-1+ population, the Rhodamine 123 (Rh123)hi subset dominates in PB myeloid reconstitution at 10 to 14 days, only to be overtaken by the Rh123lo subset at 3 weeks and thereafter. These findings indicate that HSCs can account for the early phase of hematopoietic recovery, as well as sustained hematopoiesis, and raise questions about the role of non-HSC BM populations in the setting of BMT.

scholarly journals Saccharomyces cerevisiae histone Chaperones FACT and Spt6 modulate Pol II and histone occupancy genome-wide

2018 ◽  
Author(s):  
Rakesh Pathak ◽  
Priyanka Singh ◽  
Sudha Ananthakrishnan ◽  
Sarah Adamczyk ◽  
Olivia Schimmel ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Critical Role ◽  
Histone Chaperones ◽  
Strongly Correlated ◽  
Pol Ii ◽  
Chromatin Remodelers ◽  
Coding Regions ◽  
Genome Wide ◽  
High Level

ABSTRACTHistone chaperones, chromatin remodelers, and histone modifying complexes play a critical role in alleviating the nucleosomal barrier. Here, we have examined the role of two highly conserved yeast (Saccharomyces cerevisiae) histone chaperones, FACT and Spt6, in regulating transcription and histone occupancy. We show that the H3 tail contributes to the recruitment of FACT to coding sequences in a manner dependent on acetylation. We found that deleting a H3 HAT Gcn5 or mutating lysines on the H3 tail impairs FACT recruitment at ADH1 and ARG1 genes. However, deleting the H4 tail or mutating the H4 lysines failed to dampen FACT occupancy in coding regions. Additionally, we show that FACT-depletion greatly reduces Pol II occupancy in the 5’ ends genome-wide. By contrast, Spt6-depletion led to reduction in Pol II occupancy towards the 3’ end, in a manner dependent on the gene-length. Severe transcription and histone eviction defects were also observed in a strain that was impaired for Spt6 recruitment (spt6Δ202) and depleted of FACT. Importantly, the severity of the defect strongly correlated with WT Pol II occupancies at these genes, indicating critical roles of Spt6 and Spt16 in promoting high-level transcription. Collectively, our study shows cooperation, as well as redundancy between chaperones, FACT and Spt6, in regulating transcription and chromatin in coding regions of transcribed genes.

Critical role of microglia in the inflammatory response after spinal injury

2015 ◽  
Vol 3 (3) ◽  
pp. 453-462
Author(s):  
Ya-Yun Shi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Responses ◽  
Spinal Injury ◽  
Critical Role ◽  
Cell Types ◽  
Inflammatory Factors ◽  
Cytokines And Chemokines ◽  
Cord Injury

Spinal cord injury induces a robust neuroinflammatory response that includes marked changes in the variety of endogenous CNS cell types specially microglia. In response to spinal injury, microglia undergo dramatic changes in cell morphology and promote inflammatory responses, which result in production of inflammatory factors and oxidative stress including reactive oxygen species. Further pro-inflammatory cytokines and chemokines are also rapidly up-regulated and likely contribute to microglial activation. This topic review will explore the current research on microglial responses to spinal injury and the recent progress in the pharmacologic and molecular targeting of microglia in spinal injury. Finally, we explore the argument for a positive versus negative role of microglia after spinal cord injury.

scholarly journals Role of exosomes and exosomal microRNAs in cancer

2020 ◽  
pp. FSO465 ◽  
Author(s):  
Nihat Dilsiz
Keyword(s):  
Critical Role ◽  
Cell Communication ◽  
Average Diameter ◽  
Cell Types ◽  
Specific Protein ◽  
Communication Process ◽  
Protein Biomarkers ◽  
Double Stranded Dna ◽  
Almost All

A growing body of evidence indicates that exosomes play a critical role in the cell–cell communication process. Exosomes are biological nanoparticles with an average diameter of 30–100 nm in size and are produced by almost all cell types in the human body; however, cancer cells contain higher concentrations of exosomes than healthy cells. They are released into all body fluids and contain double-stranded DNA (originated from nucleus and mitochondria), a variety of RNA species, and specific protein biomarkers that can be utilized as cancer biomarkers and therapeutic targets, and lipids. Therefore, the specific exosomes secreted by tumor cells could be used to predict the existence of the presence of a tumor in cancer patients. This review summarizes the role of exosomes in cancer development and their potential utility in the clinic.

The role of SLAM family receptors in immune cell signalingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Shawn S.-C. Li
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Types ◽  
Health And Disease ◽  
Slam Family ◽  
Different Cell Types ◽  
Selection Of

The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are expressed in a wide array of immune cells, including both T and B lymphocytes. By virtue of their ability to transduce tyrosine phosphorylation signals through the so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play an important part in regulating both innate and adaptive immune responses. The critical role of the SLAM immunoreceptors in mediating normal immune reactions was highlighted in recent findings that SAP, a SLAM-associated protein, modulates the activities of various immune cells through interactions with different members of the SLAM family expressed in these cells. Importantly, mutations or deletions of the sap gene in humans result in the X-linked lymphoproliferative syndrome. In this review, we summarize current knowledge and survey the latest developments in signal transduction events triggered by the activation of SLAM family receptors in different cell types.

scholarly journals Case not closed: the mystery of the origin of the carpel

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Beatriz Gonçalves
Keyword(s):  
Critical Role ◽  
Flowering Plants ◽  
Plant Evolution ◽  
Flowering Plant ◽  
Evolutionary Transition ◽  
Remarkable Feature ◽  
Stem Lineage ◽  
Long Time ◽  
Evolutionary Success ◽  
Closed Structure

AbstractThe carpel is a fascinating structure that plays a critical role in flowering plant reproduction and contributed greatly to the evolutionary success and diversification of flowering plants. The remarkable feature of the carpel is that it is a closed structure that envelopes the ovules and after fertilization develops into the fruit which protects, helps disperse, and supports seed development into a new plant. Nearly all plant-based foods are either derived from a flowering plant or are a direct product of the carpel. Given its importance it’s no surprise that plant and evolutionary biologists have been trying to explain the origin of the carpel for a long time. Before carpel evolution seeds were produced on open leaf-like structures that are exposed to the environment. When the carpel evolved in the stem lineage of flowering plants, seeds became protected within its closed structure. The evolutionary transition from that open precursor to the closed carpel remains one of the greatest mysteries of plant evolution. In recent years, we have begun to complete a picture of what the first carpels might have looked like. On the other hand, there are still many gaps in our understanding of what the precursor of the carpel looked like and what changes to its developmental mechanisms allowed for this evolutionary transition. This review aims to present an overview of existing theories of carpel evolution with a particular emphasis on those that account for the structures that preceded the carpel and/or present testable developmental hypotheses. In the second part insights from the development and evolution of diverse plant organs are gathered to build a developmental hypothesis for the evolutionary transition from a hypothesized laminar open structure to the closed structure of the carpel.

scholarly journals Codon arrangement modulates MHC-I peptides presentation

2020 ◽  
Author(s):  
Tariq Daouda ◽  
Maude Dumont-Lagacé ◽  
Albert Feghaly ◽  
Yahya Benslimane ◽  
Rébecca Panes ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Affinity ◽  
Cell Types ◽  
Amino Acid Sequences ◽  
Mhc I ◽  
Coding Regions ◽  
Synonymous Codons ◽  
Predictive Algorithms

AbstractMHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP coding regions, while excluding the MAP-coding codons per se. CAMAP predictions were significantly more accurate when using codon sequences than amino acid sequences. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules, and applied to several cell types and species. Combining MAP binding affinity, transcript expression level and CAMAP scores was particularly useful to ameliorate predictions of MAP derived from lowly expressed transcripts. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking MAP sequences (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome.

scholarly journals A disintegrin and metalloproteinase 17 regulates TNF and TNFR1 levels in inflammation and liver regeneration in mice

2013 ◽  
Vol 305 (1) ◽  
pp. G25-G34 ◽  
Author(s):  
Ryan S. McMahan ◽  
Kimberly J. Riehle ◽  
Nelson Fausto ◽  
Jean S. Campbell
Keyword(s):  
Liver Regeneration ◽  
Cell Types ◽  
Hepatocyte Proliferation ◽  
Growth Factor Signaling ◽  
Chemically Induced ◽  
Tnf Α ◽  
Essential Components ◽  
A Disintegrin And Metalloproteinase ◽  
Necrosis Factor

A disintegrin and metalloproteinase 17 (ADAM17), or tumor necrosis factor (TNF)-α-converting enzyme, is a key metalloproteinase and physiological convertase for a number of putative targets that play critical roles in cytokine and growth factor signaling. These interdependent pathways are essential components of the signaling network that links liver function with the compensatory growth that occurs during liver regeneration following 2/3 partial hepatectomy (PH) or chemically induced hepatotoxicity. Despite identification of many soluble factors needed for efficient liver regeneration, very little is known about how such ligands are regulated in the liver. To directly study the role of ADAM17 in the liver, we employed two cell-specific ADAM17 knockout (KO) mouse models. Using lipopolysaccharide (LPS) as a robust stimulus for TNF release, we found attenuated levels of circulating TNF in myeloid-specific ADAM17 KO mice (ADAM17 m-KO) and, unexpectedly, in mice with hepatocyte-specific ADAM17 deletion (ADAM17 h-KO), indicating that ADAM17 expression in both cell types plays a role in TNF shedding. After 2/3 PH, induction of TNF, TNFR1, and amphiregulin (AR) was significantly attenuated in ADAM17 h-KO mice, implicating ADAM17 as the primary sheddase for these factors in the liver. Surprisingly, the extent and timing of hepatocyte proliferation were not affected after PH or carbon tetrachloride injection in ADAM17 h-KO or ADAM17 m-KO mice. We conclude that ADAM17 regulates TNF, TNFR1, and AR in the liver, and its expression in both hepatocytes and myeloid cells is important for TNF regulation after LPS injury or 2/3 PH, but is not required for liver regeneration.

scholarly journals The Role of FAT10 in Alcoholic Hepatitis Pathogenesis

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 189
Author(s):  
Yue Jia ◽  
Ping Ji ◽  
Samuel W. French
Keyword(s):  
Alcoholic Hepatitis ◽  
Protein Quality ◽  
Chromosome Instability ◽  
Critical Role ◽  
Cell Types ◽  
Cell Protein ◽  
Milk Thistle ◽  
Aggregation Formation ◽  
Derivatives Of

FAT10 expression is highly up-regulated by pro-inflammatory cytokines IFNγ and TNFα in all cell types and tissues. Increased FAT10 expression may induce increasing mitotic non-disjunction and chromosome instability, leading to tumorigenesis. In this review, we summarized others’ and our work on FAT10 expression in liver biopsy samples from patients with alcoholic hepatitis (AH). FAT10 is essential to maintain the function of liver cell protein quality control and Mallory–Denk body (MDB) formation. FAT10 overexpression in AH leads to balloon degeneration and MDB aggregation formation, all of which is prevented in fat10-/- mice. FAT10 causes the proteins’ accumulation, overexpression, and forming MDBs through modulating 26s proteasome’s proteases. The pathway that increases FAT10 expression includes TNFα/IFNγ and the interferon sequence response element (ISRE), followed by NFκB and STAT3, which were all up-regulated in AH. FAT10 was only reported in human and mouse specimens but plays critical role for the development of alcoholic hepatitis. Flavanone derivatives of milk thistle inhibit TNFα/IFNγ, NFκB, and STAT3, then inhibit the expression of FAT10. NFκB is the key nodal hub of the IFNα/TNFα-response genes. Studies on Silibinin and other milk thistle derivatives to treat AH confirms that overexpressed FAT10 is the major key molecule in these networks.

scholarly journals Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis

2019 ◽  
Vol 316 (6) ◽  
pp. H1528-H1537 ◽  
Author(s):  
Hyehun Choi ◽  
Ryan J. Stark ◽  
Benjamin S. Raja ◽  
Anna Dikalova ◽  
Fred S. Lamb
Keyword(s):  
Tumor Necrosis Factor ◽  
Nadph Oxidase ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Receptor Endocytosis ◽  
Signaling Complex ◽  
Essential Components ◽  
Nadph Oxidase 1 ◽  
Necrosis Factor

Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine that is closely linked to the development of cardiovascular disease. TNFα activates NADPH oxidase 1 (Nox1) and reactive oxygen species (ROS), including superoxide (O2·−), production extracellularly is required for subsequent signaling in vascular smooth muscle cells (VSMCs). Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that is activated by oxidation of associated thioredoxin. The role of ASK1 in Nox1-mediated signaling by TNFα is poorly defined. We hypothesized that ASK1 is required for TNFα receptor endocytosis and subsequent inflammatory TNFα signaling. We employed a knockdown strategy to explore the role of ASK1 in TNFα signaling in VSMCs. siRNA targeting ASK1 had no effect on TNFα-induced extracellular O2·− production. However, siASK1 inhibited receptor endocytosis as well as phosphorylation of two endocytosis-related proteins, dynamin1 and caveolin1. Intracellular O2·− production was subsequently reduced, as were other inflammatory signaling steps including NF-κB activation, IL-6 production, inducible nitric oxide synthase and VCAM expression, and VSMC proliferation. Prolonged exposure to TNFα (24 h) increased tumor necrosis factor receptor (TNFR) subtype 1 and 2 expression, and these effects were also attenuated by siASK1. ASK1 coimmunoprecipitated with both Nox1 and the leucine rich repeat containing 8A anion channel, two essential components of the TNFR1 signaling complex. Activation of ASK1 by autophosphorylation at Thr845 occurs following thioredoxin dissociation, and this requires the presence of Nox1. Thus, Nox1 is part of the multiprotein ASK1 signaling complex. In response to TNFα, ASK1 is activated by Nox1-derived oxidants, and this plays a critical role in translating these ROS into a physiologic response in VSMCs. NEW & NOTEWORTHY Apoptosis signal-regulating kinase 1 (ASK1) drives dynamin1 and caveolin1 phosphorylation and TNFα receptor endocytosis. ASK1 modulates TNFα-induced NF-κB activation, survival, and proliferation. ASK1 and NADPH oxidase 1 (Nox1) physically associate in a multiprotein signaling complex. Nox1 is required for TNFα-induced ASK1 activation.

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